TREATMENT OF EXCESS WEIGHT BY NEURAL DOWNREGULATION IN COMBINATION WITH COMPOSITIONS

• US 20090210019A1
• Filed: 02/13/2009
• Published: 08/20/2009
• Est. Priority Date: 02/14/2008
• Status: Active Grant

• Current Assignee: ReShape LifeSciences, Inc.
• Original Assignee: EnteroMedics, Inc. (ReShape LifeSciences, Inc.)
• Inventors: Knudson, Mark B., Kim, Dennis Dong-Won
• Granted Patent: US 9,186,502 B2
• Time in Patent Office: Days
• US Class Current: 607/3
• CPC Class Codes: A61M 2205/3515 using magnetic means
• CPC Class Codes: A61M 2205/3523 using telemetric means
• CPC Class Codes: A61M 2205/353 using mechanical means, e.g. subcutaneous pushbuttons
• CPC Class Codes: A61M 2210/105 Oesophagus
• CPC Class Codes: A61M 2210/1053 Stomach
• CPC Class Codes: A61M 5/14276 specially adapted for implantation
• 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 1/36114 Cardiac control, e.g. by vagal stimulation stimulating the heart A61N1/362
• CPC Class Codes: A61N 1/37223 Circuits for electromagnetic coupling
• CPC Class Codes: A61N 1/37264 Changing the program; Upgrading firmware

Abstract

A method and system for designing a therapy or for treating a condition associated with excess weight in a subject comprising applying a neural conduction block to the vagus nerve at a blocking site with the neural conduction block selected to at least partially block nerve impulses on the vagus nerve at the blocking site and administering a composition comprising an effective amount of an agent that alters the energy balance of the subject.

Claims

1. A system for designing a therapy including a therapy signal and an agent that alters the energy balance of a subject comprising:

at least one electrode configured to be implanted within a body of the patient beneath a skin layer and placed at a vagus nerve, the electrode also configured to apply therapy to the vagus nerve upon application of a therapy signal to the electrode;

an implantable impulse generator for placement in the body of the patient beneath the skin layer, the implantable impulse generator being configured to generate the therapy signal and to transmit the therapy signal to the electrode, the implantable impulse generator being coupled to an implanted antenna;

an external component configured to couple to a first external antenna configured to be placed above the skin layer and adapted to communicate with the implanted antenna across the skin layer through radiofrequency communication, the external component including a plurality of selectable operating modules, each operating module being associated with a different set of operations available for selection by a user;

an external programmer configured to communicatively couple to the external component via a second port, the external programmer being configured to provide therapy instructions comprising parameters for each therapy cycle to the external component, wherein the external component is configured to send the therapy instructions to the implantable impulse generator via the external antenna and the implanted antenna, and the parameters comprise a therapy signal selected to downregulate activity on the vagus nerve with an on time period and off time period, the off time period selected to allow partial recovery of nerve function; and

the external programmer being configured to allow the user to select an agent that alters energy balance in the patient based on the health profile of the patient and the side effects of the agent.

2. The system of claim 1, wherein the selectable operating modules comprise:

an operating room module that is selectable when the external component is coupled to the first external antenna, the operating room module being associated with at least a testing operation to test appropriate positioning of the implantable component within the body;

a therapy delivery module that is selectable when the external component is coupled to a second external antenna, the therapy delivery module being associated with therapy signal generation; and

a diagnostic module that is selectable when the external component is coupled to an external programmer, the programming module being configured to transfer a therapy schedule from the external programmer to the implantable component.

3. The system of claim 1, wherein the implantable component is configured to deliver a therapy cycle comprising an electrical signal having a frequency of at least 300 Hz, an on time of at least 30 seconds, and an off time that allows for partial recovery of the nerve function.

4. The system of claim 1, wherein the external programmer is configured to provide therapy instructions comprising parameters for the therapy cycle to the external component, wherein the parameters of the therapy cycle comprise an electrical signal with a frequency of at least 300 Hz with an on time of at least 30 seconds and an off time that allows partial recovery of nerve function.

5. The system of claim 1, wherein the implantable component is configured to generate therapy signals for a treatment period.

8. The system of claim 4, wherein the external programmer is configured to provide therapy instructions to the external component comprising at least 10 therapy cycles in a treatment period.

10. The system of claim 1, wherein the external programmer is configured to obtain patient data, wherein the patient data comprises data obtained from the implantable component and patient data concerning the health profile of the patient.

11. The system of claim 10, wherein the health profile comprises the presence or absence of conditions selected from the group consisting of diabetes, hypertension, cardiac condition, liver disorder, a renal disorder and combinations thereof.

