CONTROL OF VAGAL STIMULATION

• US 20170203103A1
• Filed: 01/20/2017
• Published: 07/20/2017
• Est. Priority Date: 01/20/2016
• Status: Active Grant

• Current Assignee: Setpoint Medical Corporation
• Original Assignee: Jacob A. Levine, Jesse M. Simon, Mike A Faltys
• Inventors: SIMON, Jesse M., LEVINE, Jacob A., FALTYS, Michael A.
• Granted Patent: US 10,695,569 B2
• Time in Patent Office: Days
• CPC Class Codes: A61B 5/02405 Determining heart rate variability
• CPC Class Codes: A61B 5/352 Detecting R peaks, e.g. for synchronising diagnostic apparatus; Estimating R-R interval
• CPC Class Codes: A61B 5/4035 Evaluating the autonomic nervous system
• CPC Class Codes: A61B 5/4836 Diagnosis combined with treatment in closed-loop systems or methods A61B5/0036 takes precedence
• CPC Class Codes: A61B 5/7257 using Fourier transforms
• CPC Class Codes: A61N 1/0556 Cuff electrodes
• CPC Class Codes: A61N 1/36053 adapted for vagal stimulation A61N1/36114 takes precedence
• CPC Class Codes: A61N 1/3606 adapted for a particular treatment
• CPC Class Codes: A61N 1/36135 using physiological parameters
• CPC Class Codes: A61N 1/37205 Microstimulators, e.g. implantable through a cannula
• CPC Class Codes: A61N 1/37247 User interfaces, e.g. input or presentation means
• CPC Class Codes: A61N 1/3756 Casings with electrodes thereon, e.g. leadless stimulators
• CPC Class Codes: A61N 1/3787 from an external energy source

Abstract

Methods and apparatuses for stimulation of the vagus nerve to treat inflammation including adjusting the stimulation based on one or more metric sensitive to patient response. The one or more metrics may include heart rate variability, level of T regulatory cells, particularly memory T regulatory cells, temperature, etc. Stimulation may be provided through an implantable microstimulator.

Claims

1. A method for treating inflammation in a subject, the method comprising:

measuring a first heart rate variability from the subject using an electrode of an implantable microstimulator, wherein the electrode is in electrical contact with the subject'"'"'s vagus nerve;

applying a first electrical stimulation to the subject'"'"'s vagus nerve from the electrode;

measuring a second heart rate variability from the subject after the first electrical stimulation; and

applying a second electrical stimulation to the subject'"'"'s vagus nerve based on the first heart rate variability and the second heart rate variability.

2. The method of claim 1, further comprising measuring a second metric from the patient, and further wherein applying the second electrical stimulation is based on the first heart rate variability, the second heart rate variability and the second metric.

3. The method of claim 2, wherein the second metric comprises one or more of:

temperature, activity, cytokine level, memory T cell level.

4. The method of claim 1, wherein applying the second electrical stimulation to the subject comprises increasing or decreasing the stimulation based on the first heart rate variability and the second heart rate variability.

5. The method of claim 4, wherein increasing or decreasing the stimulation comprises increasing or decreasing one or more of:

the frequency of stimulation, the duration of stimulation, the burst duration, the amplitude of electrical stimulation, and the peak-to-peak voltage of the stimulation.

6. The method of claim 1, wherein applying the second electrical stimulation to the subject'"'"'s vagus nerve based on the first heart rate variability and the second heart rate variability comprises determining a ratio of high frequency to low frequency components of heart rate variability.

7. The method of claim 1, wherein the second electrical stimulation is applied after an off-period of between 30 minutes and 24 hours.

8. The method of claim 1, wherein the electrode is in contact with the subject'"'"'s vagus nerve in the patient'"'"'s cervical region.

