Device and implantation system for electrical stimulation of biological systems

• US 8,712,530 B2
• Filed: 03/04/2011
• Issued: 04/29/2014
• Est. Priority Date: 03/05/2010
• Status: Active Grant

• Current Assignee: Paras Holdings LLC
• Original Assignee: EndoStim, Inc.
• Inventors: Sharma, Virender K., Gani, Matthew Joseph, Goode, Paul V., Hogg, Bevil, Miazga, Jay, Policker, Shai, Raby, Kaila
• Primary Examiner(s): DIETRICH, JOSEPH M
• Application Number:
  US13/041,114
• Publication Number:
  US 20110307028A1
• Time in Patent Office: 1,152 Days
• Field of Search: 607/40
• US Class Current: 607/40
• CPC Class Codes: A61B 5/0031 Implanted circuitry
• CPC Class Codes: A61B 5/037 Measuring oesophageal pressure
• CPC Class Codes: A61B 5/0538 invasively, e.g. using a catheter
• CPC Class Codes: A61B 5/1116 Determining posture transitions
• CPC Class Codes: A61B 5/14539 for measuring pH
• CPC Class Codes: A61B 5/4211 Diagnosing or evaluating reflux
• CPC Class Codes: A61B 5/4836 Diagnosis combined with treatment in closed-loop systems or methods A61B5/0036 takes precedence
• CPC Class Codes: A61N 1/36007 of urogenital or gastrointestinal organs, e.g. for incontinence control
• CPC Class Codes: A61N 1/3606 adapted for a particular treatment
• CPC Class Codes: A61N 1/36139 with automatic adjustment
• CPC Class Codes: A61N 1/36157 Current A61N1/3616 takes precedence
• CPC Class Codes: A61N 1/3616 Voltage density or current density
• CPC Class Codes: A61N 1/36171 Frequency
• CPC Class Codes: A61N 1/36175 Pulse width or duty cycle
• CPC Class Codes: A61N 1/37235 Aspects of the external programmer

Abstract

The present specification discloses devices and methodologies for the treatment of transient lower esophageal sphincter relaxations (tLESRs). Individuals with tLESRs may be treated by implanting a stimulation device within the patient'"'"'s lower esophageal sphincter and applying electrical stimulation to the patient'"'"'s lower esophageal sphincter, in accordance with certain predefined protocols. The presently disclosed devices have a simplified design because they do not require sensing systems capable of sensing when a person is engaged in a wet swallow and have improved energy storage requirements.

Claims

1. A system for increasing pressure of a patient'"'"'s lower esophageal sphincter (LES), comprising:

at least one electrode configured to contact the LES;

a waveform generator coupled to the electrodes; and

a controller configured to electrically stimulate the LES to increase the pressure of the LES, and maintain an average pressure of the LES above a pressure level which reduces at least one of a frequency of occurrence or an intensity of transient lower esophageal sphincter relaxation (tLESR) symptoms in the patient both during and after stimulation by controlling the waveform generator to repeatedly;

a) generate and apply an electrical pulse train to the LES through the electrodes for a stimulation period, and b) terminate the electrical pulse train for a rest period, wherein at least one of an amplitude, frequency, or duration of said pulse train is defined such that pressure of the LES normalizes after at least five minutes from when stimulation is initiated.

2. The system of claim 1, wherein the maintained average pressure does not induce dysphagia in the patient and allows the patient to swallow a bolus during both the stimulation period and rest period.

3. The system of claim 1, wherein the controller is configured to determine parameters of the electrical pulse train that maintain the average pressure of the LES above the pressure level during the rest period.

4. The system of claim 1, wherein the controller is configured to control the waveform generator to stimulate the LES based on a predetermined trigger of at least one of time of day and supine of the patient.

5. The system of claim 1, wherein the controller is configured to adjust a length of the stimulation period and a length of the rest period to maintain the average pressure of the LES above the pressure level.

6. The system of claim 1, including a sensor coupled to the controller for sensing physiological data of the patient, the sensor sensing at least one of pH level at the LES and pressure of the LES, wherein the controller is configured to control the waveform generator based on the sensed physiological data.

7. The system of claim 1, wherein the controller and the waveform generator are enclosed in a common housing and implanted in the patient.

