UTILIZATION OF GROWTH CURVES FOR OPTIMIZATION OF TYPE 2 DIABETES TREATMENT

Abstract

A system is provided herein for stimulating an anatomical element of a patient. For example, the system may include a device configured to generate a current (e.g., implantable pulse generator), a first electrode device configured to apply the current to the anatomical element, and a second electrode device configured to record one or more response measurements associated with applying the current to the anatomical element. In some examples, the one or more response measurements may be used to generate growth curves associated with applying the current to the anatomical element, where the growth curves can be used to adjust one or more parameters of the current. Additionally, the one or more response measurements may include an evoked compound action potential (eCAP) measurement, an electromyography (EMG) measurement, a glucose level measurement, or a combination thereof.

Description

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No. 63/339,160, filed on May 6, 2022, entitled “Utilization of Growth Curves for Optimization of Type 2 Diabetes Treatment”, and further identified as Attorney Docket No. A0008265US02 (10259-211-14P); U.S. Provisional Application No. 63/338,794, filed on May 5, 2022, entitled “Systems and Methods for Stimulating an Anatomical Element Using an Electrode Device”, and further identified as Attorney Docket No. A0008247US01 (10259-211-1P); U.S. Provisional Application No. 63/339,049, filed on May 6, 2022, entitled “Systems and Methods for Mechanically Blocking a Nerve”, and further identified as Attorney Docket No. A0008250US01 (10259-211-2P); U.S. Provisional Application No. 63/338,806, filed on May 5, 2022, entitled “Systems and Methods for Wirelessly Stimulating or Blocking at Least One Nerve”, and further identified as Attorney Docket No. A0008251US01 (10259-211-3P); U.S. Provisional Application No. 63/339,101, filed on May 6, 2022, entitled “Neuromodulation Techniques to Create a Nerve Blockage with a Combination Stimulation/Block Therapy for Glycemic Control”, and further identified as Attorney Docket No. A0008252US01 (10259-211-4P); U.S. Provisional Application No. 63/339,136, filed on May 6, 2022, entitled “Neuromodulation for Treatment of Neonatal Chronic Hyperinsulinism”, and further identified as Attorney Docket No. A0008253US01 (10259-211-5P); U.S. Provisional Application No. 63/342,945, filed on May 17, 2022, entitled “Neuromodulation Techniques for Treatment of Hypoglycemia”, and further identified as Attorney Docket No. A0008255US01 (10259-211-6P); U.S. Provisional Application No. 63/342,998, filed on May 17, 2022, entitled “Closed-Loop Feedback and Treatment”, and further identified as Attorney Docket No. A0008258US01 (10259-211-7P); U.S. Provisional Application No. 63/338,817, filed on May 5, 2022, entitled “Systems and Methods for Monitoring and Controlling an Implantable Pulse Generator”, and further identified as Attorney Docket No. A0008259US01 (10259-211-8P); U.S. Provisional Application No. 63/339,024, filed on May 6, 2022, entitled “Programming and Calibration of Closed-Loop Vagal Nerve Stimulation Device”, and further identified as Attorney Docket No. A0008260US01 (10259-211-9P); U.S. Provisional Application No. 63/339,304, filed on May 6, 2022, entitled “Systems and Methods for Stimulating or Blocking a Nerve Using an Electrode Device with a Sutureless Closure”, and further identified as Attorney Docket No. A0008262US01 (10259-211-11P); U.S. Provisional Application No. 63/339,154, filed on May 6, 2022, entitled “Personalized Machine Learning Algorithm for Stimulation/Block Therapy for Treatment of Type 2 Diabetes”, and further identified as Attorney Docket No. A0008263US01 (10259-211-12P); and U.S. Provisional Application No. 63/342,967, filed on May 17, 2022, entitled “Patient User Interface for a Stimulation/Block Therapy for Treatment of Type 2 Diabetes”, and further identified as Attorney Docket No. A0008264US01 (10259-211-13P), all of which applications are incorporated herein by reference in their entireties.

BACKGROUND

The present disclosure is generally directed to therapeutic neuromodulation and relates more particularly to a stimulation/block therapy to affect glycemic control of a patient.

Diabetes represents a large and growing global health issue with estimates of over 537 million patients worldwide having been diagnosed with type 2 diabetes and estimates of 6.7 million annual deaths related to complications of diabetes. Despite different types of treatments being developed and utilized (e.g., medication, surgery, diet, etc.), type 2 diabetes remains challenging to effectively treat. Type 2 patients must frequently contend with keeping their blood sugar levels in a desirable glycemic range. Prolonged deviations can lead to long term complications such as retinopathy, nephropathy (e.g., kidney damage), cardiovascular disease, etc. Because treatment for diabetes is self-managed by the patient on a day-to-day basis (e.g., the patients self-inject the insulin), compliance or adherence with treatments can be problematic.

BRIEF SUMMARY

Example aspects of the present disclosure include:

A system for stimulating an anatomical element of a patient, comprising: an implantable pulse generator configured to generate a current; a first electrode device electrically coupled to the implantable pulse generator, the first electrode device comprising a first plurality of electrodes configured for placement on or around the anatomical element of the patient; a second electrode device electrically coupled to the implantable pulse generator, the second electrode device comprising a second plurality of electrodes configured for placement on or around the anatomical element of the patient; a processor; and a memory storing data for processing by the processor, the data, when processed, causes the processor to: transmit instructions to the implantable pulse generator to apply the current to the anatomical element of the patient via the first electrode device, wherein the current is applied using a set of parameters that correspond to an expected physiological response; receive a response measurement recorded via the second electrode device based at least in part on applying the current via the first electrode device; and adjust one or more parameters of the set of parameters for the implantable pulse generator to apply the current based at least in part on the response measurement being different than the expected physiological response.

Any of the aspects herein, wherein the data stored in the memory that, when processed causes the processor to adjust the one or more parameters causes the system to: adjust an amplitude, frequency, charge density, or a combination thereof for the current.

Any of the aspects herein, wherein the response measurement comprises an evoked compound action potential (eCAP) measurement, an electromyography (EMG) measurement, a glucose level measurement, or a combination thereof.

Any of the aspects herein, wherein the memory stores further data for processing by the processor that, when processed, causes the processor to: receive a plurality of response measurements recorded via the second electrode device over a period of time, the period of time coinciding at least with a duration of the current being applied to the anatomical element; and generate one or more growth curves based at least in part on the plurality of response measurements, wherein the one or more parameters are adjusted based at least in part on the one or more growth curves.

Any of the aspects herein, wherein the memory stores further data for processing by the processor that, when processed, causes the processor to: receive values for one or more of the set of parameters used to apply the current to the anatomical element, the values recorded via the second electrode device at each instance that a response measurement of the plurality of response measurements is recorded.

Any of the aspects herein, wherein a maximum response measurement of the plurality of response measurements corresponds to optimal values for the set of parameters recorded at a same time instance that the maximum response measurement is recorded, the optimal values for the set of parameters being optimal for applying the current to the anatomical element to achieve a desired glycemic response in the patient.

Any of the aspects herein, wherein the one or more parameters are adjusted based at least in part on the optimal values.

Any of the aspects herein, wherein the response measurement being different than the expected physiological response indicates an operational issue.

Any of the aspects herein, wherein the operational issue comprises a fibrous growth on the anatomical element that affects applying the current via the first electrode, the first electrode and/or the second electrode not being properly placed on the anatomical element, the anatomical element being too large for proper placement of the first electrode, or a combination thereof.

Any of the aspects herein, wherein the current being applied to the anatomical element reduces a glycemic response in the patient.

Any of the aspects herein, wherein the anatomical element comprises a celiac vagal trunk, a hepatic vagal trunk, or both of the patient.

