Nerve stimulation for treatment of obesity, metabolic syndrome, and type 2 diabetes

• US 20070203521A1
• Filed: 01/24/2007
• Published: 08/30/2007
• Est. Priority Date: 03/22/2002
• Status: Active Grant

• Current Assignee: Advanced Neuromodulation Systems Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Leptos Biomedical, Inc. (Abbott Laboratories Incorporated)
• Inventors: Neisz, Hans, Dobak, John
• Granted Patent: US 7,702,386 B2
• Time in Patent Office: Days
• US Class Current: 607/2
• CPC Class Codes: A61N 1/36007 of urogenital or gastrointestinal organs, e.g. for incontinence control
• CPC Class Codes: A61N 1/36085 Eating disorders or obesity
• CPC Class Codes: A61N 1/36117 for treating hypertension

Abstract

A tissue modulation device, for treating at least one of obesity, metabolic syndrome, and Type 2 diabetes in a patient, is described. In some embodiments, the device includes a storage module having computer-readable instructions for delivering an electrical stimulation pattern to a splanchnic nerve of the patient. The stimulation pattern includes at least one on-time. The on-time includes at least one of a suprathreshold period and a subthreshold period. The splanchnic nerve is selected from the group consisting of the greater splanchnic nerve, the lesser splanchnic nerve, and the least splanchnic nerve. The pattern is effective to ameliorate at least one attendant condition of obesity, metabolic syndrome, and Type 2 diabetes in the patient. The attendant condition includes dyslipidemia, hypertension, hyperinsulinemia, hyperglycemia, and/or insulin resistance.

Claims

1. A method, for treating at least one of obesity, Type 2 diabetes, and metabolic syndrome in a patient, comprising:

providing a pulse generator, the pulse generator having a programmable stimulation pattern with a signal-on time that comprises a subthreshold period and a suprathreshold period;

electrically activating a splanchnic nerve of a patient with the pulse generator, using the stimulation pattern, so as to ameliorate or eliminate an attendant condition of the at least one of obesity, metabolic syndrome, and Type 2 diabetes in the patient, the attendant condition comprising at least one of dyslipidemia, hypertension, hyperinsulinemia, hyperglycemia, and insulin resistance, wherein the splanchnic nerve is selected from the group consisting of the greater splanchnic nerve, the lesser splanchnic nerve, and the least splanchnic nerve.

2. The method of claim 1, further comprising programming the stimulation pattern so as to keep the patient'"'"'s blood pressure within safe limits.

3. The method of claim 1, wherein the subthreshold period is zero or about zero seconds.

4. The method of claim 1, wherein the stimulation pattern comprises a stimulation intensity;

and

the stimulation intensity is between about 0.005 and about 5.0 mA-msec.

5. The method of claim 1, wherein the stimulation pattern comprises a frequency, a pulse width, and a current;

and

wherein the frequency is between about 0.1 Hz and about 50 Hz;

the pulse width is between about 100 microseconds and about 1 millisecond; and

the current is between about 0.1 mA and about 10 mA.

6. The method of claim 1, wherein the stimulation pattern comprises an signal-on time and an off time;

and

wherein the off time is no less than the signal-on time.

7. The method of claim 1, wherein the stimulation pattern comprises a substantially continuous signal-on time, wherein the signal-on time is comprised of at least one suprathreshold period and at least one subthreshold period.

8. The method of claim 7, wherein the subthreshold period is no less than the suprathreshold period.

9. The method of claim 7, wherein the suprathreshold period is greater than the subthreshold period.

10. The method of claim 1, further comprising:

providing a first electrical signal to the splanchnic nerve at a first stimulation intensity during a first portion of a first stimulation period, the stimulation period comprising at least one on-time, the on-time comprising at least one of a suprathreshold period and a subthreshold period;

applying a second electrical signal to the splanchnic nerve at a second stimulation intensity during a second portion of the first stimulation period;

ceasing or substantially reducing the applying of the second signal during a first no-stimulation period;

thereafter, applying a third electrical signal to the splanchnic nerve at a third stimulation intensity during a first portion of a second stimulation period, the stimulation period comprising at least one on-time, the on-time comprising at least one of a suprathreshold period and a subthreshold period;

applying a fourth electrical signal to the splanchnic nerve at a fourth stimulation intensity during a second portion of the second stimulation period; and

ceasing or substantially reducing the applying of the fourth signal during a second no-stimulation period.