8. The system of claim 1, including an external programming device for configuring the controller to adjust at least one of the energy per stimulation period, duration of the stimulation period, frequency of the stimulation period, and a number of stimulation periods per day based on at least one of the frequency of occurrence or the intensity of tLESR symptoms in the patient.

9. The system of claim 1, including a disposable battery coupled to the waveform generator and the controller for powering the waveform generator and the controller.

10. The system of claim 1, wherein the controller is configured to control the waveform generator to set a pulse width of the electrical pulse train in a range from 1 μ

s to 1 second.

11. The system of claim 1, wherein the controller is configured to control the waveform generator to set a frequency of the electrical pulse train in a range from about 1 Hz to about 100 Hz.

12. The system of claim 1, wherein the controller is configured to control the waveform generator to set a current of pulses in the electrical pulse train in a range from 1 μ

Amp to 50 mAmps.

13. The system of claim 1, including a sensor coupled to the controller for sensing physiological data of a patient;

and a memory coupled to the controller for storing the sensed data of the patient, wherein the controller is configured to control the waveform generator to adjust parameters of the electrical pulse train applied to the LES based on an analysis of the stored data.

14. The system of claim 1, including at least one of an accelerometer and inclinometer coupled to the controller for sensing posture data of the patient, wherein the controller is configured to control the waveform generator to adjust parameters of the electrical pulse train applied to the LES based on an analysis of the posture data.

15. The system of claim 1, including an antenna coupled to the controller for wirelessly receiving instructions for instructing the controller to adjust parameters of the electrical pulse train applied to the LES, wherein the instructions are set by at least one of the patient and a trained professional.

16. The system of claim 1, wherein the controller is configured to perform a diagnostic test on the patient by controlling the waveform generator to adjust an amount of electrical energy stimulating the LES over a treatment period based on at least one of the frequency of occurrence or the intensity of tLESR symptoms in the patient.

17. A system for normalizing functionality of a patient'"'"'s lower esophageal sphincter (LES), comprising:

at least one electrode configured to contact the LES;

a waveform generator coupled to the electrodes; and

a controller configured to control the waveform generator to generate and apply an electrical pulse train to the LES through the electrodes during a stimulation period to produce said normalization of function in the LES during a rest period after termination of the electrical pulse train, which reduces at least one of a frequency of occurrence or an intensity of transient lower esophageal sphincter relaxation (tLESR) symptoms in the patient, wherein at least one of an amplitude, frequency, or duration of said pulse train is defined such that swallowing of the patient is not hindered by said stimulation.

18. The system of claim 17, wherein, prior to stimulation, the controller is configured with a length of the stimulation period and an electrical current of the pulse train that increases a pressure of the LES above a pressure level that reduces at least one of a frequency of occurrence or an intensity of acid reflux symptoms in the patient during the rest period.

19. The system of claim 17, wherein, prior to stimulation, the controller is configured to determine a length of the rest period that allows a pressure of the LES to increase above a pressure level that reduces at least one of a frequency of occurrence or an intensity of acid reflux symptoms in the patient and does not allow the pressure of the LES to decrease below the pressure level.

20. The system of claim 17, wherein the controller is configured with parameters of the electrical pulse train that produce a first increase in LES pressure during the stimulation period, and a second increase in LES pressure during the rest period.

21. The system of claim 17, wherein the controller is configured to determine parameters of the electrical pulse train that produce an increase in the LES pressure at a first rate during the stimulation period and at a second rate during the rest period.

22. A system for normalizing a function of a patient'"'"'s lower esophageal sphincter (LES), comprising:

at least one electrode configured to contact the LES;

a waveform generator coupled to the electrodes; and

a controller configured to control the waveform generator to generate and apply an electrical pulse train to the LES through the electrodes to normalize the function of the LES, which reduces at least one of a frequency of occurrence or an intensity of tLESR symptoms in the patient while allowing the patient to swallow during electrical stimulation wherein at least one of an amplitude, frequency, or duration of said pulse train is defined such that said function of the LES normalizes after at least five minutes from when stimulation is initiated.