A system for stimulating an anatomical element of a patient, comprising: an implantable pulse generator configured to generate a current; a first electrode device comprising: a first body and a first plurality of electrodes disposed on the first body and configured to apply the current to the anatomical element; a second electrode device comprising: a second body and a second plurality of electrodes disposed on the second body and configured to record measurements corresponding to the current when the current is applied to the anatomical element; a processor; and a memory storing data for processing by the processor, the data, when processed, causes the processor to: transmit instructions to the implantable pulse generator to apply the current to the anatomical element of the patient via the first electrode device, wherein the current is applied using a set of parameters that correspond to an expected physiological response; receive a response measurement recorded via the second electrode device based at least in part on applying the current via the first electrode device; and adjust one or more parameters of the set of parameters for the implantable pulse generator to apply the current based at least in part on the response measurement being different than the expected physiological response.

Any of the aspects herein, wherein the data stored in the memory that, when processed causes the processor to adjust the one or more parameters causes the system to: adjust an amplitude, frequency, charge density, or a combination thereof for the current.

Any of the aspects herein, wherein the response measurement comprises an evoked compound action potential (eCAP) measurement, an electromyography (EMG) measurement, a glucose level measurement, or a combination thereof.

Any of the aspects herein, wherein the memory stores further data for processing by the processor that, when processed, causes the processor to: receive a plurality of response measurements recorded via the second electrode device over a period of time, the period of time coinciding at least with a duration of the current being applied to the anatomical element; and generate one or more growth curves based at least in part on the plurality of response measurements, wherein the one or more parameters are adjusted based at least in part on the one or more growth curves.

Any of the aspects herein, wherein the memory stores further data for processing by the processor that, when processed, causes the processor to: receive values for one or more of the set of parameters used to apply the current to the anatomical element, the values recorded via the second electrode device at each instance that a response measurement of the plurality of response measurements is recorded.

Any of the aspects herein, wherein a maximum response measurement of the plurality of response measurements corresponds to optimal values for the set of parameters recorded at a same time instance that the maximum response measurement is recorded, the optimal values for the set of parameters being optimal for applying the current to the anatomical element to achieve a desired glycemic response in the patient.

Any of the aspects herein, wherein the one or more parameters are adjusted based at least in part on the optimal values.

A system for stimulating an anatomical element of a patient, comprising: an implantable pulse generator configured to generate a current; a first electrode device electrically coupled to the implantable pulse generator, the first electrode device comprising a first plurality of electrodes for placement on or around the anatomical element of the patient, wherein the first plurality of electrodes is configured to apply the current to the anatomical element; and a second electrode device electrically coupled to the implantable pulse generator, the second electrode device comprising a second plurality of electrodes for placement on or around the anatomical element of the patient, wherein the second plurality of electrodes is configured to record measurements corresponding to the current when the current is applied to the anatomical element.

Any of the aspects herein, wherein the current being applied to the anatomical element via the first electrode device reduces a glycemic response in the patient.

Any aspect in combination with any one or more other aspects.

Any one or more of the features disclosed herein.

Any one or more of the features as substantially disclosed herein.

Any one or more of the features as substantially disclosed herein in combination with any one or more other features as substantially disclosed herein.

Any one of the aspects/features/embodiments in combination with any one or more other aspects/features/embodiments.

Use of any one or more of the aspects or features as disclosed herein.

It is to be appreciated that any feature described herein can be claimed in combination with any other feature(s) as described herein, regardless of whether the features come from the same described embodiment.

The details of one or more aspects of the disclosure are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the techniques described in this disclosure will be apparent from the description and drawings, and from the claims.

The phrases “at least one”, “one or more”, and “and/or” are open-ended expressions that are both conjunctive and disjunctive in operation. For example, each of the expressions “at least one of A, B and C”, “at least one of A, B, or C”, “one or more of A, B, and C”, “one or more of A, B, or C” and “A, B, and/or C” means A alone, B alone, C alone, A and B together, A and C together, B and C together, or A, B and C together. When each one of A, B, and C in the above expressions refers to an element, such as X, Y, and Z, or class of elements, such as X1-Xn, Y1-Ym, and Z1-Zo, the phrase is intended to refer to a single element selected from X, Y, and Z, a combination of elements selected from the same class (e.g., X1 and X2) as well as a combination of elements selected from two or more classes (e.g., Y1 and Zo).

The term “a” or “an” entity refers to one or more of that entity. As such, the terms “a” (or “an”), “one or more” and “at least one” can be used interchangeably herein. It is also to be noted that the terms “comprising”, “including”, and “having” can be used interchangeably.

The preceding is a simplified summary of the disclosure to provide an understanding of some aspects of the disclosure. This summary is neither an extensive nor exhaustive overview of the disclosure and its various aspects, embodiments, and configurations. It is intended neither to identify key or critical elements of the disclosure nor to delineate the scope of the disclosure but to present selected concepts of the disclosure in a simplified form as an introduction to the more detailed description presented below. As will be appreciated, other aspects, embodiments, and configurations of the disclosure are possible utilizing, alone or in combination, one or more of the features set forth above or described in detail below.

Numerous additional features and advantages of the present disclosure will become apparent to those skilled in the art upon consideration of the embodiment descriptions provided hereinbelow.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

The accompanying drawings are incorporated into and form a part of the specification to illustrate several examples of the present disclosure. These drawings, together with the description, explain the principles of the disclosure. The drawings simply illustrate preferred and alternative examples of how the disclosure can be made and used and are not to be construed as limiting the disclosure to only the illustrated and described examples. Further features and advantages will become apparent from the following, more detailed, description of the various aspects, embodiments, and configurations of the disclosure, as illustrated by the drawings referenced below.

FIG. 1 is a diagram of a system according to at least one embodiment of the present disclosure;

FIG. 2 is a system according to at least one embodiment of the present disclosure;

FIG. 3 is a block diagram of a system according to at least one embodiment of the present disclosure;

FIG. 4 is a flowchart according to at least one embodiment of the present disclosure; and

FIG. 5 is a flowchart according to at least one embodiment of the present disclosure.

DETAILED DESCRIPTION

It should be understood that various aspects disclosed herein may be combined in different combinations than the combinations specifically presented in the description and accompanying drawings. It should also be understood that, depending on the example or embodiment, certain acts or events of any of the processes or methods described herein may be performed in a different sequence, and/or may be added, merged, or left out altogether (e.g., all described acts or events may not be necessary to carry out the disclosed techniques according to different embodiments of the present disclosure). In addition, while certain aspects of this disclosure are described as being performed by a single module or unit for purposes of clarity, it should be understood that the techniques of this disclosure may be performed by a combination of units or modules associated with, for example, a computing device and/or a medical device.

In one or more examples, the described methods, processes, and techniques may be implemented in hardware, software, firmware, or any combination thereof. If implemented in software, the functions may be stored as one or more instructions or code on a computer-readable medium and executed by a hardware-based processing unit. Alternatively or additionally, functions may be implemented using machine learning models, neural networks, artificial neural networks, or combinations thereof (alone or in combination with instructions). Computer-readable media may include non-transitory computer-readable media, which corresponds to a tangible medium such as data storage media (e.g., random-access memory (RAM), read-only memory (ROM), electrically erasable programmable ROM (EEPROM), flash memory, or any other medium that can be used to store desired program code in the form of instructions or data structures and that can be accessed by a computer).

Instructions may be executed by one or more processors, such as one or more digital signal processors (DSPs), general purpose microprocessors (e.g., Intel Core i3, i5, i7, or i9 processors; Intel Celeron processors; Intel Xeon processors; Intel Pentium processors; AMD Ryzen processors; AMD Athlon processors; AMD Phenom processors; Apple A10 or 10X Fusion processors; Apple A11, A12, A12X, A12Z, or A13 Bionic processors; or any other general purpose microprocessors), graphics processing units (e.g., Nvidia GeForce RTX 2000-series processors, Nvidia GeForce RTX 3000-series processors, AMD Radeon RX 5000-series processors, AMD Radeon RX 6000-series processors, or any other graphics processing units), application specific integrated circuits (ASICs), field programmable logic arrays (FPGAs), or other equivalent integrated or discrete logic circuitry. Accordingly, the term “processor” as used herein may refer to any of the foregoing structure or any other physical structure suitable for implementation of the described techniques. Also, the techniques could be fully implemented in one or more circuits or logic elements. The processors listed herein are not intended to be an exhaustive list of all possible processors that can be used for implementation of the described techniques, and any future iterations of such chips, technologies, or processors may be used to implement the techniques and embodiments of the present disclosure as described herein.