11. The method of claim 9, wherein the second stimulation intensity is greater than the first stimulation intensity.

12. The method of claim 9, wherein the fourth stimulation intensity is greater than the third stimulation intensity.

13. The method of claim 9, wherein the second stimulation intensity is greater than the first stimulation intensity, and the fourth stimulation intensity is greater than the third stimulation intensity.

14. The method of claim 9, wherein the third stimulation intensity is approximately equal to the first stimulation intensity.

15. The method of claim 9, wherein the duration of the first no-stimulation period is approximately equal to the duration of the second no-stimulation period.

16. The method of claim 9, wherein the duration of the first stimulation period is approximately equal to the duration of the second stimulation period.

17. The method of claim 9, wherein the duration of the first portion of the first stimulation period is approximately equal to the duration of the second portion of the first stimulation period.

18. The method of claim 9, wherein the duration of the first portion of the second stimulation period is approximately equal to the duration of the second portion of the second stimulation period.

19. The method of claim 1, further comprising:

applying a first plurality of temporally sequential electrical signals during a first plurality of respective stimulation periods, each of the first plurality of signals having a stimulation intensity that is greater than the stimulation intensity of the preceding signal, each stimulation period comprising at least one on-time, the on-time comprising at least one of a suprathreshold period and a subthreshold period;

thereafter, ceasing or substantially reducing electrical stimulation to the splanchnic nerve during a first no-stimulation period;

thereafter, applying a second plurality of temporally sequential electrical signals during a second plurality of respective stimulation periods, each of the second plurality of signals having a stimulation intensity that is greater than the stimulation intensity of the preceding signal, each stimulation period comprising at least one on-time, the on-time comprising at least one of a suprathreshold period and a subthreshold period; and

thereafter, ceasing or substantially reducing electrical stimulation to the splanchnic nerve during a second no-stimulation period.

20. The method of claim 1, further comprising:

electrically stimulating the splanchnic nerve for a first time and at a first stimulation intensity during a first stimulation period, the stimulation period comprising at least one on-time, the on-time comprising at least one of a suprathreshold period and a subthreshold period;

thereafter, electrically stimulating the splanchnic nerve for a second time and at a second stimulation intensity during the first stimulation period, the second stimulation intensity being greater than the first stimulation intensity; and

thereafter, providing a second period during which electrical stimulation at the splanchnic nerve is absent or substantially less than the second stimulation intensity.

21. The method of claim 1, wherein the attendant condition comprises dyslipidemia.

22. The method of claim 21, wherein the dyslipidemia comprises decreased HDL.

23. The method of claim 21, wherein the dyslipidemia comprises elevated triglycerides.

24. The method of claim 21, wherein the dyslipidemia comprises elevated LDL.

25. The method of claim 1, wherein the attendant condition comprises an elevated blood pressure.

26. The method of claim 1, wherein the attendant condition comprises hyperglycemia.

27. The method of claim 1, wherein the attendant condition comprises hyperinsulinemia.

28. The method of claim 1, wherein the attendant condition comprises insulin resistance.

29. A method, to increase lean muscle mass of a patient, comprising electrically modulating a sympathetic nerve of a patient in a stimulation pattern effective to increase a lean muscle mass of the patient, wherein the stimulation pattern comprises at least one on-time, the on-time comprising at least one of a suprathreshold period and a subthreshold period.

30. The method of claim 29, wherein a splanchnic nerve of the patient comprises the sympathetic nerve, and wherein the splanchnic nerve is selected from the group consisting of the greater splanchnic nerve, the lesser splanchnic nerve, and the least splanchnic nerve.

