Methods and systems for glucose regulation

• US 8,483,830 B2
• Filed: 04/03/2009
• Issued: 07/09/2013
• Est. Priority Date: 04/04/2008
• Status: Active Grant

• Current Assignee: ReShape LifeSciences, Inc.
• Original Assignee: EnteroMedics, Inc. (ReShape LifeSciences, Inc.)
• Inventors: Tweden, Katherine S., Knudson, Mark B., Wilson, Richard R., Thornton, Arnold W., Kim, Dennis Dong-won
• Primary Examiner(s): DIETRICH, JOSEPH M
• Application Number:
  US12/417,918
• Publication Number:
  US 20090254143A1
• Time in Patent Office: 1,558 Days
• Field of Search: 607/40, 607/41, 607/133
• US Class Current: 607/40
• CPC Class Codes: A61M 5/00 Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests vaccination appliances for veterinary use A61D1/025 ; tube connectors, tube couplings, valves or branch units specially adapted for medical use A61M39/00; containers specially adapted for medical or pharmaceutical purposes A61J1/00; combinations of vial and syringe for mixing or transferring their contents A61J1/20; holders for containers for collecting, storing or administering blood or medical fluids A61J1/16
• CPC Class Codes: A61N 1/0551 Spinal or peripheral nerve electrodes
• CPC Class Codes: A61N 1/36007 of urogenital or gastrointestinal organs, e.g. for incontinence control
• CPC Class Codes: A61N 1/36053 adapted for vagal stimulation A61N1/36114 takes precedence
• CPC Class Codes: A61N 1/36167 Timing, e.g. stimulation onset
• CPC Class Codes: A61N 1/37211 Means for communicating with stimulators
• CPC Class Codes: A61N 1/37235 Aspects of the external programmer

Abstract

Various methods and apparatus for treating a condition associated with impaired glucose regulation in a subject comprising in one embodiment, applying a neural conduction block to a target nerve at a blocking site with the neural conduction block selected to at least partially block nerve pulses. In another embodiment, combinations of down-regulating and or up-regulating with or without pharmaceutical agents are used to treat impaired glucose regulation. In other embodiments, up-regulation or down-regulation of various nerves, such as the vagus and its branches, and the splanchnic is used to modify the production of GLP-1 and GIP, thereby controlling glucose levels. In yet further embodiments, combinations of down-regulating and or up-regulating with or without pharmaceutical agents are used to modify the production of GLP-1 and GIP, to treat impaired glucose regulation.

Claims

1. A system for treating a patient with impaired glucose regulation comprising:

at least two electrodes operably connected to an implantable pulse generator, wherein one of the electrodes is adapted to be placed on a vagus nerve below a vagal innervation of the heart;

an implantable pulse generator that comprises a power module and a programmable therapy delivery module, wherein the programmable therapy delivery module is configured to deliver at least one therapy program comprising an electrical signal treatment applied intermittently multiple times in a day and over multiple days to the vagus nerve, wherein the electrical signal treatment is selected to reduce a HbA1C %, has a frequency selected to downregulate activity on the vagus nerve of at least 500 Hz, an on time and an off time, wherein the off time is selected to allow at least a partial recovery of the activity of the vagus nerve; and

an external component comprising an antenna and a programmable storage and communication module, wherein programmable storage and communication module is configured to store the at least one therapy program and to communicate the at least one therapy program to the implantable pulse generator.

2. The system of claim 1, wherein the at least one electrode is adapted to be placed on an organ selected from the spleen, stomach, duodenum, pancreas and ileum.

3. The system of claim 1, wherein the at least one electrode is adapted to be placed on a second target nerve selected from a splanchnic nerve, a hepatic branch of the vagus nerve, a celiac branch of a vagus nerve and combinations thereof.

4. The system of claim 1, wherein the programmable therapy delivery module is configured to deliver an electrical signal having a frequency of at least 500 to 5000 Hz.

5. The system of claim 1, wherein the programmable therapy delivery module is configured to deliver an electrical signal having an on time of about 30 seconds to 5 minutes.

6. The system of claim 5, wherein the programmable therapy delivery module is configured to deliver an electrical signal having an off time of about 5 to 30 minutes.

7. The system of claim 1, wherein the programmable storage and communication module is configured to deliver a therapy program to the implantable pulse generator, wherein the program comprises an electrical signal treatment applied intermittently multiple times in a day and over multiple days, wherein the electrical signal treatment is selected to reduce a HbA 1C %, has a frequency selected to down-regulate activity on the vagus nerve of at least 500 Hz, and has an on time and an off time, wherein the off time is selected to allow at least a partial recovery of the activity of the vagus nerve.

8. The system of claim 1, wherein the programmable storage and communication module is configured to store and communicate more than one therapy program, wherein each therapy program is different from one another, and is configured to be selected for communication.

9. The system of claim 1, wherein programmable therapy delivery module is configured to deliver a second therapy program comprising an electrical signal treatment applied intermittently multiple times in a day and over multiple days to a second target nerve or organ, wherein the electrical signal has a frequency selected to upregulate or down-regulate activity on the second target nerve or organ and has an on time and an off time, wherein the off time is selected to allow at least a partial recovery of the activity of the second target nerve or organ to baseline levels.