23. The system of claim 22, wherein the bolus has a volume of greater than 1 cubic centimeter (cc).

24. The system of claim 22, wherein the controller is configured to control the waveform generator so that an increased pressure level of the LES is below a pressure level that prevents the patient from swallowing a bolus.

25. The system of claim 22, wherein the controller is configured to control the waveform generator so that an increased pressure level of the LES is below a pressure level that restricts the opening capacity of patient'"'"'s LES when swallowing a bolus.

26. The system of claim 22, wherein the controller is configured to control the waveform generator so that the electrical stimulation does not inhibit a patient'"'"'s esophageal motility.

27. A system for increasing pressure of a patient lower esophageal sphincter (LES), comprising:

at least one electrode configured to contact the LES;

a waveform generator coupled to the electrodes;

a battery powering the waveform generator; and

a controller configured to control the waveform generator to generate and apply an electrical pulse train to the LES through the electrodes to increase the pressure of the LES, the electrical pulse train being controlled by the controller so that an amount of electrical energy consumed from the battery when stimulating the LES is an energy amount that maintains an average pressure of the LES above a pressure level which reduces at least one of a frequency of occurrence or an intensity of tLESR symptoms in the patient while maintaining at least a minimum charge on the battery to electrically power the waveform generator for a predetermined time period, wherein the controller is configured to control the waveform generator so that the increased pressure level of the LES is below a pressure level that prevents the patient from swallowing a bolus.

28. The system of claim 27, wherein the controller is configured to determine a stimulation time for stimulating the LES to reduce at least one of the frequency of occurrence or the intensity of tLESR symptoms in the patient, and electrically power the waveform generator for the predetermined time period.

29. The system of claim 27, wherein the controller is configured to determine at least one of a pulse width, electrical current, frequency and energy of the electrical pulse train to reduce at least one of the frequency of occurrence or the intensity of tLESR symptoms in the patient, and electrically power the waveform generator for the predetermined time period.

30. The system of claim 27, wherein the controller is configured to consume between 30 nano-amp hours and 3 micro-amp-hours of energy during a stimulation period to reduce the tLESR symptoms in the patient for at least one hour, and does not consume more than 3 micro-amp hours of energy per stimulation period.

31. The system of claim 27, wherein the controller is configured to cumulatively consume between 300 nano-amp hours and 30 micro-amp-hours of energy over a plurality of stimulation periods to reduce the tLESR symptoms in the patient for at least 24 hours, and does not consume more than 30 micro-amp hours of energy per day.

32. A method of treating a patient with transient lower esophageal sphincter relaxation (tLESR) symptoms, wherein said patient has a lower esophageal sphincter (LES) and wherein said LES has a pressure, the method comprising:

maintaining an average pressure of the LES above a pressure level which reduces at least one of a frequency of occurrence or an intensity of the tLESR symptoms both during and after stimulation by applying an electrical pulse train to the LES through electrodes for a stimulation period to increase the pressure of the LES above the pressure level, and terminating the electrical pulse train for a rest period wherein at least one of an amplitude, frequency, or duration of said pulse train is defined such that the increased pressure of the LES is below a pressure level that prevents the patient from swallowing a bolus.

33. The method of claim 32, wherein the LES is repeatedly stimulated to maintain the average pressure of the LES in a pressure range which is above a first pressure level to at least one of the frequency of occurrence or the intensity of the tLESR symptoms in the patient and below a second pressure level to allow the patient to swallow during both the stimulation period and rest period.

34. The method of claim 33, wherein a controller determines parameters of the electrical pulse train that maintain the average pressure of the LES above the pressure level during the rest period.

35. The method of claim 34, wherein the controller controls a waveform generator to stimulate the LES when the pressure of the LES decreases to a third pressure level during the rest period.

36. The method of claim 34, wherein the controller adjusts a length of the stimulation period and a length of the rest period to maintain the average pressure of the LES above the pressure level.

37. The method of claim 34, wherein the controller is configured to control the waveform generator to set a pulse width of the electrical pulse train in a range from about 1 μ

s to about 1 second.

38. The method of claim 34, wherein the controller is configured to control the waveform generator to set a frequency of the electrical pulse train in a range from about 1 Hz to about 100 Hz.