12. The system of claim 11, wherein the external programmer is configured to obtain data about dosages and side effects of agents that alter energy balance.

13. The system of claim 12, wherein the agents that alter energy balance comprise agents that enhance the sensation of satiety, agents that decrease appetite, agents that block the absorption of fat or other nutrients, agents that inhibit enzymes that digest fat, agents that are thermogenic, or combinations thereof.

14. The system of claim 13, wherein the agents are selected from the group consisting of:

ghrelin, ghrelin agonists, ghrelin antagonists, leptin agonist, leptin antagonists, ciliary neurotrophic factor (CNTF), CNTF analogues, amylin, and amylin analogues.

15. The system of claim 13, wherein the agents are selected from the group consisting of:

sibutramine, fenfluramine, phentermine, dexphenfluoramine, flouxetine, and bupropion.

16. The system of claim 13, wherein the agents are selected from the group consisting of:

sibutramine, leptin, leptin agonists, leptin analogues, CNTF, and CNTF analogues.

17. The system of claim 13, wherein the agents are selected from the group consisting of:

GLP-1, PYY, CKK, and oxyntomodulin.

18. The system of claim 13, wherein the agents are selected from the group consisting of:

phentermine, fenfluramine, dexfenfluramine, endocannabinoid receptor antagonists, ghrelin antagonists, orexin antagonists, somatostatin receptor agonist, GLP-1, PYY, and cholecystokinin agonists.

19. A method for manufacturing a device according to claim 1 comprising:

providing at least one electrode configured to be implanted within a body of the patient beneath a skin layer and placed at a vagus nerve, the electrode also configured to apply therapy to the vagus nerve upon application of a therapy signal to the electrode;

providing an implantable component for placement in the body of the patient beneath the skin layer, the implantable component being coupled to an implanted antenna and the electrode, and configuring the implantable component to generate the therapy signal and to transmit the therapy signal to the electrode;

providing an external component to be placed above the skin layer and adapted to communicate with the implanted antenna across the skin layer through radiofrequency communication, the external component including a plurality of selectable operating modules, each operating module being associated with a different set of operations available for selection by a user and configuring the external component to couple to a first external antenna and to send the therapy instructions to the implantable component via the first external antenna and the implanted antenna;

providing an external programmer and configuring the external programmer to a) communicatively couple to the external component via a second port, b) to provide therapy instructions comprising parameters for each therapy cycle to the external component, wherein the parameters comprise a therapy signal selected to downregulate activity on the vagus nerve with an on time period and off time period, the off time period selected to allow partial recovery of nerve function; and

c) to allow the user to select an agent that alters energy balance in the patient based on the health profile of the patient and the side effects of the agent.

20. The method of claim 19, wherein the implantable component is configured to deliver a therapy cycle comprising an electrical signal having a frequency of at least 300 Hz, an on time of at least 30 seconds, and an off time that allows for partial recovery of the nerve function.

21. The method of claim 19, wherein the external programmer is configured to provide therapy instructions comprising parameters for the therapy cycle to the external component, wherein the parameters of the therapy cycle comprise an electrical signal with a frequency of at least 300 Hz with an on time of at least 30 seconds and an off time that allows partial recovery of nerve function.

22. The method of claim 19, wherein the implantable component is configured to generate therapy signals for a treatment period.

25. The method of claim 21, wherein the external programmer is configured to provide therapy instructions to the external component comprising at least 10 therapy cycles in a treatment period.

26. The method of claim 19, wherein the health profile comprises the presence or absence of conditions selected from the group consisting of diabetes, hypertension, cardiac condition, liver disorder, a renal disorder and combinations thereof.

27. The method of claim 19, further comprising configuring the external programmer to obtain data about dosages and side effects of agents that alter energy balance.

28. The method of claim 27, wherein the agents that alter energy balance comprise agents that enhance the sensation of satiety, agents that decrease appetite, agents that block the absorption of fat or other nutrients, agents that inhibit enzymes that digest fat, agents that are thermogenic, or combinations thereof.

29. A method of selecting parameters for a therapy cycle for an implantable device and of selecting an agent, wherein the therapy cycle and the agent alter energy balance in a subject comprising:

a. selecting parameters of a therapy cycle to be applied to a vagus nerve to provide weight loss to the subject, wherein the parameters comprise an electrical signal having a frequency of 300 Hz or greater, having an on time of at least 30 seconds, and having an off time that allows partial recovery of the nerve;

b. communicating the selected parameters to the implantable device using the system of claim 1 and delivering at least 10 therapy cycles during a treatment period, and

c. selecting an agent and a dosage of agent that alters the energy balance of the subject based on the health profile of the subject and the side effects of the agent using an external programmer of the system of claim 1.