Before any embodiments of the disclosure are explained in detail, it is to be understood that the disclosure is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the drawings. The disclosure is capable of other embodiments and of being practiced or of being carried out in various ways. Also, it is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of “including,” “comprising,” or “having” and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items. Further, the present disclosure may use examples to illustrate one or more aspects thereof. Unless explicitly stated otherwise, the use or listing of one or more examples (which may be denoted by “for example,” “by way of example,” “e.g.,” “such as,” or similar language) is not intended to and does not limit the scope of the present disclosure.

Vagus nerve stimulation (VNS) is a technology that has been developed to treat different disorders or ailments of a patient, such as epilepsy and depression. In some examples, VNS involves placing a device in or on a patient's body that uses electrical impulses to stimulate the vagus nerve. For example, the device may be usually placed under the skin of the patient, where a wire (e.g., lead) and/or electrode connects the device to the vagus nerve. Once the device is activated, the device sends signals through the vagus nerve to the patient's brainstem (e.g., or different target area in the patient, such as other organs of the patient), transmitting information to their brain. For example, with VNS, the device may be configured to send regular, mild pulses of electrical energy to the brain via the vagus nerve. In some examples, the device may be referred to as an implantable pulse generator. An implantable vagus nerve stimulator has been approved to treat epilepsy and depression in qualifying patients.

The vagus nerve (e.g., also called the pneumogastric nerve, vagal nerve, the cranial nerve X, etc.) is responsible for various internal organ functions of a patient, including digestion, heart rate, breathing, cardiovascular activity, and reflex actions (e.g., coughing, sneezing, swallowing, and vomiting). Most patients may have one vagus nerve on each side of their body, with numerous branches running from their brainstem through their neck, chest, and abdomen down to part of their colon. The vagus nerve plays a role in many bodily functions and may form a link between different areas of the patient, such as the brain and the gut. The vagus nerve is a critical nerve for supplying parasympathetic information to the visceral organs of the respiratory, digestive, and urinary systems. Additionally, the vagus nerve is important in the control of heart rate, bronchoconstriction, and digestive processes. In some cases, the vagus nerve may be considered a mixed nerve based on including both afferent (sensory) fibers and efferent (motor) fibers. As such, based on including the two types of fibers, the vagus nerve may be responsible for carrying motor signals to organs for innervating the organs (e.g., via the efferent fibers), as well as carrying sensory information from the organs back to the brain (e.g., via the afferent fibers).

The vagus nerve has a number of different functions. Four key functions of the vagus nerve are carrying sensory signals, carrying special sensory signals, providing motor functions, and assisting in parasympathetic functions. For example, the sensory signals carried by the vagus nerve may include signaling between the brain and the throat, heart, lungs, and abdomen. The special sensory signals carried by the vagus nerve may provide signaling of special senses in the patient, such as the taste sensation behind the tongue. Additionally, the vagus nerve may enable certain motor functions of the patient, such as providing movement functions for muscles in the neck responsible for swallowing and speech. The parasympathetic functions provided by the vagus nerve may include digestive tract, respiration, and heart rate functioning. In some cases, the nervous system can be divided into two areas: sympathetic and parasympathetic. The sympathetic side increases alertness, energy, blood pressure, heart rate, and breathing rate. The parasympathetic side, which the vagus nerve is heavily involved in, decreases alertness, blood pressure, and heart rate, and helps with calmness, relaxation, and digestion.

VNS is considered a type of neuromodulation (e.g., a technology that acts directly upon nerves of a patient, such as the alteration, or “modulation,” of nerve activity by delivering electrical impulses or pharmaceutical agents directly to a target area). For example, as described above, VNS may include using a device (e.g., implanted in a patient or attached to the patient) that is configured to send regular, mild pulses of electrical energy to a target area of the patient (e.g., brainstem, organ, etc.) via the vagus nerve. The electrical pulses or impulses may affect how that target area of the patient functions to potentially treat different disorders or ailments of a patient.

In some examples, for epileptic patients that suffer from seizures, VNS may change how brain cells work by applying electrical stimulation to certain areas involved in seizures. For example, research has shown that VNS may help control seizures by increasing blood flow in key areas, raising levels of some brain substances (e.g., neurotransmitters) important to control seizures, changing electroencephalogram (EEG) patterns during a seizure, etc. As an example, an epileptic patient's heart rate may increase during a seizure or epileptic episode, so the VNS device may be programmed to send stimulation to the vagus nerve regular intervals and when periods of increased heart rate are seen, where applying stimulation at those times of increased heart rate may help stop seizures. Additionally or alternatively, depression has been tied to an imbalance in certain brain chemicals (e.g., neurotransmitters), so VNS is believed to assist in treating patients diagnosed with depression by using electricity (e.g., electrical pulses/impulses) to influence the production of those brain chemicals.

Diabetes represents a large and growing global health issue with estimates of over 537 million patients worldwide having been diagnosed with type 2 diabetes and estimates of 6.7 million annual deaths related to complications of diabetes. Despite different types of treatments being developed and utilized (e.g., medication, surgery, diet, etc.), type 2 diabetes remains challenging to effectively treat. Type 2 patients must frequently contend with keeping their blood sugar levels in a desirable glycemic range. Prolonged deviations can lead to long term complications such as retinopathy, nephropathy (e.g., kidney damage), cardiovascular disease, etc. Because treatment for diabetes is self-managed by the patient on a day-to-day basis (e.g., the patients self-inject the insulin), compliance or adherence with treatments can be problematic. Additionally, in a financial sense, global expenditures for type 2 diabetes treatments, preventive measures, and resulting consequences are estimated at about $966 billion per year. Compounding this issue of high global expenditures is the increasing price of insulin.

As described herein, a neuromodulation technique is provided for glycemic control (e.g., as a treatment for diabetes) using a stimulation/block therapy (e.g., type of VNS). For example, the neuromodulation technique may generally include using a device (e.g., including at least an implantable pulse generator) to provide electrical stimulation (e.g., electrical pulses/impulses) on one or more trunks of the vagus nerve (e.g., vagal trunks) to mute a glycemic response for patients with diabetes. The “patient” as used herein may refer to Homo sapiens or any other living being that has a vagus nerve.

In some examples, the device may provide stimulation/blocking of the celiac and hepatic vagal trunks (e.g., using the device) for the purposes of glycemic control. For example, the anterior sub diaphragmatic vagal trunk at the hepatic branching point of the vagus nerve may be electrically blocked (e.g., down-regulated) by delivering a high frequency stimulation (e.g., of about 5 kilohertz (kHz) or in a range between 1 kHz to 50 kHz). Additionally or alternatively, the posterior sub diaphragmatic vagal trunk at the celiac branching point of the vagus nerve may be electrically stimulated (e.g., up-regulated) by delivering a low frequency stimulation (e.g., a square wave at 1 Hz or within a range from 0.1 to 20 Hz). In some examples, the electrical blocking and/or electrical stimulating of the respective vagal trunks may be performed by using one or more cuff electrodes (e.g., of the device) placed on the corresponding vagal trunks (e.g., sutured or otherwise held in place). The desired response by providing the stimulation/block therapy is a muting of the glycemic response of a patient. In some examples, muting of the glycemic response may refer to a lower post prandial peak of the glycemic response as compared to a peak without the stimulation/block therapy being applied.

Using the stimulation/block therapy to achieve a muting of the glycemic response is advantageous for those with type 2 diabetes where the postprandial glycemic response (e.g., occurring after a meal) can be very high. For example, some patients with type 2 diabetes may have high blood sugar levels (e.g., glucose levels) after eating a meal based on their reduced or lack of insulin production (e.g., normal insulin production in the body lowers blood sugar levels postprandially by promoting absorption of glucose from the blood into different cells). Additionally or alternatively, patients diagnosed with type 2 diabetes may generally have high glycemic levels at different points of the day (e.g., not necessarily postprandially or immediately after a meal). Over time, the effect of high glycemic values can have a detrimental effect on one's health, leading to neuropathy, retinopathy, and other ailments. Accordingly, by using the stimulation/block therapy provided herein, a high glycemic response experienced by type 2 diabetes patients may be muted (e.g., the glycemic response is reduced, particularly post prandially). Additionally, the therapy aims to improve insulin sensitivity by blocking hepatic glucose production and also by stimulating pancreatic insulin production needed for glycemic control, where the lack of insulin sensitivity can potentially lead to an imbalance in glycemic control and consequent systemic complications in patients with type 2 diabetes. In some examples, the therapy may also improve fasting hyperglycemia, which can be commonly seen in patients with type 2 diabetes.