31. The method of claim 29, wherein the stimulation pattern comprises a frequency, a pulse width, and a current;

and

wherein the frequency is between about 0.1 Hz and about 50 Hz;

the pulse width is between about 100 microseconds and about 1 millisecond; and

the current is between about 0.1 mA and about 10 mA.

32. A method of stimulating a splanchnic nerve in a mammal, the method comprising the following steps:

1) electrically stimulating the splanchnic nerve for a first time and at a first stimulation intensity during a first stimulation period, the stimulation period comprising at least one on-time, the on-time comprising at least one of a suprathreshold period and a subthreshold period, wherein the splanchnic nerve is selected from the group consisting of the greater splanchnic nerve, the lesser splanchnic nerve, and the least splanchnic nerve;

2) thereafter, electrically simulating the splanchnic nerve for a second time and at a second stimulation intensity during the first stimulation period, the second stimulation intensity being greater than the first stimulation intensity;

3) thereafter, providing a second period during which electrical stimulation at the splanchnic nerve is less than the first stimulation intensity.

33. The method of claim 32, wherein the subthreshold period is zero or about zero seconds.

34. The method of claim 32, further comprising repeating steps 1-3.

35. The method of claim 32, wherein a duration of the second period is configured to minimize weight gain or maximize weight loss in the mammal during the period.

36. The method of claim 32, further comprising electrically stimulating the splanchnic nerve at least one additional time between the first time and the second time during the first stimulation period.

37. The method of claim 32, wherein the second stimulation intensity is about 1% to about 10,000% greater than the first stimulation intensity.

38. The method of claim 32, wherein the second stimulation intensity is about 2% to about 1,000% greater than the first stimulation intensity.

39. The method of claim 32, wherein the second stimulation intensity is about 4% to about 500% greater than the first stimulation intensity.

40. The method of claim 32, wherein the second stimulation intensity is about 8% to about 100% greater than the first stimulation intensity.

41. The method of claim 32, wherein the second stimulation intensity is about 10% to about 50% greater than the first stimulation intensity.

42. The method of claim 32, wherein the second stimulation intensity is about 15% to about 30% greater than the first stimulation intensity.

43. The method of claim 32, wherein the second stimulation intensity is about 20% greater than the first stimulation intensity.

44. The method of claim 32, wherein the first stimulation intensity is about equal to the threshold for skeletal muscle twitch in the mammal.