30. The method of claim 29, further comprising selecting the parameters of the therapy cycle based on the body mass index of the subject.

32. The method of claim 29, wherein the health profile of the subject indicates the presence or absence of a condition selected from the group consisting of hypertension, diabetes, cardiac disease, liver disease, renal disease and combinations thereof.

33. The method of claim 29, wherein the side effects of the agent are selected from the group consisting of cardiac arrhythmias, cardiac valve disease, seizures, increased blood pressure, depression, anxiety, diarrhea, increased fat in the stool and combinations thereof.

34. The method of claim 29, wherein the agents that alter energy balance comprise agents that enhance the sensation of satiety, agents that decrease appetite, agents that block the absorption of fat or other nutrients, agents that inhibit enzymes that digest fat, agents that are thermogenic, and combinations thereof.

35. The method of claim 29, wherein communicating the selected parameters using the system of claim 1 comprises communicating the selected parameters from the external programmer to the external component, and communicating the selected parameters from the external component to the implantable device.

36. The method of claim 35, wherein the external programmer is configured to obtain patient data, wherein the patient data comprises data obtained from the implantable component and data concerning the health profile of the patient.

37. The method of claim 29, wherein the external programmer is configured to obtain data about dosages and side effects of agents that alter energy balance.

6-7. -7. (canceled)

9. (canceled)

23-24. -24. (canceled)

31. (canceled)

38. A method of applying a treatment to a vagus nerve in a subject comprising:

applying multiple therapy cycles to a vagus nerve during a treatment period, wherein each therapy cycle comprises an electrical signal having parameters selected to provide weight loss to the subject, wherein the parameters comprise a frequency, an on period, and an off period, wherein the frequency and the on period of the electrical signal are selected to down-regulate neural activity on the nerve, and the off period is selected to allow partial restoration of neural activity; and

administering a composition comprising an effective amount of an agent that alters the energy balance of the subject.

39. The method according to claim 38, wherein the frequency of the electrical signal is at least 300 Hz.

40. The method according to claim 38, wherein the on time of the signal is greater than 30 seconds.

41. The method according to claim 38, wherein the off time of the signal is at least 1 minute.

42. The method according to claim 38, wherein the treatment period is at least eight hours.

43. The method according to claim 38, wherein at least 10 therapy cycles are applied to the vagus nerve during the treatment period.

47. The method according to claim 38, wherein the electrical signal is applied to the vagus nerve at a location near or distal to a diaphragm of the subject.

48. The method according to claim 38, wherein the agent that changes an energy balance in the subject is an anorexic agent.

49. The method according to claim 48, wherein the anorexic agent is selected from the group consisting of phentermine, fenfluramine, dexfenfluramine, endocannabinoid receptor antagonists, ghrelin antagonists, orexin antagonists, and cholecystokinin agonists.

50. The method according to claim 38, wherein the agent that changes an energy balance in the subject is a thermogenic agent.

51. The method according to claim 50, wherein the thermogenic agent is selected from the group consisting of sibutramine, leptin, leptin agonist, a leptin variant, CNTF, and a CNTF variant.

52. The method according to claim 38, wherein the agent that changes the energy balance in the subject is an agent that inhibits fat absorption.

53. The method according to claim 52, wherein agent that inhibits fat absorption is orlistat or a lipin inhibitor.

54. The method according to claim 38, wherein the agent that changes an energy balance in the subject is an agent that enhances satiety.

55. The method according to claim 54, wherein the agent that enhances satiety is selected from the group consisting of somatostatin receptor antagonist, GLP-1 agonists, GLP-1 variants, peptide PYY, POMC agonists, neuropeptide Y inhibitors, topiramate, bupropion, naltrexone, zonisamide, amylin, amylin variants, and oxyntomodulin.

44-46. -46. (canceled)

56. A treatment comprising:

selecting a drug for treating obesity for a patient where effective dosages for treating obesity for such a patient are associated with disagreeable side effects contributing to said patient not complying with a drug treatment; and

treating a patient for obesity with a concurrent treatment comprising;

a) applying an intermittent neural block to a vagus nerve of the patient at multiple times per day and over multiple days with the block selected to down-regulate afferent and/or efferent neural activity on the nerve and with neural activity restoring upon discontinuance of said block; and

b) administering said drug to the patient at a dosage less than said recommended dosage.