SYSTEMS AND METHODS FOR ENHANCEMENT

OF AND CONTINUOUS BIASING OF AFFERENT

NERVES FOR TREATMENT OF OBESITY

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 60/859,751, filed November 17, 2006, and entitled "System and Method of Continuous Biasing of Afferent Nerves for Treatment of Obesity," and further claims the benefit of U.S. Provisional Application No. 60/859,609, filed November 17, 2007, and entitled "System and Method for Enhancement of Afferent Nerves for Treatment of Obesity."

REFERENCE REGARDING FEDERALLY SPONSORED RESEARCH OR

DEVELOPMENT [0002] Not applicable

SEQUENTIAL LISTING [0003] Not applicable

BACKGROUND OF THE INVENTION

1. Field of the Disclosure

[0004] The present invention relates generally to the use of subthreshold afferent nerve enhancement or continuous biasing of afferent nerves for the treatment of obesity. More specifically, subthreshold electrical, electromechanical, noise signals are generated by a stimulator positioned on an external wall of a physiological structure of the gastrointestinal (GI) tract as a continuous bias signal, or after the detection of a change in physiological structure. The subthreshold signals act to amplify the generator potential of proprioreceptive nerve endings connected to the GI tract, thereby causing a faster and more frequent response to the natural stimuli originating from food intake.

2. Description of the Background of the Disclosure

[0005] Bariatric surgical treatments are increasingly being used to treat obesity. One of the most common bariatic surgical treatments is adjustable laparoscopic banding. Laparoscopic bandings, or LAP -BANDS™, are surgical bands used to constrict the opening and expansion of the superior stomach to reduce food intake in obese patients. The bands are positioned either laproscopically or via open surgery. Many LAP-BANDS™ have a means to transcutaneously adjust the constriction via an injection port, with an adjoining tube to the implant, strategically located just below the surface of the skin. Saline is injected or removed by a physician to adjust the band diameter. The LAP-BAND™ serves dual functions: first, to prevent large food sections from entering the stomach, and second, to reduce the perceived stomach volume inducing a faster perception of being full by the patient. Complications that arise .from the use of LAP-BANDS™ include pain, vomiting, esophageal distension, band erosion, band slippage and migration, as well as reduced weight loss due to non-compliance with post-operative dietary and exercise guidelines.

[0006] More recently, methods for the treatment of obesity have been employed where an electrostimulation or pacemaker implant device regulates gastric motility and efficiency of the gastrointestinal tract. These methods of treatment involve laparoscopically attaching the electrostimulation device to the gastrointestinal tract and applying continuous or sequential electrical pulses to the GI tract in order to regulate conditions such as contraction propagation and diameter. The suprathreshold electrical stimulation accelerates or attenuates the transit of material through the GI tract. Computer feedback control is also utilized to regulate, fluctuate, and adjust the stimulation parameters based on sensed motor activity of the gastrointestinal tract.

[0007] Other methods for the treatment of obesity involve electrical stimulation of the vagus or pneumogastric nerve, which controls food motility through the stomach. These stimulation methods involve the application of modulating electrical signals to the vagus nerve using a neurostimulating device positioned inside or outside the body. The electrical stimulation is applied directly or in proximity to the vagus nerve. The application of a predetermined level of electrical stimulation to the vagus nerve affects gastric motility, stomach contraction and distension, and specific brain regions involved in appetite suppression.

[0008] The upper GI system undergoes phases of physiologic changes during food consumption. Throughout this process information is exchanged between the gut and the brain through the parasympathetic vagal afferent pathway, as well as the sympathetic sensory (primarily splanchnic) afferent pathway. Physiologic reflexes conducted via the vagal afferent nerves are initiated by the onset of food volume in the stomach, by activating the mechanosensitive receptors in the stomach wall. As food volume is increased, the stomach is distended further, with more vagal afferent neurons begin recruited in signaling to the brain. At some point the distension exceeds the threshold of pain receptors in the stomach, sending pain related afferent signals through the spinal nerve projection.

[0009] Recently, the stochastic resonance phenomenon has been utilized to improve the function of threshold-based sensory cells. These' methods involve the addition of an externally produced signal to the input signal of a sensory cell, or to the sensory cell itself, so that the input signal is converted from a subthreshold input to a suprathreshold input. In these methods, a sensory cell area is located and a bias signal is applied to the sensory cell area. The application of the bias signal causes the threshold of sensory cells to be exceeded in response to a subthreshold input stimulus, thereby effectively lowering the threshold of the sensory cells within the sensory cell area.