45. The method of claim 32, wherein the mammal is a human.

46. The method of claim 32, wherein the first time is between about 30 seconds and about 300 days.

47. The method of claim 32, wherein the first time is between about one minute and about 100 days.

48. The method of claim 32, wherein the first time is between about five minutes and about 50 days.

49. The method of claim 32, wherein the first time is between about 30 minutes and about 30 days.

50. The method of claim 32, wherein the first time is between about one hour and about seven days.

51. The method of claim 32, wherein the first time is between about four hours and about four days.

52. The method of claim 32, wherein the first time is between about six hours and about 36 hours.

53. The method of claim 32, wherein the first time is between about 20 hours and about 28 hours.

54. The method of claim 32, wherein the first time is about 24 hours.

55. The method of claim 32, wherein the second time is between about 30 seconds and about 300 days.

56. The method of claim 32, wherein the second time is between about one minute and about 100 days.

57. The method of claim 32, wherein the second time is between about five minutes and about 50 days.

58. The method of claim 32, wherein the second time is between about 30 minutes and about 30 days.

59. The method of claim 32, wherein the second time is between about one hour and about seven days.

60. The method of claim 32, wherein the second time is between about four hours and about four days.

61. The method of claim 32, wherein the second time is between about six hours and about 36 hours.

62. The method of claim 32, wherein the second time is between about 20 hours and about 28 hours.

63. The method of claim 32, wherein the second time is about 24 hours.

64. The method of claim 32, wherein the first time is approximately equal to the second time.

65. The method of claim 32, wherein the second period is between about 30 seconds and about 300 days.

66. The method of claim 32, wherein the second period is between about one minute and about 100 days.

67. The method of claim 32, wherein the second period is between about five minutes and about 50 days.

68. The method of claim 32, wherein the second period is between about 30 minutes and about 30 days.

69. The method of claim 32, wherein the second period is between about one hour and about 15 days.

70. The method of claim 32, wherein the second period is between about one day and about ten days.

71. The method of claim 32, wherein the second period is between about two days and about seven days.

72. The method of claim 32, wherein the second period is between about three days and about five days.

73. The method of claim 32, wherein the second period is about four days.

74. An implantable pulse generator programmed to modulate electrically a splanchnic nerve in a mammal, in the following sequence:

providing a first electrical signal to the splanchnic nerve at a first stimulation intensity during a first portion of a first stimulation period, the first stimulation period comprising at least one on-time, the on-time comprising at least one of a suprathreshold period and a subthreshold period, wherein the splanchnic nerve is selected from the group consisting of the greater splanchnic nerve, the lesser splanchnic nerve, and the least splanchnic nerve;

providing a second electrical signal to the splanchnic nerve at a second stimulation intensity during a second portion of a first stimulation period;

ceasing or substantially reducing the providing of the second signal during a first no-stimulation period;

thereafter providing a third electrical signal to the splanchnic nerve at a third stimulation intensity during a first portion of a second stimulation period, the second stimulation period comprising at least one on-time, the on-time comprising at least one of a suprathreshold period and a subthreshold period;

providing a fourth electrical signal to the splanchnic nerve at a fourth stimulation intensity during a second portion of a second stimulation period;

ceasing or substantially reducing the providing of the fourth signal during a second no-stimulation period.

75. The implantable pulse generator of claim 74, further configured such that the second stimulation intensity is greater than the first stimulation intensity, and the fourth stimulation intensity is greater than the third stimulation intensity.

76. An implantable pulse generator programmed to modulate electrically a splanchnic nerve in a mammal, in the following sequence of steps:

1) electrically stimulating the splanchnic nerve for a first time and at a first stimulation intensity during a stimulation period, the stimulation period comprising at least one on-time, the on-time comprising at least one of a suprathreshold period and a subthreshold period, wherein the splanchnic nerve is selected from the group consisting of the greater splanchnic nerve, the lesser splanchnic nerve, and the least splanchnic nerve;

2) thereafter, electrically simulating the splanchnic nerve for a second time and at a second stimulation intensity during the first stimulation period, the second stimulation intensity being greater than the first stimulation intensity;

3) thereafter, providing a second period during which electrical stimulation at the splanchnic nerve is absent or substantially less than the second stimulation intensity.

77. The implantable pulse generator of claim 76, wherein the subthreshold period is zero or about zero seconds.

78. The implantable pulse generator of claim 76, further programmed to repeat steps 1-3.

79. The implantable pulse generator of claim 76, further programmed such that the second stimulation intensity is greater than the first stimulation intensity.

80. The implantable pulse generator of claim 76, further programmed such that the second stimulation intensity is about 20% greater than the first stimulation intensity.

81. The implantable pulse generator of claim 76, further programmed such that the first time is between about four hours and about four days.

82. The implantable pulse generator of claim 76, further programmed such that the second time is between about four hours and about four days.

83. The implantable pulse generator of claim 76, further programmed such that the period is between about two days and about seven days.

84. The implantable pulse generator of claim 76, wherein the implantable pulse generator is programmed in hardware to modulate the splanchnic nerve.

85. The implantable pulse generator of claim 76, wherein the implantable pulse generator is programmed in software to modulate the splanchnic nerve.

86. A tissue modulation device, for treating at least one of obesity, metabolic syndrome, and Type 2 diabetes in a patient, comprising:

a storage module having computer-readable instructions for delivering an electrical stimulation pattern to a splanchnic nerve of the patient, wherein the stimulation pattern comprises at least one on-time, the on-time comprising at least one of a suprathreshold period and a subthreshold period, and wherein the splanchnic nerve is selected from the group consisting of the greater splanchnic nerve, the lesser splanchnic nerve, and the least splanchnic nerve;

the pattern being effective to ameliorate at least one attendant condition of the at least one of obesity, metabolic syndrome, and Type 2 diabetes in the patient; and

the attendant condition comprising at least one of dyslipidemia, hypertension, hyperinsulinemia, hyperglycemia, and insulin resistance.

