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EP1296743A1 - Traitement de l'obesite par stimulation bilaterale du nerf vague - Google Patents

Traitement de l'obesite par stimulation bilaterale du nerf vague

Info

Publication number
EP1296743A1
EP1296743A1 EP00955908A EP00955908A EP1296743A1 EP 1296743 A1 EP1296743 A1 EP 1296743A1 EP 00955908 A EP00955908 A EP 00955908A EP 00955908 A EP00955908 A EP 00955908A EP 1296743 A1 EP1296743 A1 EP 1296743A1
Authority
EP
European Patent Office
Prior art keywords
stimulating
vagi
electrical signal
patient
pulses
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP00955908A
Other languages
German (de)
English (en)
Inventor
Burke Barrett
Ramish K. Reddy
Mitchell Roslin
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Livanova USA Inc
Original Assignee
Cyberonics Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Cyberonics Inc filed Critical Cyberonics Inc
Publication of EP1296743A1 publication Critical patent/EP1296743A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36007—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation of urogenital or gastrointestinal organs, e.g. for incontinence control

Definitions

  • the present invention relates generally to methods and apparatus for treating eating disorders by application of modulating electrical signals to a selected cranial nerve, nerve branch or nerve bundle, and more particularly to techniques for treating patients with overeating disorders, and especially obese patients by application of such signals bilaterally to thepatient's vagus nerve with one or more neurostimulating devices.
  • modulating electrical signals to a selected cranial nerve, nerve branch or nerve bundle
  • techniques for treating patients with overeating disorders, and especially obese patients by application of such signals bilaterally to thepatient's vagus nerve with one or more neurostimulating devices.
  • Morbid obesity is defined as having a body mass index of more than forty, or, as is more commonly understood, being more than one hundred pounds overweight for a person of average height. This data is alarming for numerous reasons, not the least of which is it indicates an obesity epidemic. Many health experts believe that obesity is the first or second leading cause of preventable deaths in the United States, with cigarette smoking either just lagging or leading. A recent study from the Kaiser HMO system has demonstrated that morbid obesity drastically increases health care costs (Journal of the American Medical Association (JAMA)). It is the consequences of being overweight that are most alarming.
  • JAMA American Medical Association
  • Obesity is asserted to be the cause of approximately eighty percent of adult onset diabetes in the United States, and of ninety percent of sleep apnea cases. Obesity is also a substantial risk factor for coronary artery disease, stroke, chronic venous abnormalities, numerous orthopedic problems and esophageal reflux disease. More recently, researchers have documented a link between obesity, infertility and miscarriages, as well as post menopausal breast cancer.
  • the '480 patent discloses that treatment for eating disorders in general, and obesity and compulsive overeating disorder in particular, may be carried out by selectively applying specially adapted modulating electrical signals to the patient's vagus nerve by a neurostimulator which is preferably totally implanted in the patient, but may alternatively be employed external to the body or even percutaneously.
  • the modulating signals themselves may be stimulating or inhibiting with respect to the electrical activity of the vagus nerve, but for purposes of that patent, both cases were sometimes included within the term "stimulating". In essence, stimulation of vagal activity could cause more neural impulses to move up the nerve whereas inhibition of vagal activity could block neural impulses from moving up the nerve.
  • the modulating signals can be used to produce excitatory or inhibitory neuro- transmitter release.
  • strategies for vagal modulation including adjusting the parameters for electrical stimulation of the vagus nerve, nerve fibers or nerve bundle, depend on a number of factors. Among these are considerations of which part(s) of the nerve or the nerve fibers are to be subjected to the modulating signals; whether the patient experiences a "feeling" or sensation at the onset of the disorder or a symptom of the disorder which can be used to activate the neurostimulation generator or, alternatively, a physiologic signal is generated which can be detected and employed to trigger the modulation; and/or whether a "carryover" or refractory period occurs after modulation in which the benefit of the modulation is maintained.
  • appropriate setting of pulse width and amplitude of the stimulating (modulating) signal at the output of the neurostimulator, applied via electrode(s) to the vagus nerve might allow particular fibers of the nerve to be selectively stimulated.
  • the precise signal pattern to be used such as the length of the time intervals in which the signal is on and off, might be adjusted to the individual patient and the particular eating disorder being treated.
  • vagal stimulation could be used to produce appetite suppression by causing the patient to experience satiety, a sensation of "fullness,” which would naturally result in decreased intake of food and consequent weight reduction. In effect, the brain perceives the stomach to be full as a result of the treatment.
  • an implantable neurostimulator included a signal generator or electronics package adapted to generate an electrical output signal in the form of a sequence of pulses, with parameter values programmable by the attending physician within predetermined ranges for treating the disorder, and a lead/ electrode system for applying the programmed output signal to the patient's vagus nerve. Calibration of the overall treatment system for a particular patient was to be performed by telemetry by means of an external programmer to and from the implant.
  • the implanted electronics package might be externally programmed for activation upon occurrence of a predetermined detectable event, or, instead might be periodically or continuously activated, to generate the desired output signal with parameter values programmed to treat obesity by modulating vagal activity so as to produce a sensation of satiety.