10. The system of claim 9, wherein the second target nerve is the splanchnic nerve or the celiac branch of the vagus nerve.

11. The system of claim 9, wherein the second target organ is the duodenum or ileum.

12. The system of claim 1, further comprising a sensor operable connected to the implantable pulse generator.

13. The system of claim 12, wherein the sensor detects an increase or decrease of blood glucose from a threshold level.

14. The system of claim 12, wherein the programmable therapy delivery module is configured to deliver the second therapy program in response to a signal from the sensor.

15. The system of claim 9, wherein the upregulating signal has a frequency of less than 200 Hz.

16. The system of claim 15, wherein the on time is about 30 seconds to 15 minutes.

17. The system of claim 15, wherein the off time is about 5 to 45 minutes.

18. A method of treating a condition associated with impaired glucose regulation in a subject comprising:

Treating the subject by applying an intermittent electrical signal to a vagus nerve below a vagal innervation of the heart of the subject having impaired glucose regulation using the system of claim 1, with said electrical signal treatment selected to reduce a HbA1C %, and selected to down-regulate neural activity on the vagus nerve with a frequency of at least 500 Hz, and to restore neural activity on the vagus nerve upon discontinuance of said signal.

19. The method according to claim 18, wherein the condition is type 2 diabetes.

20. The method of claim 18, wherein the electrical signal is applied intermittently in a cycle including an on time of application of the signal followed by an off time during which the signal is not applied to the nerve, wherein the on and off times are applied multiple times per day over multiple days.

21. The method of claim 20, wherein the on time is selected to have a duration of about 30 seconds up to about 5 minutes.

22. The method according to claim 18, wherein the electrical signal is applied at a frequency of about 500 Hz to 5000 Hz.

23. The method according to claim 18, wherein the electrical signal is applied on the hepatic branch of the vagus nerve.

24. The method according to claim 18, wherein the electrical signal is applied on the celiac branch of the vagus nerve.

25. The method according to claim 18, wherein the electrical signal is applied to the liver, duodenum, jejunum, ileum, or combinations thereof.

26. The method of claim 18, further comprising applying an upregulating signal to a second target nerve or organ.

27. The method of claim 26, wherein the downregulating and upregulating signals are applied at the same time or different time.

28. The method of claim 26, wherein the second target nerve is the splanchnic nerve.

29. The method of claim 26, wherein the second target organ is the duodenum or ileum.

30. The method according to claim 18, further comprising administering an agent that improves glucose control.

31. The method of claim 30, wherein the agent increases the amount of insulin and/or increases the sensitivity of cells to insulin.

32. The method of claim 31, wherein the agent that increases the amount of insulin is selected from the group consisting of insulin, insulin analogs, sulfonylureas, meglitinides, GLP-1 analogs, and DPP4 inhibitors.

33. The method of claim 31, wherein the agent that increases the sensitivity of cells to insulin is a PPAR alpha, gamma, or delta agonist.

34. A diabetes or prediabetes treatment comprising:

i) selecting a drug for treating diabetes or impaired glucose control for a patient where effective dosages for treating diabetes or prediabetes for such a patient are associated with disagreeable side effects or impaired glycemic control; and

ii) treating a patient for diabetes or impaired glucose control with a concurrent treatment comprising;

a) applying an intermittent electrical signal treatment using a system of claim 1 to a vagus nerve below a vagal innervation of the heart of the patient at multiple times per day and over multiple days, wherein the electrical signal treatment is selected to reduce a HbA1C %, and selected to down-regulate afferent and efferent neural activity on the vagus nerve with a frequency of at least 500 Hz, and with neural activity restoring upon discontinuance of said block; and

b) administering said drug to the patient.

35. A method of making a system for treating a patient with impaired glucose regulation comprising:

providing at least two electrodes operably connectable to an implantable pulse generator, wherein one of the electrodes is adapted to be placed on a vagus nerve below a vagal innervation of the heart;

configuring a programmable therapy delivery module of the implantable pulse generator to deliver at least one therapy program comprising an electrical signal treatment applied intermittently multiple times in a day and over multiple days to the vagus nerve, wherein the electrical signal treatment is selected to reduce a HbA1C %, has a frequency selected to downregulate activity on the vagus nerve of at least 500 Hz, and has an on time and an off time, wherein the off time is selected to allow at least a partial recovery of the activity of the vagus nerve; and

configuring a programmable storage and communication module of an external component to store the at least one therapy program and to communicate the at least one therapy program to the implantable pulse generator.

36. The method of claim 35, further comprising

configuring the programmable therapy delivery module of the implantable pulse generator to deliver the second therapy program comprising an electrical signal treatment applied intermittently multiple times in a day and over multiple days to a second target nerve or organ, wherein the electrical signal has a frequency selected to upregulate or down-regulate activity on the second target nerve or organ and has an on time and an off time, wherein the off time is selected to allow at least a partial recovery of the activity of the second target nerve or organ to baseline levels.

37. The method of claim 35, further comprising providing a sensor to the implantable pulse generator.

38. The method of claim 35, further comprising configuring the programmable therapy delivery module of the implantable pulse generator to deliver the second therapy program upon a signal from the sensor.