87. The device of claim 86, further comprising:

an energy delivery module that is electrically coupled to the storage module;

wherein the energy delivery module is configured to deliver electrical energy to the splanchnic nerve of the patient according to the instructions.

88. The device of claim 86, wherein an implantable pulse generator comprises the storage module.

89. A tissue modulation device comprising:

a storage module having computer-readable instructions for delivering an electrical stimulation pattern to a splanchnic nerve, wherein the stimulation pattern comprises at least one on-time, the on-time comprising at least one of a suprathreshold period and a subthreshold period, and wherein the splanchnic nerve is selected from the group consisting of the greater splanchnic nerve, the lesser splanchnic nerve, and the least splanchnic nerve;

the pattern being effective to result in an increase in the patient'"'"'s lean muscle mass.

90. The device of claim 89, further comprising:

an energy delivery module that is electrically coupled to the storage module;

wherein the energy delivery module is configured to deliver electrical energy to the splanchnic nerve of the patient according to the instructions.

92. The device of claim 89, further comprising:

means for delivering electrical energy to the splanchnic nerve of the patient in the pattern according to the instructions;

the means for delivering electrical energy being electrically coupled to the storage module.

91. A tissue modulation device, for treating at least one of obesity, metabolic syndrome, and Type 2 diabetes in a patient, comprising:

means for storing computer-readable instructions for delivering an electrical stimulation pattern to a splanchnic nerve of the patient, wherein the stimulation pattern comprises at least one on-time, the on-time comprising at least one of a suprathreshold period and a subthreshold period, and wherein the splanchnic nerve is selected from the group consisting of the greater splanchnic nerve, the lesser splanchnic nerve, and the least splanchnic nerve;

the pattern being effective to ameliorate at least one attendant condition of the at least one of obesity, metabolic syndrome, and Type 2 diabetes in the patient; and

the attendant condition comprising at least one of dyslipidemia, hypertension, hyperinsulinemia, hyperglycemia, and insulin resistance.

93. A tissue modulation device comprising:

means for storing computer-readable instructions for delivering an electrical stimulation pattern to a splanchnic nerve of the patient, wherein the stimulation pattern comprises at least one on-time, the on-time comprising at least one of a suprathreshold period and a subthreshold period, and wherein the splanchnic nerve is selected from the group consisting of the greater splanchnic nerve, the lesser splanchnic nerve, and the least splanchnic nerve;

the pattern being effective to result in an increase in the patient'"'"'s lean muscle mass.

94. The device of claim 93, further comprising:

means for delivering electrical energy to the splanchnic nerve of the patient in the pattern according to the instructions;

the means for delivering electrical energy being electrically coupled to the storage module.

95. A method, to increase a concentration of HDL in a patient, comprising:

electrically modulating a sympathetic nerve of a patient in a stimulation pattern, wherein the stimulation pattern comprises at least one on-time, the on-time comprising at least one of a suprathreshold period and a subthreshold period;

the pattern being effective to increase the concentration of HDL of the patient.

96. The method of claim 95, wherein a splanchnic nerve comprises the sympathetic nerve, and wherein the splanchnic nerve is selected from the group consisting of the greater splanchnic nerve, the lesser splanchnic nerve, and the least splanchnic nerve.

97. A method, to decrease a concentration of LDL in a patient, comprising:

electrically modulating a sympathetic nerve of a patient in a stimulation pattern, wherein the stimulation pattern comprises at least one on-time, the on-time comprising at least one of a suprathreshold period and a subthreshold period;

the pattern being effective to decrease the concentration of LDL in the patient.

