Control of vagal stimulation

• US 10,695,569 B2
• Filed: 01/20/2017
• Issued: 06/30/2020
• Est. Priority Date: 01/20/2016
• Status: Active Grant

• Current Assignee: Setpoint Medical Corporation
• Original Assignee: Setpoint Medical Corporation
• Inventors: Levine, Jacob A., Faltys, Michael A., Simon, Jesse M.
• Primary Examiner(s): Mahmood, Nadia A
• Application Number:
  US15/411,933
• Publication Number:
  US 20170203103A1
• Time in Patent Office: 1,257 Days
• Field of Search: 607 2
• 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 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.

2. The method of claim 1, further comprising comparing the first level of memory T regulatory cells to the second level of memory T regulatory cells.

3. The method of claim 1, wherein the second stimulation is greater 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.

4. The method of claim 1, wherein the second stimulation is less 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.

5. The method of claim 3, wherein the predetermined amount is 10 percent.

6. The method of claim 4, wherein the predetermined amount is 10 percent.

7. The method of claim 1, wherein applying the second stimulation to the subject'"'"'s vagus nerve comprises applying electrical stimulation from an implanted microstimulator.

8. The method of claim 1, wherein applying the first stimulation to the subject'"'"'s vagus nerve comprises applying a non-invasive stimulation to the subject'"'"'s vagus nerve.

9. The method of claim 1, 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.

10. The method of claim 1, 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.

11. The method of claim 1, wherein applying the first stimulation to the subject'"'"'s vagus nerve comprises applying a minimally-invasive stimulation to the subject'"'"'s vagus nerve.

12. The method of claim 11, wherein the minimally-invasive stimulation comprises stimulation from a needle electrode.

13. 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.