39. The method of claim 34, wherein the controller is configured to control the waveform generator to set a current of pulses in the electrical pulse train in a range from about 1 uAmp to about 50 mAmps.

40. The method of claim 34, wherein the controller is configured to perform a diagnostic test on the patient by controlling the waveform generator to vary parameters of the electrical pulse train to determine a pressure response of the LES based on different electrical stimulation.

41. The method of claim 32, wherein:

achieving said pressure level occurs after a minimum period selected from the group consisting of at least 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 12 hours, 24 hours, or any time increment therein.

42. The method of claim 32, wherein:

said electrical stimulation is initiated prior to a predetermined time;

said predetermined time is associated with an tLESR triggering event; and

said initiation occurs prior to said predetermined time by a minimum period selected from the group consisting of at least 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 12 hours, 24 hours, or any time increment therein.

43. The method of claim 32, further comprising:

programming said stimulation device, wherein said programming is dependent upon a plurality of stimulation parameters that determine the application of electrical stimulation to the patient LES, and wherein said stimulation parameters are selected, at least in part, to treat tLESR without inhibiting patient swallowing.

44. The method of claim 32, wherein electrical stimulation is applied to the patient LES while the patient swallows, during periods of esophageal motility, or during esophageal peristalsis.

45. The method of claim 32, wherein electrical stimulation is applied to the patient LES in accordance with a preset period and wherein said preset period is not dependent upon a physiological state of a patient.

46. The method of claim 32, wherein electrical stimulation is applied to the patient LES in accordance with a preset period and wherein said preset period is not dependent upon the patient swallowing, esophageal motility, esophageal peristalsis, or being in a feeding state.

47. The method of claim 32, wherein electrical stimulation is applied to the patient LES that is not dependent upon a physiological state of the patient.

48. The method of claim 32, wherein electrical stimulation is applied to the patient LES that is not dependent upon a sensed physiological state of the patient.

49. The method of claim 32, wherein electrical stimulation is applied to the patient LES that is not dependent upon the patient swallowing, esophageal motility, esophageal peristalsis, or being in a feeding state.

50. The method of claim 32, wherein sufficient electrical stimulation is applied to the patient LES to increase said pressure but not to inhibit patient swallowing, esophageal motility, or esophageal peristalsis.

51. The method of claim 32, wherein electrical stimulation is applied to the patient LES causing an increase in said pressure of at least 5% only after an elapsed period of time of at least one minute.

52. The method of claim 32, wherein said electrical stimulation normalizes lower esophageal function, normalizes LES pressure, or increases LES pressure to a normal physiological range only after an elapsed period of time of at least one minute.

53. The method of claim 32, wherein said stimulation causes a non-instantaneous or delayed increase in said pressure.

54. The method of claim 32, wherein said electrical stimulation causes a delayed increase in said pressure and wherein said delayed increase in the pressure normalizes LES function, normalizes LES pressure, increases LES pressure to a normal physiological range, or increases LES pressure by at least 3%.

55. The method of claim 32, wherein said electrical stimulation causes an increase in said pressure after said electrical stimulation is terminated.

56. The method of claim 32, wherein said electrical stimulation has a first level, wherein said stimulation causes an increase in said pressure after said electrical stimulation is decreased from said first level.

57. The method of claim 32, wherein said electrical stimulation is applied in accordance with at least one on period, wherein said on period is between 1 second and 24 hours and is not triggered by, substantially concurrent to, or substantially simultaneous with an incidence of tLESR, and at least one off period, wherein said off period is greater than 10 seconds.

58. The method of claim 32, wherein said electrical stimulation is applied having a current from a single electrode pair ranging from about 1 mAmp to about 8 mAmp.

59. The method of claim 32, wherein said electrical stimulation has a pulse duration within a range of 5 μ

sec to 1 second.

60. The method of claim 32, wherein said electrical stimulation has a pulse duration of approximately 1 msec.

61. The method of claim 32, wherein said electrical stimulation has a pulse duration of approximately 200 μ

sec.

62. The method of claim 32, wherein the device incorporates an accelerometer or inclinometer to measure patient positional activity;

and applying electrical stimulation based upon one or more of the following parameters as measured by said accelerometer or inclinometer;

time spent in the supine position or level of inclination.