In some examples, a system may be provided that uses growth curves for the optimization of stimulation frequency and amplitude for the stimulation/block therapy described herein. A growth curve refers to the iterative stimulation and frequency and amplitude parameters that evoke response in the nerve or response in the body (e.g., the evoked responses can be electrical compound action potentials from a stimulated nerve, electromyography (EMG) from closer muscles, or glucose monitor changes). For example, characterization of the vagus nerve using growth curves may help guide calibration and optimization of vagal nerve stimulation therapy for the treatment of diabetes. In some examples, stimulus evoked compound action potentials (eCAPS) may provide information about fiber engagement for the stimulation/block therapy (e.g., how successfully the therapy is applied to activate nerve fibers of interest in the vagus nerve) and, thus, may inform how much stimulus to provide with the stimulation/block therapy (e.g., indicate an amplitude and/or frequency for applying the current). The optimization may enable efficient battery usage for the device that is configured to generate the current that is to be applied to the anatomical element of the patient (e.g., an implantable pulse generator, implantable neurostimulator, etc.) and may avoid possible risk of damage to nerves in the patient by saturation of input levels. The optimization of such stimulation/block therapy may be important during insertion of the device (e.g., implanting the device) and at periodic follow up office visits for the patient.

The setup to perform such a calibration for determining optimal parameters for applying the current to the anatomical element to achieve a desired glycemic response in the patient may generally involve a stimulation electrode (e.g., a first electrode device) configured to be placed on a nerve fiber of the vagus nerve and a recording electrode (e.g., a second electrode device) configured to be placed downstream on the same nerve fiber. The setup of the stimulation electrode and the recording electrode is described in greater detail with reference to FIG. 2. A resulting measurement captured by the recording electrode when the stimulation electrode applies the current to the nerve fiber may represent an eCAP measurement corresponding to the current applied to the nerve fiber, an EMG measurement (e.g., indicating muscle activity that occurs based on applying the current to a nerve fiber near the corresponding muscle(s)), glucose level measurement changes (e.g., as observed by a glucose sensor, such as a continuous glucose monitor disposed in or on the patient). Additionally, parameters used by the stimulation electrode when applying the current to the nerve fiber (e.g., frequency, amplitude, etc.) may be captured with the resulting measurement.

In some examples, a maximum of the resulting measurement captured by the recording electrode when the stimulation electrode applies the current to the nerve fiber (e.g., a peak eCAP measurement, a peak EMG measurement, a peak glucose level change, etc.) may be concomitant (e.g., coinciding or occurring together) with optimal parameters for applying the current to the nerve fiber (e.g., an optimal stimulus amplitude and frequency). Accordingly, for subsequent implementations of the stimulation/block therapy, the optimal parameters may be used for applying the current to the anatomical element of the patient to achieve a desired glycemic response in the patient and/or to generate a particular resulting measurement captured by the recording electrode when the stimulation electrode applies the current to the nerve fiber.

Embodiments of the present disclosure provide technical solutions to one or more of the problems of (1) controlling a glycemic response of a patient, (2) determining optimal parameters for applying a stimulation/block therapy, and (3) troubleshooting possible operational issues for the stimulation/block therapy. For example, the present disclosure may provide a mechanism to measure an amount of therapy (e.g., frequency, amplitude, etc.) that is needed to be applied to an anatomical element of a patient to achieve a desired glycemic response in the patient based on applying a signal (e.g., current) on a nerve (e.g., via a first electrode device) and observing the signal further down the same nerve (e.g., via a second electrode device) that should have expected values or characteristics. Accordingly, if the observed signal has different values than those which are expected, one or more parameters of the signal may be adjusted to optimally achieve the desired glycemic response (e.g., adjust charge density, amplitude, frequency if needed). In some examples, one or more factors may exist that affect the signal not having the expected values, such as a size of the nerve being too large to properly place the electrode device(s), the electrode devices not being placed accurately, fibrous growths on the nerve, etc. As such, if the observed signal has different values than those which are expected, one of these factors may be present and then mitigated to achieve the desired glycemic response (e.g., provide troubleshooting for determining one of the factors is present).

In some examples, the present disclosure may be utilized for performing a calibration procedure. Additionally or alternatively, the present disclosure may be utilized based on a detected issue with the stimulation/block therapy (e.g., the stimulation/block therapy is not performing as expected or is not producing expected results for the patient). Accordingly, the present disclosure may be used to determine why the stimulation/block therapy is performing incorrectly, to determine optimal parameters for the stimulation/block therapy, to calibrate the stimulation/block therapy, or a combination thereof.

Turning to FIG. 1, a diagram of a system 100 according to at least one embodiment of the present disclosure is shown. The system 100 may be used to provide glycemic control for a patient and/or carry out one or more other aspects of one or more of the methods disclosed herein. For example, the system 100 may include at least a device 104 that is capable of providing a stimulation/blocking therapy that mutes a glycemic response for patients with diabetes. In some examples, the device 104 may be referred to as an implantable pulse generator, an implantable neurostimulator, or another type of device not explicitly listed or described herein. Additionally, the system 100 may include one or more wires 108 (e.g., leads) that provide a connection between the device 104 and nerves of the patient for enabling the stimulation/blocking therapy.

As described previously, neuromodulation techniques (e.g., technologies that act directly upon nerves of a patient, such as the alteration, or “modulation,” of nerve activity by delivering electrical impulses or localized pharmaceutical agents directly to a target area) may be used for assisting in treatments for different diseases, disorders, or ailments of a patient, such as epilepsy and depression. Accordingly, as described herein, the neuromodulation techniques may be used for muting a glycemic response in the patient to assist in the treatment of diabetes for the patient. For example, the device 104 may provide electrical stimulation to one or more trunks of the vagus nerve of the patient (e.g., via the one or more wires 108) to provide the stimulation/blocking therapy for supporting glycemic control in the patient.

In some examples, the one or more wires 108 may include at least a first wire 108A and a second wire 108B connected to respective vagal trunks (e.g., different trunks of the vagus nerve). As described previously, most patients have one vagus nerve on each side of their body, running from their brainstem through their neck, chest, and abdomen down to part of their colon. The vagus nerve plays a role in many bodily functions and may form a link between different areas of the patient, such as the brain and the gut. For example, the vagus nerve is responsible for various internal organ functions of a patient, including digestion, heart rate, breathing, cardiovascular activity, and reflex actions (e.g., coughing, sneezing, swallowing, and vomiting).

Accordingly, the first wire 108A may be connected to a first vagal trunk of the patient (e.g., the anterior sub diaphragmatic vagal trunk at the hepatic branching point of the vagus nerve) to provide an electrical blocking signal (e.g., a down-regulating signal) from the device 104 to that first vagal trunk (e.g., by delivering a high frequency stimulation, such as a given waveform at about 5 kHz). Additionally or alternatively, the second wire 108B may be connected to a second vagal trunk of the patient (e.g., the posterior sub diaphragmatic vagal trunk at the celiac branching point of the vagus nerve) to provide an electrical stimulation signal (e.g., an up-regulating signal) from the device 104 to that second vagal trunk (e.g., by delivering a low frequency stimulation, such as a square wave or other waveform at 1 Hz). By providing the electrical blocking signal and the electrical stimulation signal to the respective vagal trunks, the system 100 may provide a muting of the glycemic response of the patient when the stimulation/blocking therapy is applied. For example, muting of the glycemic response may refer to a lower post prandial peak of the glycemic response as compared to a peak without the stimulation/block therapy being applied.