SUMMARY OF THE INVENTION

[0010] According to one aspect of the present invention, a method for applying an artificial subthreshold signal to a patient's gastrointestinal tract for the treatment of obesity comprises the step of detecting a change in a physiological structure of the gastrointestinal tract. The method further includes the step of applying the subthreshold signal to an external wall of the physiological structure of the gastrointestinal tract based on the change in physiological structure in order to increase the reception of afferent nerves associated therewith. Still further, the method includes the step of terminating the subthreshold signal in response to subsequent physiological events of the gastrointestinal tract.

[0011] According to another aspect of the present invention, a system for subthreshold afferent nerve enhancement of a patient's gastrointestinal tract for the treatment of obesity includes a band positioned adjacent to an external wall of the physiological structure of the gastrointestinal tract. The system further includes a sensor associated with the external wall

-A-

of the physiological structure of the gastrointestinal tract and a subthreshold signal generator in communication with the band.

[0012] According to still another aspect of the present invention, an obesity treatment method includes the steps of generating a bias signal at a level insufficient to create a response in a target tissue within the gastrointestinal tract and applying the bias signal continuously to the target tissue within the gastrointestinal tract.

[0013] According to yet another aspect of the present invention, a system for afferent nerve enhancement of a patient's gastrointestinal tract for the treatment of obesity includes a band positioned adjacent to an external wall of the physiological structure of the gastrointestinal tract. The system further includes a bias signal generator in communication with the band, wherein the bias signal generator generates a continuous bias signal at a level insufficient to create a response in a target tissue within the gastrointestinal tract.

[0014] According to a further aspect of the present invention, a system for afferent nerve enhancement of a patient's gastrointestinal tract for the treatment of obesity includes an array of electrodes positioned adjacent to an external wall of the physiological structure of the gastrointestinal tract. The system further includes a bias signal generator in communication with the array of electrodes, wherein the bias signal generator generates a continuous bias signal at a level insufficient to create a response in a target tissue within the gastrointestinal tract.

[0015] Other aspects and advantages of the present invention will become apparent upon consideration of the following detailed description, wherein like structures are given like reference numerals.

BRIEF DESCRIPTION OF THE DRAWINGS

[0016] FIG. 1 is a cross-sectional illustration of a segment of the gastrointestinal tract near the stomach.

[0017] FIG. 2 illustrates a device suitable for use on the gastrointestinal tract.

[0018] FIG. 3 is a representation of a band of a further embodiment positioned on the external wall of the stomach around the upper section of the stomach at the fundus.

[0019] FIG. 4 is a representation of a band capable of providing subthreshold mechanical signals positioned on the external wall of the stomach around the upper section of the stomach at the fundus.

[0020] FIG. 5A is a side view of a band suitable for use in one embodiment. FIG. 5B depicts the surface of the band that is positioned on the external wall of the stomach. FIG. 5C depicts the surface of the band not in contact with the external wall of the stomach.

[0021] FIG. 6 is a representation of a band of another embodiment in place on the external wall of the stomach around the upper section of the stomach at the fundus providing increased restriction to the stomach as a result of increased food intake.

[0022] FIG. 7 illustrates an embodiment of a device suitable for use in the continuous biasing of the gastrointestinal tract.

[0023] FIG. 8 is a representation of a band of one embodiment positioned on the external wall of the stomach around the upper section of the stomach at the fundus.

[0024] FIG. 9 is a representation of a band capable of providing continuous mechanical bias positioned on the external wall of the stomach around the upper section of the stomach.

[0025] FIG. 10 illustrates an embodiment of a device where an array of electrodes is positioned on the external wall of the stomach.

[0026] FIG. 11 is a graphical representation of a patient's enhanced response to external stimuli resulting from the application of subthreshold stimulation to the gastrointestinal tract.

[0027] FIG. 12 is another graphical depiction of a patient's enhanced response to external stimuli resulting from the application of subthreshold stimulation to the gastrointestinal tract.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0028] The present invention is directed to a system and method for subthreshold afferent nerve enhancement of a patient's gastrointestinal tract for the treatment of obesity and a system and method of continuous biasing of afferent nerves for treatment of obesity.