9. A leadless, implantable microstimulator apparatus for treating chronic inflammation in a patient, the apparatus comprising:

a housing having a channel through which a nerve may pass;

at least two electrically conductive contacts;

a motion sensor within the housing, the motion sensor configured to measure physical activity of the patient;

a power source within the housing;

an electronic assembly within the housing, wherein the electronic assembly comprises a controller configured to apply stimulation to the vagus nerve from the electrically conductive contacts and to measure heart rate variability from the electrically conductive contacts;

further wherein the controller is configured to adjust the applied stimulation based on the measurement of heart rate variability; and

a protection an orientation (POD) cuff configured to hold the housing over the nerve so that the nerve is in electrical communication with the electrically conductive contacts.

10. The apparatus of claim 9, wherein the motion sensor comprises an accelerometer.

11. The apparatus of claim 9, wherein the controller is configured to adjust the stimulation based on the measurement of heart rate variability and the measured physical activity.

12. The apparatus of claim 9, wherein the controller is configured to measure heart rate variability when the patient is at rest based on the motion sensor.

13. The apparatus of claim 9, wherein, based on the measurement of heart rate variability, the controller adjusts one or more of:

a stimulation amplitude, a stimulation duration, and a stimulation frequency of application.

14. The apparatus of claim 9, wherein the controller is configured increase one or more stimulation parameters when a decrease in physical activity is measured by the accelerometer.

15. A method for treating inflammation in a subject, the method comprising:

measuring a first level of memory T regulatory cells in the subject;

applying a first stimulation to the subject'"'"'s vagus nerve;

measuring a second level of memory T regulatory cells in the subject after the first stimulation; and

applying a second stimulation to the subject'"'"'s vagus nerve based on the first and second levels of memory T regulatory cells measured.

16. The method of claim 15, further comprising comparing the first level of memory T regulatory cells to the second level of memory T regulatory cells.

17. The method of claim 15, wherein the second stimulation is greater than than the first stimulation by at least a predetermined amount in one or more of:

the frequency of stimulation, the duration of stimulation, the burst duration, the amplitude of electrical stimulation, and the peak-to-peak voltage of the stimulation.

18. The method of claim 15, wherein the second stimulation is less than than the first stimulation by at least a predetermined amount in one or more of:

the frequency of stimulation, the duration of stimulation, the burst duration, the amplitude of electrical stimulation, and the peak-to-peak voltage of the stimulation.

19. The method of claim 17, wherein the predetermined amount is 10 percent.

20. The method of claim 18, wherein the predetermined amount is 10 percent.

21. The method of claim 15, wherein applying the second stimulation to the subject'"'"'s vagus nerve comprises applying electrical stimulation from an implanted microstimulator.

22. The method of claim 15, wherein applying the first stimulation to the subject'"'"'s vagus nerve comprises applying a non-invasive stimulation to the subject'"'"'s vagus nerve.

23. The method of claim 15, wherein measuring a first level of memory T regulatory cells comprises determining a level of CD4+CD25+CD127LowCD45RO+ cells in a sample of blood from the subject.

24. The method of claim 15, wherein measuring a first level of memory T regulatory cells comprises determining a level of expression of FOXP3 in a sample of blood from the subject.

25. The method of claim 15, wherein applying the first stimulation to the subject'"'"'s vagus nerve comprises applying a minimally-invasive stimulation to the subject'"'"'s vagus nerve.

26. The method of claim 25, wherein the minimally invasive stimulation comprises stimulation from a needle electrode.

27. A method of setting a dosage level for electrically stimulating a subject'"'"'s vagus nerve for treating inflammation, the method comprising:

measuring a baseline level of memory T regulatory cells in a sample of the subject'"'"'s blood;

applying a first stimulation to the subject'"'"'s vagus nerve;

measuring a post-stimulation level of memory T regulatory cells in a sample of the patient'"'"'s blood taken after applying the first stimulation to the subject'"'"'s vagus nerve;

comparing the baseline level of memory T regulatory cells to the post-stimulation level;

adjusting at least one parameter of the first stimulation based on the baseline level of memory T regulatory cells and the post-stimulation level of memory T regulatory cells; and

applying a second stimulation to the subject'"'"'s vagus nerve using the adjusted at least one parameter.