In some examples, the vagal trunks to which the wires 108 are connected may be connected to or otherwise in the vicinity of one or more organs of the patient, such that the blocking/stimulation signals provided to the respective vagal trunks by the wires 108 and the device 104 are delivered to the one or more organs. For example, the first vagal trunk (e.g., to which the first wire 108A is connected) may be connected to a first organ 112 of the patient, and the second vagal trunk (e.g., to which the second wire 108B is connected) may be connected to a second organ 116. Additionally or alternatively, while the respective vagal trunks are shown as being connected to the corresponding organs of the patient as described, the vagal trunks to which the wires 108 are connected may be connected to the other organ (e.g., the first vagal trunk is connected to the second organ 116 and the second vagal trunk is connected to the first organ 112) or may be connected to different organs of the patient. In some examples, the first organ 112 may represent a liver of the patient, and the second organ 116 may represent a pancreas of the patient. In such examples, the blocking/stimulation signals provided by the wires 108 and the device 104 may be delivered to the liver and/or pancreas of the patient to mute a glycemic response of the patient as described herein.

In some examples, the wires 108 may provide the electrical signals to the respective vagal trunks via electrodes of an electrode device (e.g., cuff electrodes) that are connected to the vagal trunks (e.g., sutured in place, wrapped around the nerves of the vagal trunks, etc.). In some examples, the wires 108 may be referenced as cuff electrodes or may otherwise include the cuff electrodes (e.g., at an end of the wires 108 not connected or plugged into the device 104). Additionally or alternatively, while shown as physical wires that provide the connection between the device 104 and the one or more vagal trunks, the cuff electrodes may provide the electrical blocking and/or stimulation signals to the one or more vagal trunks wirelessly (e.g., with or without the device 104).

Additionally, while not shown, the system 100 may include one or more processors (e.g., one or more DSPs, general purpose microprocessors, graphics processing units, ASICs, FPGAs, or other equivalent integrated or discrete logic circuitry) that are programmed to carry out one or more aspects of the present disclosure. In some examples, the one or more processors may include a memory or may be otherwise configured to perform the aspects of the present disclosure. For example, the one or more processors may provide instructions to the device 104, the cuff electrodes, or other components of the system 100 not explicitly shown or described with reference to FIG. 1 for providing the stimulation/blocking therapy to promote glycemic control in a patient as described herein. In some examples, the one or more processors may be part of the device 104 or part of a control unit for the system 100 (e.g., where the control unit is in communication with the device 104 and/or other components of the system 100).

In some examples, the system 100 may also optionally include a glucose sensor 120 that communicates (e.g., wirelessly) with other components of the system 100 (e.g., the device 104, the one or more processors, etc.) to achieve better glycemic control in the patient. For example, the glucose sensor 120 may continuously monitor glucose levels of the patient, such that if the glucose sensor 120 determines glucose levels are outside a normal or desired range for the patient (e.g., glucose levels are too high or too low in the patient), the glucose sensor 120 may communicate that glucose levels are outside the normal or desired range to the device 104 (e.g., via the one or more processors) to signal for the device 104 to apply the stimulation/blocking therapy described herein to adjust glucose levels in the patient (e.g., mute the glycemic response to lower glucose levels in the patient, block insulin production in the patient as a possible technique to raise glucose levels in the patient, etc.).

The system 100 or similar systems may be used, for example, to carry out one or more aspects of any of the methods 400 and/or 500 described herein. The system 100 or similar systems may also be used for other purposes. It will be appreciated that the human body has many vagal nerves and the stimulation and/or blocking therapies described herein may be applied to one or more vagal nerves, which may reside at any location of a patient (e.g., lumbar, thoracic, etc.). Further, a sequence of stimulations and/or blocking therapies may be applied to different nerves. For example, a low frequency stimulation may be applied to a first nerve and a high frequency blockade may be applied to a second nerve.

FIG. 2 depicts a system 200 that uses growth curves for optimizing a type 2 diabetes treatment according to at least one embodiment of the present disclosure. In some examples, the system 200 may implement aspects of or may be implemented by aspects of the system 100 as described with reference to FIG. 1. For example, the system 200 may include a nerve fiber 204, which may represent a fiber on a branch of the vagus nerve as described with reference to FIG. 1. In some examples, the nerve fiber 204 may represent a nerve fiber on a branch of a celiac vagal trunk and/or a nerve fiber on a hepatic vagal trunk. Additionally, the system 200 may include a stimulation electrode 208 (e.g., a first electrode device) and a record electrode 212, which may represent examples of the cuff electrodes or electrode devices as described with reference to FIG. 1 (e.g., disposed at the end of a wire 108). For example, the stimulation electrode 208 may include a first body and a first plurality of electrodes disposed on the first body, where the first plurality of electrodes is configured to apply a current to an anatomical element (e.g., the nerve fiber 204). Additionally, the record electrode 212 may include a second body and a second plurality of electrodes disposed on the second body, where the second plurality of electrodes are configured to record measurements corresponding to the current when the current is applied to the anatomical element.

As described herein, the system 200 may be used to perform a calibration and/or optimization procedure for determining optimal parameters for applying a current to the nerve fiber 204 to achieve a desired glycemic response in a patient. For example, the desired glycemic response as used herein may correspond to a glycemic response the patient is satisfied and comfortable with and/or a glycemic response that includes a peak post prandial glycemic level that stays within an acceptable range (e.g., glycemic levels above this range may cause harm to the patient over time and glycemic levels below this range may cause hypoglycemia in the patient). Additionally or alternatively, the system 200 may be used to perform the calibration and/or optimization procedure for the stimulation/block therapy described herein for determining optimal parameters for applying the current to the nerve fiber 204 based on a downstream action potential that is recorded when an upstream stimulation is applied.

The stimulation electrode 208 and the record electrode 212 may be configured to be placed on the nerve fiber 204 (e.g., a nerve fiber on a celiac vagal trunk and/or a hepatic vagal trunk). The stimulation electrode 208 may be configured to apply the current to the nerve fiber 204, and the record electrode 212 may be configured to record measurements corresponding to the current when the current is applied to the nerve fiber 204. In some examples, the stimulation electrode 208 may apply the current to the nerve fiber 204 using a set of parameters (e.g., a given amplitude, frequency, etc.) that correspond to an expected physiological response. The record electrode 212 may record measurements on the nerve fiber 204 as the current is being applied via the stimulation electrode 208. Subsequently, if the record electrode 212 records measurements that are inconsistent with the expected physiological response, one or more parameters of the set of parameters used to apply the current to the nerve fiber 204 may be adjusted to achieve the expected physiological response and/or the desired glycemic response. For example, an amplitude, a frequency, and/or a charge density of the current may be adjusted.

In some examples, the measurements recorded by the record electrode 212 (e.g., response measurements) may include stimulus eCAP measurements, EMG measurements (e.g., measures of a muscle response or electrical activity in response to stimulating a nerve of the muscle or a nerve near the muscle), glucose level measurements (e.g., how glucose levels in the patient change when the stimulation electrode 208 applies the current to the nerve fiber 204 as measured, for example, by the glucose sensor 120 as described with reference to FIG. 2 or a continuous glucose monitor), or a different measurement indicative of effects of the current being applied to the nerve fiber 204. Additionally, the record electrode 212 may record a plurality of measurements over a period of time that at least coincides with a duration of the current being applied to the nerve fiber 204 via the stimulation electrode 208. Accordingly, one or more growth curves may be generated based on the plurality of measurements recorded by the record electrode 212.

Growth curves are graphical representations that show the course of a phenomenon over time, such as an empirical model of the evolution of a quantity over time. As described herein, the growth curves generated may represent how the plurality of measurements fluctuate over the period of time for which they are recorded by the record electrode 212 and while the current is applied to the nerve fiber 204 by the stimulation electrode. For example, the growth curves may illustrate increasing a stimulus value and plotting response measurements, such as an eCAP amplitude or an EMG amplitude or glucose levels that change as the stimulus value is increased. That is, eCAP and/or EMG measurements may change with increasing stimulus levels (e.g., increasing amplitudes of the current being applied to the anatomical element, such as from 2 milliamps (mA) to 5 mA to 10 mA or other steps of increased stimulus levels), where the growth curves plots how the eCAP and/or EMG measurements change for each of the increased stimulus levels. Similarly, glucose levels in the patient (e.g., as recorded by a glucose sensor or continuous glucose monitor of the patient) may change based on increasing stimulus levels of the stimulation/block therapy described herein, such that a slope corresponding to a glucose response curve (e.g., how the glucose levels change with increasing stimulus levels) could be dependent on stimulus level. Accordingly, the slope of the glucose response curve may be monitored, and stimulus levels of the therapy can be adjusted based on a required or desired slope.