[0029] FIG. 1 is a cross-sectional representation of a segment of the gastrointestinal tract near the stomach 20. The stomach 20 is an expanded section of the gastrointestinal tract located between the esophagus 22 and the duodenum 24. The anatomical term for the

junction orifice between the stomach 20 and the esophagus 22 is the cardia or cardiac sphincter 26. The central region of the stomach is referred to as the body or corpus 28 and the upper curvature of the stomach is called the fundus 30. The right side of the stomach 20 is referred to as the greater curvature 32, and the left side of the stomach is called the lesser curvature 34. Pylorus or pyloric sphincter 36 is the anatomical term for the most distal section of the stomach 20.

[0030] FIG. 2 shows the components of a system 50 suitable for use in one embodiment of the present disclosure. As seen in FIG. 2, the system 50 includes a band 52 containing stimulating electrodes 54 and a detector 56 capable of sensing changes in a physiological structure of the gastrointestinal tract near the stomach 20, such as mechanical contractions or distensions of the stomach 20. The band 52 is connected to a subthreshold noise generating device 58 via an electrical lead 60. The subthreshold noise generating device 58 commences generating an artificial subthreshold signal when the detector 56 senses a specific change in a physiological structure of the gastrointestinal tract. The application of random broadband subthreshold noise via the stimulating electrodes 54 accompanied by a patient's natural subthreshold response to external stimuli leads to fast and frequent firing of stretch receptors in the stomach 20, which results in a more readily achieved feeling of satiety for a patient before the onset of pain sensation. In another embodiment, a mechanical vibrating material, such as piezoelectric material, is used as a subthreshold signal generator.

[0031] FIG. 3 is an illustration of a band 52 of one embodiment of the present disclosure positioned on the external wall of the stomach 20 around the upper section of the stomach 20 at the fundus 30. Surgical placement of the band 52 is performed by laparoscopically guiding one end portion 62 of the band 52 around the upper circumference of the stomach 20 and securing the end portion 62 to a remaining end portion 64 of the band 52 with sutures 68. In another embodiment, closure of the band 52 during laparoscopic placement is achieved using a buckle clasp or other locking element. Optionally during surgical installation, portions of the band 52 can be affixed to an external wall 69 of the stomach 20 to prevent band slippage. Fixation of the band 52 on the external wall 69 of the stomach 20 is achieved through the use of mussel adhesive proteins or other biocompatible adhesives. In another embodiment, the band 52 can be mechanically affixed to the external wall 69 of the stomach 20 using sutures or other devices.

[0032] Additionally, FIG. 3 illustrates components of a system 70 suitable for use in a further embodiment. As depicted in FIG. 3, the band 52 can be positioned on the external wall 69 of the stomach 20 around the upper section of the stomach 20 at the fundus 30. The band 52 contains a detector 74 capable of sensing changes in a physiological structure of the gastrointestinal tract near the stomach 20. The band 52 is connected to a subthreshold noise generating device 78 via an electrical lead 80. The subthreshold noise generating device 78 commences generating an artificial subthreshold signal when the detector 74 senses a specific change in the physiological structure of the gastrointestinal tract. Stimulating electrodes 76 are positioned on the external wall 69 of the lower stomach 20 remote from the detector 74. The stimulating electrodes 76 are connected to the noise generating device 78 via electrical leads 82. The application of random broadband subthreshold noise to the stomach 20 via the stimulating electrodes 78 accompanied by a patient's natural subthreshold response to external stimuli leads to fast and frequent firing of stretch receptors in the stomach 20, which results in a feeling of satiety for a patient before the onset of pain sensation.

[0033] FIG. 4 is a representation of a further embodiment of a band 90 capable of providing subthreshold mechanical signals positioned on the external wall 69 of the stomach 20 around the upper section of the stomach 20 at the fundus 30. As depicted in FIG. 4, the band 90 can be positioned on the external wall 69 of the stomach 20 around the upper section of the stomach 20 at the fundus 30. The band 90 contains a detector 92 capable of sensing changes in a physiological structure of the gastrointestinal tract near the stomach 20. The band 90 is connected to a mechanical vibrator 94. The mechanical device 94 commences vibration when the detector 92 senses a specific change in the physiological structure of the gastrointestinal tract. The application of the subthreshold vibration to the stomach 20 accompanied by a patient's natural subthreshold response to external stimuli leads to fast and frequent firing of stretch receptors in the stomach 20, which results in a feeling of satiety for a patient before the onset of pain sensation. In another embodiment, the subthreshold signal can be electromechanical in nature.