98. The method of claim 97, wherein a splanchnic nerve comprises the sympathetic nerve, and wherein the splanchnic nerve is selected from the group consisting of the greater splanchnic nerve, the lesser splanchnic nerve, and the least splanchnic nerve.

99. A method, to decrease a concentration of serum cholesterol in a patient, comprising:

electrically modulating a sympathetic nerve of a patient in a stimulation pattern, wherein the stimulation pattern comprises at least one on-time, the on-time comprising at least one of a suprathreshold period and a subthreshold period;

the pattern being effective to decrease the concentration of serum cholesterol in the patient.

100. The method of claim 99, wherein a splanchnic nerve comprises the sympathetic nerve, and wherein the splanchnic nerve is selected from the group consisting of the greater splanchnic nerve, the lesser splanchnic nerve, and the least splanchnic nerve.

101. A method, to reduce a concentration of serum triglycerides in a patient, comprising:

electrically modulating a sympathetic nerve of a patient in a stimulation pattern, wherein the stimulation pattern comprises at least one on-time, the on-time comprising at least one of a suprathreshold period and a subthreshold period;

the pattern being effective to reduce the concentration of serum triglycerides in the patient.

102. The method of claim 101, wherein a splanchnic nerve comprises the sympathetic nerve, wherein the splanchnic nerve is selected from the group consisting of the greater splanchnic nerve, the lesser splanchnic nerve, and the least splanchnic nerve.

103. A method, to treat hypertension in a patient, comprising:

electrically modulating a sympathetic nerve of a patient in a stimulation pattern, wherein the stimulation pattern comprises at least one on-time, the on-time comprising at least one of a suprathreshold period and a subthreshold period;

the pattern being effective to lower a blood pressure in the patient.

104. A tissue modulation device, for treating hypertension in a patient, comprising:

means for storing computer-readable instructions for electrically modulating a splanchnic nerve of a patient in a stimulation pattern, wherein the stimulation pattern comprises at least one on-time, the on-time comprising at least one of a suprathreshold period and a subthreshold period, and wherein the splanchnic nerve is selected from the group consisting of the greater splanchnic nerve, the lesser splanchnic nerve, and the least splanchnic nerve;

the pattern being effective to lower a blood pressure in the patient.

106. The method of claim 104, wherein the stimulation pattern is effective to result in an increase in the patient'"'"'s lean muscle mass.

105. A method, of treating at least one of obesity, metabolic syndrome, and Type 2 diabetes, comprising:

electrically modulating a splanchnic nerve of a patient in a stimulation pattern that ameliorates or eliminates an attendant condition of the at least one of obesity, metabolic syndrome, and Type 2 diabetes, without causing significant net weight loss in a patient;

the attendant condition comprising at least one of dyslipidemia, hypertension, hyperinsulinemia, hyperglycemia, and insulin resistance;

wherein the stimulation pattern comprises at least one on-time, the on-time comprising at least one of a suprathreshold period and a subthreshold period; and

wherein the splanchnic nerve is selected from the group consisting of the greater splanchnic nerve, the lesser splanchnic nerve, and the least splanchnic nerve.

107. A tissue modulation device, for treating at least one of obesity, metabolic syndrome, and Type 2 diabetes in a patient, comprising:

means for storing computer-readable instructions for delivering an electrical stimulation pattern to a splanchnic nerve of the patient, wherein the stimulation pattern comprises at least one on-time, the on-time comprising at least one of a suprathreshold period and a subthreshold period, and wherein the splanchnic nerve is selected from the group consisting of the greater splanchnic nerve, the lesser splanchnic nerve, and the least splanchnic nerve;

the pattern being effective to ameliorate at least one attendant condition of the at least one of obesity, metabolic syndrome, and Type 2 diabetes in the patient, without causing significant net weight loss; and

the attendant condition comprising at least one of dyslipidemia, hypertension, hyperinsulinemia, hyperglycemia, and insulin resistance.

108. The device of claim 107, wherein the stimulation pattern is effective to result in an increase in the patient'"'"'s lean muscle mass.