The generated growth curves may then be used in conjunction with values of the set of parameters used to apply the current to the nerve fiber 204 to determine an optimal set of parameters for applying the current. For example, the record electrode 212 (e.g., or another component) may record values for one or more of the set of parameters used to apply the current to the nerve fiber 204, where the values are recorded at each instance that a measurement of the plurality of measurements is recorded. That is, at each instance that the record electrode 212 records a measurement of the plurality of measurements, the record electrode 212 may also record corresponding values for the set of parameters used to apply the current to the nerve fiber 204 at those same instances. Subsequently, a maximum measurement of the plurality of measurements may correspond to optimal values for the set of parameters that are recorded at a same time instance that the maximum measurement is recorded. In some examples, the optimal values for the set of parameters may be optimal for applying the current to the anatomical element to achieve the desired glycemic response in the patient. Accordingly, the set of parameters for applying the current to the nerve fiber 204 may be adjusted based on the optimal values.

In some examples, the system 200 may be used to determine if one or more operational issues are present for the stimulation/block therapy as described herein. For example, if the record electrode 212 records measurements that are different than expected results when the stimulation electrode 208 applies the current to the nerve fiber 204, it may be determined that one or more of the operational issues are present. For example, the one or more operational issues may include a fibrous growth on the anatomical element affecting application of the current via the stimulation electrode 208, the stimulation electrode 208 and/or the record electrode 212 not being properly placed on the nerve fiber 204, the nerve fiber 204 being too large for proper placement of the stimulation electrode 208 and/or the record electrode 212, or a combination thereof. Subsequently, a medical professional (e.g., nurse, physician, clinician, etc.) may perform a troubleshooting to determine if the one or more operational issues are present based on the record electrode 212 recording measurements that are different than expected results when the stimulation electrode 208 applies the current to the nerve fiber 204.

FIG. 3 depicts a block diagram of a system 300 according to at least one embodiment of the present disclosure is shown. In some examples, the system 300 may implement aspects of or may be implemented by aspects of FIGS. 1-2 as described herein. For example, the system 300 may be used with an implantable pulse generator 316 and/or an electrode device 318, and/or carry out one or more other aspects of one or more of the methods disclosed herein. The implantable pulse generator 316 may represent an example of the device 104 or a component of the device 104 as described with reference to FIG. 1. Additionally, the electrode devices 318 may represent the wires 108 and corresponding electrodes/cuff electrodes as described with reference to FIG. 1 and/or the stimulation electrode 208 and the record electrode 212 as described with reference to FIG. 2. The system 300 comprises a computing device 302, a system 312, a database 330, and/or a cloud or other network 334. Systems according to other embodiments of the present disclosure may comprise more or fewer components than the system 300. For example, the system 300 may not include one or more components of the computing device 302, the database 330, and/or the cloud 334.

The system 312 may comprise the implantable pulse generator 316 and one or more electrode devices 318. As previously described, the implantable pulse generator 316 may be configured to generate a current, and the electrode devices 318 may comprise a first plurality of electrodes (e.g., of a first electrode device) configured to apply the current to an anatomical element and a second plurality of electrodes (e.g., of a second electrode device) configured to record measurements corresponding to the current when applied to the anatomical element. The system 312 may communicate with the computing device 302 to receive instructions such as instructions 324 for applying a current to the anatomical element via the first plurality of electrodes and/or record response measurements via the second plurality of electrodes when the current is applied. The system 312 may also provide data (such as data received from an electrode device 318 capable of recording data), which may be used to optimize the electrodes of the electrode device 318 and/or to optimize parameters of the current generated by the implantable pulse generator 316.

The computing device 302 comprises a processor 304, a memory 306, a communication interface 308, and a user interface 310. Computing devices according to other embodiments of the present disclosure may comprise more or fewer components than the computing device 302.

The processor 304 of the computing device 302 may be any processor described herein or any similar processor. The processor 304 may be configured to execute instructions 324 stored in the memory 306, which instructions may cause the processor 304 to carry out one or more computing steps utilizing or based on data received from the system 312, the database 330, and/or the cloud 334.

The memory 306 may be or comprise RAM, DRAM, SDRAM, other solid-state memory, any memory described herein, or any other tangible, non-transitory memory for storing computer-readable data and/or instructions. The memory 306 may store information or data useful for completing, for example, any steps of the methods 400 and/or 500 described herein, or of any other methods. The memory 306 may store, for example, instructions and/or machine learning models that support one or more functions of the system 312. For instance, the memory 306 may store content (e.g., instructions and/or machine learning models) that, when executed by the processor 304, enable current optimization 322.

The current optimization 322 enables the processor 304 to determine optimal parameters for applying the current to the anatomical element of the patient. For example, as described with reference to FIGS. 1-2, the current may be applied to the anatomical element via a first electrode device (e.g., stimulation electrode) of the electrode devices 318, and a second electrode device (e.g., record electrode) of the electrode devices 318 may record measurements while the current is being applied. Using the measurements, the processor 304 may determine the optimal parameters for applying the current via the current optimization 322. For example, the optimal parameters for applying the current may be determined to be optimal based on achieving a desired glycemic response in the patient and/or based on a downstream action potential that is recorded when an upstream stimulation is applied.

Content stored in the memory 306, if provided as in instruction, may, in some embodiments, be organized into one or more applications, modules, packages, layers, or engines. Alternatively or additionally, the memory 306 may store other types of content or data (e.g., machine learning models, artificial neural networks, deep neural networks, etc.) that can be processed by the processor 304 to carry out the various method and features described herein. Thus, although various contents of memory 306 may be described as instructions, it should be appreciated that functionality described herein can be achieved through use of instructions, algorithms, and/or machine learning models. The data, algorithms, and/or instructions may cause the processor 304 to manipulate data stored in the memory 306 and/or received from or via the system 312, the database 330, and/or the cloud 334.

The computing device 302 may also comprise a communication interface 308. The communication interface 308 may be used for receiving data (for example, data from an electrode device 318 capable of recording data) or other information from an external source (such as the system 312, the database 330, the cloud 334, and/or any other system or component not part of the system 300), and/or for transmitting instructions, images, or other information to an external system or device (e.g., another computing device 302, the system 312, the database 330, the cloud 334, and/or any other system or component not part of the system 300). The communication interface 308 may comprise one or more wired interfaces (e.g., a USB port, an Ethernet port, a Firewire port) and/or one or more wireless transceivers or interfaces (configured, for example, to transmit and/or receive information via one or more wireless communication protocols such as 802.11a/b/g/n, Bluetooth, NFC, ZigBee, and so forth). In some embodiments, the communication interface 308 may be useful for enabling the device 302 to communicate with one or more other processors 304 or computing devices 302, whether to reduce the time needed to accomplish a computing-intensive task or for any other reason.

The computing device 302 may also comprise one or more user interfaces 310. The user interface 310 may be or comprise a keyboard, mouse, trackball, monitor, television, screen, touchscreen, and/or any other device for receiving information from a user and/or for providing information to a user. The user interface 310 may be used, for example, to receive a user selection or other user input regarding any step of any method described herein. Notwithstanding the foregoing, any required input for any step of any method described herein may be generated automatically by the system 300 (e.g., by the processor 304 or another component of the system 300) or received by the system 300 from a source external to the system 300. In some embodiments, the user interface 310 may be useful to allow a surgeon or other user to modify instructions to be executed by the processor 304 according to one or more embodiments of the present disclosure, and/or to modify or adjust a setting of other information displayed on the user interface 310 or corresponding thereto.