[0034] FIGS. 5A-C are illustrations of a closed band 100 suitable for use in a further embodiment. FIG. 5A is a side view illustration of the closed band 100. FIG. 5B and FIG. 5C are plan views of each side of the band 100 prior to surgical closure. The band 100 contains stimulating electrodes 104 and a detector 106 capable of sensing changes in a

physiological structure of the gastrointestinal tract near the stomach 20. FIG. 5B depicts an inner surface 107a of the band 100 that engages the external wall 69 of the stomach 20. The stimulating electrodes 104 are positioned adjacent to the external wall 69 of the stomach 20. FIG. 5C depicts an outer surface 107b of the band 100 not in contact with the external wall of the stomach 20. The outer and inner surfaces 107a, 107b of the band 100 may be composed of the same material, or of different materials.

[0035] In the embodiment of FIGS. 5A-5C, the band 100 is comprised of biocompatible, hermetically sealed material and is available in varying stiffness and lengths. Suitable materials for the band 100 include conducting polymeric materials, dielectric elastomers, and elastic composite materials containing conductive particles or fibers. These materials are highly compliant with stretch and conform to the dimension of the stomach as it stretches. As illustrated in FIGS. 5A-5C, power for the noise generator is provided by a power generator 102 positioned adjacent to the band 100. Power is generated through the conversion of mechanical movements of the stomach 20 into electrical power, thus eliminating the need for batteries or other means of power. In another embodiment, the power source resides with a stimulation generator positioned remotely from the band 100. In yet another embodiment, all processing electronics reside in the generator 102 so that only a stretch sensor 106, stimulating electrodes 104, and electrical leads 82 (FIG. 3) are near or on the stomach 20.

[0036] FIG. 6 is a representation of a band 110 of another embodiment in place around the external wall 69 of the upper section of the stomach 20 at the fundus 30. The band 110 depicted in FIG. 6 provides increased restriction to the stomach 20 with increased food intake. A stretch sensor 112 disposed on the band 110 has a resistance that is proportional to its elongation. A change in resistance is used to switch on a stimulation generator circuit 114 thereby initiating electrical stimulation. Alternatively, the stretch sensor 112 may behave like a transducer that converts mechanical stretch to electrical charge that is then used to switch on the generator circuit 114. The stimulation generator circuit 114 generates a subthreshold signal only when stretched beyond a set point, due to distention of the stomach 20 as a result of food intake. Once food intake ceases, the band 110 relaxes, and the subthreshold noise generation is terminated. Periodic termination of the subthreshold noise eliminates potential for unwanted stimuli, such as perceived hunger.

[0037] FIG. 7 illustrates components of a system 150 suitable for use in one embodiment of the present disclosure. As seen in FIG. 7, the system 150 includes a band 152 containing stimulating electrodes 154. The band 152 is connected to a bias generating device 158 via an electrical lead 160. The bias generating device 158 supplies a continuous bias signal at a level insufficient to create an afferent nerve response. The continuous application of bias via the stimulating electrodes 154 accompanied by a patient's natural subthreshold response to external stimuli leads to fast and frequent firing of stretch receptors in the stomach 20, which results in a more readily achieved feeling of satiety for a patient before the onset of pain sensation. In another embodiment, a mechanical vibrating material, such as piezoelectric material, is used as the bias signal generator.

[0038] FIG. 8 is an illustration of a further embodiment where a band 152 is positioned on the external wall 69 of the stomach 20 around the upper section of the stomach 20 at the fundus 30. Surgical placement of the band 152 is performed by laparoscopically guiding one end portion 62 of the band 152 around an upper circumference of the stomach 20 and securing the end portion 162 to a remaining end portion 164 of the band 152 with sutures 68. In another embodiment, closure of the band 152 during laparoscopic placement is achieved using a buckle clasp or other locking element. Optionally during surgical installation, portions of the band 152 can be fixed to the external wall 69 of the stomach 20 to prevent band slippage. Fixation of the band 152 on the external wall 69 of the stomach 20 is achieved through the use of mussel adhesive proteins or other biocompatible adhesives. In another embodiment, the band 152 can be mechanically affixed to the external wall of the stomach 20 using sutures or other devices.