63. A macrostimulator programmed, adapted to, or configured to perform the method of claim 32.

64. A macrostimulator comprising at least one electrode, an energy source, and a pulse generator in electrical communication with the at least one electrode and energy source, wherein said pulse generator is programmed, adapted to, or configured to perform the method of claim 32.

65. A macrostimulator implanted in a patient configured to perform the method of claim 32.

66. A macrostimulator implanted in a patient comprising at least one electrode, an energy source, and a pulse generator in electrical communication with the at least one electrode and energy source, wherein said pulse generator is programmed, adapted to, or configured to perform the method of claim 32.

67. A macrostimulator programmed, adapted to, or configured to perform the method of claim 32 wherein electrical stimulation is initiated, terminated or otherwise modified based upon sensed data.

68. A macrostimulator comprising at least one electrode, an energy source, and a pulse generator in electrical communication with the at least one electrode and energy source, wherein said pulse generator is programmed, adapted to, or configured to perform the method of claim 32 wherein electrical stimulation is initiated, terminated or otherwise modified based upon sensed data.

69. A macrostimulator implanted in a patient configured to perform the method of claim 32 wherein electrical stimulation is initiated, terminated or modified based upon sensed data.

70. A macrostimulator implanted in a patient comprising at least one electrode, an energy source, and a pulse generator in electrical communication with the at least one electrode and energy source, wherein said pulse generator is programmed, adapted to, or configured to perform the method of claim 32 wherein electrical stimulation is initiated, terminated, or otherwise modified based upon sensed data.

71. A macrostimulator programmed, adapted to, or configured to perform the method of claim 32 wherein electrical stimulation is initiated or terminated based upon sensed data and wherein the sensed data is at least one of LES pressure, esophageal pH, inclinometer data, temperature, or accelerometer data.

72. A macrostimulator comprising at least one electrode, an energy source, and a pulse generator in electrical communication with the at least one electrode and energy source, wherein said pulse generator is programmed, adapted to, or configured to perform the method of claim 32 wherein electrical stimulation is initiated or terminated based upon sensed data and wherein the sensed data is at least one of LES pressure, esophageal pH, inclinometer data, temperature, or accelerometer data.

73. A macrostimulator implanted in a patient configured to perform the method of claim 32 wherein electrical stimulation is initiated or terminated based upon sensed data and wherein the sensed data is at least one of LES pressure, esophageal pH, inclinometer data, temperature, or accelerometer data.

74. A macrostimulator implanted in a patient comprising at least one electrode, an energy source, and a pulse generator in electrical communication with the at least one electrode and energy source, wherein said pulse generator is programmed, adapted to, or configured to perform the method of claim 32 wherein electrical stimulation is initiated or terminated based upon sensed data and wherein the sensed data is at least one of LES pressure, esophageal pH, inclinometer data, temperature, or accelerometer data.

75. A method of treating a patient with transient lower esophageal sphincter relaxation (tLESR) symptoms, the method comprising:

(a) implanting a stimulation device in the patient to contact the patient LES, (b) applying electrical stimulation to the patient LES, and (b) maintaining an average pressure of the LES above a pressure level both during and after electrical stimulation for a stimulation period to increase the pressure of the LES above the pressure level, and terminating the electrical stimulation for a rest period wherein at least one of an amplitude, frequency, or duration of said electrical stimulation is defined such that the increased pressure of the LES is below a pressure level that prevents the patient from swallowing a bolus.

76. The method of claim 75, wherein:

achieving said pressure level occurs after a minimum period selected from the group consisting of at least 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 12 hours, 24 hours, or any time increment therein.

77. The method of claim 75, wherein:

said electrical stimulation is initiated prior to a predetermined time;

said predetermined time is associated with a tLESR triggering event; and

said initiation occurs prior to said predetermined time by a minimum period selected from the group consisting of at least 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 12 hours, 24 hours, or any time increment therein.

78. The method of claim 75, further comprising:

programming said stimulation device, wherein said programming is dependent upon a plurality of stimulation parameters that determine the application of electrical stimulation to the patient LES, and wherein said stimulation parameters are selected, at least in part, to treat tLESR symptoms without inhibiting patient swallowing.