Although the user interface 310 is shown as part of the computing device 302, in some embodiments, the computing device 302 may utilize a user interface 310 that is housed separately from one or more remaining components of the computing device 302. In some embodiments, the user interface 310 may be located proximate one or more other components of the computing device 302, while in other embodiments, the user interface 310 may be located remotely from one or more other components of the computer device 302.

Though not shown, the system 300 may include a controller, though in some embodiments the system 300 may not include the controller. The controller may be an electronic, a mechanical, or an electro-mechanical controller. The controller may comprise or may be any processor described herein. The controller may comprise a memory storing instructions for executing any of the functions or methods described herein as being carried out by the controller. In some embodiments, the controller may be configured to simply convert signals received from the computing device 302 (e.g., via a communication interface 308) into commands for operating the system 312 (and more specifically, for actuating the implantable pulse generator 316 and/or the electrode device 318). In other embodiments, the controller may be configured to process and/or convert signals received from the system 312. Further, the controller may receive signals from one or more sources (e.g., the system 312) and may output signals to one or more sources.

The database 330 may store information such as patient data, results of a stimulation and/or blocking procedure, stimulation and/or blocking parameters, current parameters, electrode parameters, etc. The database 330 may be configured to provide any such information to the computing device 302 or to any other device of the system 300 or external to the system 300, whether directly or via the cloud 334. In some embodiments, the database 330 may be or comprise part of a hospital image storage system, such as a picture archiving and communication system (PACS), a health information system (HIS), and/or another system for collecting, storing, managing, and/or transmitting electronic medical records.

The cloud 334 may be or represent the Internet or any other wide area network. The computing device 302 may be connected to the cloud 334 via the communication interface 308, using a wired connection, a wireless connection, or both. In some embodiments, the computing device 302 may communicate with the database 330 and/or an external device (e.g., a computing device) via the cloud 334.

The system 300 or similar systems may be used, for example, to carry out one or more aspects of any of the methods 400 and/or 500 as described herein. The system 300 or similar systems may also be used for other purposes.

FIG. 4 depicts a method 400 that may be used, for example, for optimization of a stimulation/block therapy for treatment of type 2 diabetes.

The method 400 (and/or one or more steps thereof) may be carried out or otherwise performed, for example, by at least one processor. The at least one processor may be the same as or similar to the processor(s) of the device 104 described above. The at least one processor may be part of the device 104 (such as an implantable pulse generator) or part of a control unit in communication with the device 104. A processor other than any processor described herein may also be used to execute the method 400. The at least one processor may perform the method 400 by executing elements stored in a memory (such as a memory in the device 104 as described above or a control unit). The elements stored in the memory and executed by the processor may cause the processor to execute one or more steps of a function as shown in method 400. One or more portions of a method 400 may be performed by the processor executing any of the contents of memory, such as providing a stimulation/block therapy and/or any associated operations as described herein.

The method 400 comprises transmitting instructions to a device (e.g., the device 104 as described with reference to FIG. 1, such as an implantable pulse generator) to apply a current to an anatomical element of a patient via a first electrode device, where the current is applied using a set of parameters that correspond to an expected physiological response (step 404). For example, the first electrode device may be an example of a stimulation electrode 208 as described with reference to FIG. 2. In some examples, the current being applied to the anatomical element may be intended to reduce a glycemic response in the patient (e.g., as a form of treatment for type 2 diabetes in the patient). Additionally, the anatomical element may include a celiac vagal trunk, a hepatic vagal trunk, or both of the patient.

The method 400 also comprises receiving a response measurement recorded via the second electrode device based at least in part on applying the current via the first electrode device (step 408). For example, the second electrode device may be an example of a record electrode 212 as described with reference to FIG. 2. In some examples, the response measurement may include an eCAP measurement, an EMG measurement, a glucose level measurement, and/or a different measurement that is indicative of the current being applied to the anatomical element via the first electrode device (e.g., a downstream action potential that is recorded when an upstream stimulation is applied).

The method 400 also comprises adjusting one or more parameters of the set of parameters for the device to apply the current based at least in part on the response measurement being different than the expected physiological response (step 412). For example, an amplitude, frequency, charge density, or a combination thereof may be adjusted for the current. In some examples, the response measurement being different than the expected physiological response may indicate an operational issue. For example, the operational issue may include a fibrous growth on the anatomical element that affects applying the current via the first electrode, the first electrode and/or the second electrode not being properly placed on the anatomical element, the anatomical element being too large for proper placement of the first electrode and/or the second electrode, or a combination thereof.

In some examples, the at least one processor may perform the steps of the method 400 based on performing a calibration procedure. For example, the calibration procedure may be performed to determine optimal parameters for applying the current to the anatomical element to achieve a desired glycemic response in the patient and/or to determine optimal parameters for applying the current to the anatomical element based on a downstream action potential that is recorded when an upstream stimulation is applied. Additionally or alternatively, the at least one processor may perform the steps of the method 400 based on a detected issue with the stimulation/block therapy (e.g., the stimulation/block therapy is not performing as expected or is not producing expected results for the patient). Accordingly, the method 400 may be used to determine why the stimulation/block therapy is performing incorrectly, to determine optimal parameters for the stimulation/block therapy, to calibrate the stimulation/block therapy, or a combination thereof.

The present disclosure encompasses embodiments of the method 400 that comprise more or fewer steps than those described above, and/or one or more steps that are different than the steps described above.

FIG. 5 depicts a method 500 that may be used, for example, to leverage growth curves for optimization of a stimulation/block therapy for treatment of type 2 diabetes.

The method 500 (and/or one or more steps thereof) may be carried out or otherwise performed, for example, by at least one processor. The at least one processor may be the same as or similar to the processor(s) of the device 104 described above. The at least one processor may be part of the device 104 (such as an implantable pulse generator) or part of a control unit in communication with the device 104. A processor other than any processor described herein may also be used to execute the method 500. The at least one processor may perform the method 500 by executing elements stored in a memory (such as a memory in the device 104 as described above or a control unit). The elements stored in the memory and executed by the processor may cause the processor to execute one or more steps of a function as shown in method 500. One or more portions of a method 500 may be performed by the processor executing any of the contents of memory, such as providing a stimulation/block therapy and/or any associated operations as described herein.

The method 500 comprises transmitting instructions to a device (e.g., the device 104 as described with reference to FIG. 1, such as an implantable pulse generator) to apply a current to an anatomical element of a patient via a first electrode device, where the current is applied using a set of parameters that correspond to an expected physiological response (step 504). The method 500 also comprises receiving a response measurement recorded via the second electrode device based at least in part on applying the current via the first electrode device (step 508). Steps 504 and 508 may implement aspects of the steps 404 and 408 as described with reference to FIG. 4. For example, the first electrode device may be an example of a stimulation electrode 208 as described with reference to FIG. 2, and the second electrode device may be an example of a record electrode 212 as described with reference to FIG. 2. Additionally, the response measurement recorded and received via the second electrode device may include an eCAP measurement, an EMG measurement, a glucose level measurement, a different measurement that is indicative of the current being applied to the anatomical element via the first electrode device (e.g., a downstream action potential that is recorded when an upstream stimulation is applied), or a combination thereof.

The method 500 also comprises receiving a plurality of response measurements recorded via the second electrode device over a period of time, the period of time coinciding at least with a duration of the current being applied to the anatomical element (step 512). The method 500 also comprises generating one or more growth curves based at least in part on the plurality of response measurements (step 516). In some examples, one or more parameters used for applying the current to the anatomical element may be adjusted based at least in part on the one or more growth curves.

The method 500 also comprises receiving values for one or more of the set of parameters used to apply the current to the anatomical element (step 520). For example, the values may be recorded via the second electrode device at each instance that a response measurement of the plurality of response measurements is recorded. In some examples, a maximum response measurement of the plurality of response measurements may correspond to optimal values for the set of parameters recorded at a same time instance that the maximum response measurement is recorded. The optimal values for the set of parameters may be optimal for applying the current to the anatomical element to achieve a desired glycemic response in the patient. Additionally or alternatively, the optimal values for the set of parameters may be determined based on a downstream action potential that is recorded when an upstream stimulation is applied (e.g., the response measurement as described and referenced herein), such that a specific downstream action potential measurement may correspond to the optimal values.