[0039] Additionally, FIG. 8 illustrates components of a system 170. As depicted in FIG. 8, the band 152 can be positioned on the external wall 69 of the stomach 20 around the upper section of the stomach 20 at the fundus 30. In this embodiment, the band 152 is connected to a bias generating device 178 via an electrical lead 180. The bias generating device 178 supplies a continuous bias signal at a level insufficient to create an afferent nerve response. The application of continuous bias signals to the stomach 20 via stimulating electrodes 176 located within the band 152 or remote from the band 152 accompanied by a patient's natural subthreshold response to external stimuli leads to fast and frequent firing of stretch receptors

in the stomach 20, which results in a feeling of satiety for a patient before the onset of pain sensation.

[0040] FIG. 9 illustrates an embodiment of the present disclosure where a band 190 capable of providing continuous mechanical bias signals is positioned on the external wall 69 of the stomach 20 around the upper section of the stomach 20 at the fundus 30. The band 190 is connected to a mechanical vibrator 194. The mechanical device 194 supplies a continuous bias signal at a level insufficient to create an afferent nerve response. The application of the bias to the stomach 20 accompanied by a patient's natural subthreshold response to external stimuli leads to fast and frequent firing of stretch receptors in the stomach 20, which results in a feeling of satiety for a patient before the onset of pain sensation. In another embodiment of the present disclosure, the bias signal can be electromechanical in nature.

[0041] In the embodiment of the present disclosure depicted in FIG. 9, the band 190 is comprised of biocompatible, hermetically sealed material and is available in varying stiffness and lengths. Suitable materials for the band 190 include conducting polymeric materials, dielectric elastomers, and elastic composite materials containing conductive particles or fibers. Power for the bias generator can be provided by a power generator 196 positioned adjacent to the band 190. Power is generated through the conversion of mechanical movements of the stomach 20 into electrical power, thus eliminating the need for batteries or other means of power. In another embodiment, the power source resides with a bias signal generator positioned remotely from the band 190. In yet another embodiment, all processing electronics reside in the generator 196 so that only the stimulating electrodes and electrical leads are near or on the stomach 20.

[0042] FIG. 10 illustrates an embodiment of a device suitable for use where an array of electrodes is positioned on the external wall 69 of the stomach 20. In this embodiment, a bias generating device 200 supplies a continuous bias signal at a level insufficient to create an afferent nerve response. Stimulating electrodes 202 are connected to the bias generating device 200 via electrical leads 204. The application of continuous bias to the stomach 20 via the stimulating electrodes 202 accompanied by a patient's natural subthreshold response to external stimuli leads to fast and frequent firing of stretch receptors in the stomach 20, which results in a feeling of satiety for a patient before the onset of pain sensation.

[0043] FIG. 11 is a graphical representation of a patient's enhanced response to external stimuli resulting from the application of subthreshold stimulation to the gastrointestinal tract. As shown in the embodiment depicted in FIG. 11, the subthreshold noise generating device 58 of FIG. 2 commences generating an artificial subthreshold signal when the detector 56 senses a specific change in distension of the band 52. The application of random broadband subthreshold noise via the stimulating electrodes 54 accompanied by a patient's natural subthreshold response to external stimuli results in a more readily achieved feeling of satiety 250 before the onset of pain sensation. Conversely, when the subthreshold signal is not applied, the patient's natural subthreshold response to external stimuli does not achieve satiety until the stomach or band is stretched to a larger extent 252.

[0044] FIG. 12 is a graphical depiction of a patient's enhanced response to external stimuli resulting from the application of subthreshold stimulation to the gastrointestinal tract. In this embodiment, the combination 270 of random broadband subthreshold noise 271 via the stimulating electrodes 54 accompanied by a patient's natural subthreshold response to external stimuli 272 results in surpassing the threshold of satiety 274. Action potential spikes in the chart 276 depict when the threshold of satiety 274 is surpassed.

[0045] Although the present disclosure has been described relative to specific exemplary embodiments thereof, it will be understood by those skilled in the art that modifications can be made thereto without departing from the scope and spirit of the disclosure.

INDUSTRIAL APPLICATION

An advantageous application for the disclosure lies in subthreshold afferent nerve enhancement for combating obesity.