79. The method of claim 75, wherein electrical stimulation is applied to the patient LES while the patient swallows, during periods of esophageal motility, or during esophageal peristalsis.

80. The method of claim 75, wherein electrical stimulation is applied to the patient LES in accordance with a preset period and wherein said preset period is not dependent upon a physiological state of a patient.

81. The method of claim 75, wherein electrical stimulation is applied to the patient LES in accordance with a preset period and wherein said preset period is not dependent upon the patient swallowing, esophageal motility, esophageal peristalsis, or being in a feeding state.

82. The method of claim 75, wherein electrical stimulation is applied to the patient LES that is not dependent upon a physiological state of the patient.

83. The method of claim 75, wherein electrical stimulation is applied to the patient LES that is not dependent upon a sensed physiological state of the patient.

84. The method of claim 75, wherein electrical stimulation is applied to the patient LES that is not dependent upon the patient swallowing, esophageal motility, esophageal peristalsis, or being in a feeding state.

85. The method of claim 75, wherein sufficient electrical stimulation is applied to the patient LES to increase said pressure but not to inhibit patient swallowing, esophageal motility, or esophageal peristalsis.

86. The method of claim 75, wherein electrical stimulation is applied to the patient LES causing an increase in said pressure of at least 5% only after an elapsed period of time of at least one minute.

87. The method of claim 75, wherein said electrical stimulation normalizes lower esophageal function, normalizes LES pressure, or increases LES pressure to a normal physiological range only after an elapsed period of time of at least one minute.

88. The method of claim 75, wherein said stimulation causes a non-instantaneous or delayed increase in said pressure.

89. The method of claim 75, wherein said electrical stimulation causes a delayed increase in said pressure and wherein said delayed increase in the pressure normalizes LES function, normalizes LES pressure, increases LES pressure to a normal physiological range, or increases LES pressure by at least 3%.

90. The method of claim 75, wherein said electrical stimulation causes an increase in said pressure after said electrical stimulation is terminated.

91. The method of claim 75, wherein said electrical stimulation has a first level, wherein said stimulation causes an increase in said pressure after said electrical stimulation is decreased from said first level.

92. The method of claim 75, wherein said electrical stimulation is applied in accordance with at least one on period, wherein said on period is between 1 second and 24 hours and is not triggered by, substantially concurrent to, or substantially simultaneous with an incidence of tLESR, and at least one off period, wherein said off period is greater than 10 seconds.

93. The method of claim 75, wherein said electrical stimulation is applied having a current from a single electrode pair ranging from about 1 mAmp to about 8 mAmp.

94. The method of claim 75, wherein said electrical stimulation has a pulse duration within a range of 5 μ

sec to 1 second.

95. The method of claim 75, wherein said electrical stimulation has a pulse duration of approximately 1 msec.

96. The method of claim 75, wherein said electrical stimulation has a pulse duration of approximately 200 μ

sec.

97. The method of claim 75, wherein the device incorporates an accelerometer or inclinometer to measure patient positional activity;

and applying electrical stimulation based upon one or more of the following parameters as measured by said accelerometer or inclinometer;

time spent in the supine position or level of inclination.

98. A method of treating a patient with transient lower esophageal sphincter relaxation (tLESR) symptoms, the method comprising:

(a) implanting the stimulation device in the patient to contact the patient LES;

(b) applying electrical stimulation to the patient LES;

(b) measuring one or more parameters selected from the group consisting of patient feed state including type of feed;

patient position;

patient activity;

patient reflux profile;

LES pressure;

LES electrical activity;

LES mechanical activity gastric pressure;

gastric electrical activity;

gastric chemical activity;

gastric temperature;

gastric mechanical activity;

patient intuition;

vagal neural activity; and

, splanchnic neural activity;

(c) inputting the collected data into an algorithm; and

(d) applying electrical stimulation based upon a summary score calculated by said algorithm to maintain an average pressure of the LES above a pressure level both during and after electrical stimulation for a stimulation period to increase the pressure of the LES above the pressure level, and terminating the electrical stimulation for a rest period wherein at least one of an amplitude, frequency, or duration of said electrical stimulation is defined such that the average pressure of the LES is below a pressure level that prevents the patient from swallowing a bolus.