The method 500 also comprises adjusting one or more parameters of the set of parameters for the device to apply the current based at least in part on the response measurement being different than the expected physiological response (step 524). Additionally, the one or more parameters may be adjusted based at least in part on the optimal values determined in part by the values received at step 520.

The present disclosure encompasses embodiments of the method 500 that comprise more or fewer steps than those described above, and/or one or more steps that are different than the steps described above.

As noted above, the present disclosure encompasses methods with fewer than all of the steps identified in FIGS. 4 and 5 (and the corresponding description of the methods 400 and 500), as well as methods that include additional steps beyond those identified in FIGS. 4 and 5 (and the corresponding description of the methods 400 and 500). The present disclosure also encompasses methods that comprise one or more steps from one method described herein, and one or more steps from another method described herein. Any correlation described herein may be or comprise a registration or any other correlation.

The foregoing is not intended to limit the disclosure to the form or forms disclosed herein. In the foregoing Detailed Description, for example, various features of the disclosure are grouped together in one or more aspects, embodiments, and/or configurations for the purpose of streamlining the disclosure. The features of the aspects, embodiments, and/or configurations of the disclosure may be combined in alternate aspects, embodiments, and/or configurations other than those discussed above. This method of disclosure is not to be interpreted as reflecting an intention that the claims require more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive aspects lie in less than all features of a single foregoing disclosed aspect, embodiment, and/or configuration. Thus, the following claims are hereby incorporated into this Detailed Description, with each claim standing on its own as a separate preferred embodiment of the disclosure.

Moreover, though the foregoing has included description of one or more aspects, embodiments, and/or configurations and certain variations and modifications, other variations, combinations, and modifications are within the scope of the disclosure, e.g., as may be within the skill and knowledge of those in the art, after understanding the present disclosure. It is intended to obtain rights which include alternative aspects, embodiments, and/or configurations to the extent permitted, including alternate, interchangeable and/or equivalent structures, functions, ranges or steps to those claimed, whether or not such alternate, interchangeable and/or equivalent structures, functions, ranges or steps are disclosed herein, and without intending to publicly dedicate any patentable subject matter.

Claims

1. A system for stimulating an anatomical element of a patient, comprising:

an implantable pulse generator configured to generate a current;

a first electrode device electrically coupled to the implantable pulse generator, the first electrode device comprising a first plurality of electrodes configured for placement on or around the anatomical element of the patient;

a second electrode device electrically coupled to the implantable pulse generator, the second electrode device comprising a second plurality of electrodes configured for placement on or around the anatomical element of the patient;

a processor; and

a memory storing data for processing by the processor, the data, when processed, causes the processor to: transmit instructions to the implantable pulse generator to apply the current to the anatomical element of the patient via the first electrode device, wherein the current is applied using a set of parameters that correspond to an expected physiological response; receive a response measurement recorded via the second electrode device based at least in part on applying the current via the first electrode device; and adjust one or more parameters of the set of parameters for the implantable pulse generator to apply the current based at least in part on the response measurement being different than the expected physiological response.

2. The system of claim 1, wherein the data stored in the memory that, when processed causes the processor to adjust the one or more parameters causes the system to:

adjust an amplitude, frequency, charge density, or a combination thereof for the current.

3. The system of claim 1, wherein the response measurement comprises an evoked compound action potential (eCAP) measurement, an electromyography (EMG) measurement, a glucose level measurement, or a combination thereof.

4. The system of claim 3, wherein the memory stores further data for processing by the processor that, when processed, causes the processor to:

receive a plurality of response measurements recorded via the second electrode device over a period of time, the period of time coinciding at least with a duration of the current being applied to the anatomical element; and

generate one or more growth curves based at least in part on the plurality of response measurements, wherein the one or more parameters are adjusted based at least in part on the one or more growth curves.

5. The system of claim 4, wherein the memory stores further data for processing by the processor that, when processed, causes the processor to:

receive values for one or more of the set of parameters used to apply the current to the anatomical element, the values recorded via the second electrode device at each instance that a response measurement of the plurality of response measurements is recorded.

6. The system of claim 5, wherein a maximum response measurement of the plurality of response measurements corresponds to optimal values for the set of parameters recorded at a same time instance that the maximum response measurement is recorded, the optimal values for the set of parameters being optimal for applying the current to the anatomical element to achieve a desired glycemic response in the patient.

7. The system of claim 6, wherein the one or more parameters are adjusted based at least in part on the optimal values.

8. The system of claim 1, wherein the response measurement being different than the expected physiological response indicates an operational issue.

9. The system of claim 8, wherein the operational issue comprises a fibrous growth on the anatomical element that affects applying the current via the first electrode, the first electrode and/or the second electrode not being properly placed on the anatomical element, the anatomical element being too large for proper placement of the first electrode, or a combination thereof.

10. The system of claim 1, wherein the current being applied to the anatomical element reduces a glycemic response in the patient.

11. The system of claim 1, wherein the anatomical element comprises a celiac vagal trunk, a hepatic vagal trunk, or both of the patient.

12. A system for stimulating an anatomical element of a patient, comprising:

an implantable pulse generator configured to generate a current;

a first electrode device comprising: a first body; and a first plurality of electrodes disposed on the first body and configured to apply the current to the anatomical element;

a second electrode device comprising: a second body; and a second plurality of electrodes disposed on the second body and configured to record measurements corresponding to the current when the current is applied to the anatomical element;

a processor; and

a memory storing data for processing by the processor, the data, when processed, causes the processor to: transmit instructions to the implantable pulse generator to apply the current to the anatomical element of the patient via the first electrode device, wherein the current is applied using a set of parameters that correspond to an expected physiological response; receive a response measurement recorded via the second electrode device based at least in part on applying the current via the first electrode device; and adjust one or more parameters of the set of parameters for the implantable pulse generator to apply the current based at least in part on the response measurement being different than the expected physiological response.

13. The system of claim 12, wherein the data stored in the memory that, when processed causes the processor to adjust the one or more parameters causes the system to:

adjust an amplitude, frequency, charge density, or a combination thereof for the current.

14. The system of claim 12, wherein the response measurement comprises an evoked compound action potential (eCAP) measurement, an electromyography (EMG) measurement, a glucose level measurement, or a combination thereof.

15. The system of claim 14, wherein the memory stores further data for processing by the processor that, when processed, causes the processor to:

receive a plurality of response measurements recorded via the second electrode device over a period of time, the period of time coinciding at least with a duration of the current being applied to the anatomical element; and

generate one or more growth curves based at least in part on the plurality of response measurements, wherein the one or more parameters are adjusted based at least in part on the one or more growth curves.

16. The system of claim 15, wherein the memory stores further data for processing by the processor that, when processed, causes the processor to:

receive values for one or more of the set of parameters used to apply the current to the anatomical element, the values recorded via the second electrode device at each instance that a response measurement of the plurality of response measurements is recorded.

17. The system of claim 16, wherein a maximum response measurement of the plurality of response measurements corresponds to optimal values for the set of parameters recorded at a same time instance that the maximum response measurement is recorded, the optimal values for the set of parameters being optimal for applying the current to the anatomical element to achieve a desired glycemic response in the patient.

18. The system of claim 17, wherein the one or more parameters are adjusted based at least in part on the optimal values.

19. A system for stimulating an anatomical element of a patient, comprising:

an implantable pulse generator configured to generate a current;

a first electrode device electrically coupled to the implantable pulse generator, the first electrode device comprising a first plurality of electrodes for placement on or around the anatomical element of the patient, wherein the first plurality of electrodes is configured to apply the current to the anatomical element; and

a second electrode device electrically coupled to the implantable pulse generator, the second electrode device comprising a second plurality of electrodes for placement on or around the anatomical element of the patient, wherein the second plurality of electrodes is configured to record measurements corresponding to the current when the current is applied to the anatomical element.

20. The system of claim 19, wherein the current being applied to the anatomical element via the first electrode device reduces a glycemic response in the patient.