  • the stimulus generator or electronics package might be located external to the patient, with only an RF coil, rectifier and the lead/nerve electrode assembly implanted; or with the lead implanted percutaneously through the skin and to the nerve electrode.
  • the latter technique was least preferred because special precautions would be needed to avoid possible infection via the path from outside the body to the nerve along the lead.
  • the stimulus generator of the neurostimulator is implanted in a convenient location in the patient's body, such as in the abdomen in relatively close proximity to the stimulating electrode system and, if applicable, to the detecting system.
  • the patient's food intake i.e., the quantity of food consumed
  • the swallows could be summed over a preselected time interval to provide an indication or estimate of the amount of food consumed in the selected interval. Modulation of vagal activity would then be initiated i f the summation exceeded a predetermined threshold level.
  • the stimulating electrode (nerve electrode, e.g., a cuff) would be implanted about the vagus nerve or a branch thereof in the esophageal region slightly above the stomach, and the vagal stimulation applied to produce or induce satiety.
  • the patient would experience a satisfied feeling of fullness at a level of consumption sufficient to maintain physiologic needs but supportive of weight reduction.
  • the appropriately programmed output signal of the neurostimulator is applied periodically to modulate the patient's vagus nerve activity, without regard to consumption of a particular quantity of food, except perhaps at prescribed mealtimes during normal waking hours according to the patient's circadian cycle.
  • the intent of such treatment was to suppress the patient's appetite by producing the sensation of satiety between normal mealtimes.
  • the neurostimulator electronics package could be implemented for manual activation of the output signal by the patient, as by placement of an external magnet over the implanted device (to close a switch), or by tapping the region over the device (to cause it to respond to the sound or vibration), or by use of an RF transmitter, for example.
  • Manual activation would be useful in situations where the patient has an earnest desire to control his or her eating behavior, but requires supportive measures because of a lack of sufficient will power or self-control to refrain from the compulsive behavior, such as binge eating or simply overeating, in the absence of the neurostimulation device.
  • vagus nerve is the dominant nerve of the gastrointestinal (GI) tract (see, e.g. , GI) tract (see, e.g. , GI) tract (see, e.g. , GI) tract (see, e.g. , GI) tract (see, e.g. , GI) tract (see, e.g. , GI) tract (see, e.g. , GI) tract (see, e.g. , GI) tract.
  • a right and a left vagus connect the GI tract to the brain. After leaving the spinal cord, the vagal afferents transport information regarding the GI tract to the brain. In the lower part of the chest, the left vagus rotates, becomes the anterior vagus, and innervates the stomach. The right vagus rotates to become the posterior vagus, which branches into the celiac division and innervates the duodenum and proximal intestinal tract.
  • vagus is often though of as a motor nerve which also carries secretory signals
  • 80% of the nerve is sensory consisting of afferent fibers (see, e.g., Grundy et al., "Sensory afferents from the gastrointestinal tract," Handbook of Physiology, Sec. 6, S.G., Ed., American Physiology Society, Bethesda, Maryland, 1989, Chapter 10). While the exact mechanisms that make us feel full are still being determined, much information has been accumulated. Satiety signals include the stretch of mechanoreceptors, and the stimulation of certain chemosensors ( "A Protective Role for Vagal Afferents: An Hypothesis.
  • vagal afferent fibers are an important source of information to the brain regarding the quantity and quality of the ingests.
  • the present invention is based on the applicants' study of particular methods and techniques of vagus nerve stimulation after numerous studies that have indicated the vagus to be an important nerve transporting satiety signals from the gut to the brain.
  • vagus nerve is the "information superhighway" for conducting signals from agents such as cholecystokinin and enterostatin. It remains to be determined whether and how such signals could be mimicked by using vagal nerve stimulation. Greater attention to use of vagal stimulation in treating obesity is also prompted in part by the knowledge that vagal nerve stimulation has been shown to be safe and effective when used long-term to treat epilepsy. That is to say, the regimen in studies involving use of vagal stimulation techniques to treat obesity would not involve the extreme measures or short- and long- term side effects on the patient that have characterized treatment methods of the type described above in the background section.
  • a method of treating patients for obesity includes performing bilateral stimulation of the patient's vagus nerve by applying a stimulating electrical signal to the right and left vagi, wherein the parameters of the signal are predetermined to produce a sensation of satiety in the patient.
  • the signal could be applied synchronously to the right and left vagi or asynchronously.
  • the stimulating electrical signal is preferably a pulse signal which is applied intermittently to the right and left vagi according to the duty cycle of the signal (i.e., its on and off times).
  • the intermittent application of the stimulating electrical signal is preferably chronic, rather than acute. Nevertheless, it is possible that the bilateral stimulation could be delivered continuously to the right and left vagi to achieve some success in the treatment, and/or that acute application might suffice in some circumstances.
  • the stimulating electrical signal applied acutely to the right and left vagi during a customary mealtime, or from a short time preceding and/or following the mealtime, according to the patient's circadian cycle could be somewhat effective in certain cases.
  • an automatic delivery of bilateral intermittent stimulation is preferred, it is also possible that application of the stimulating electrical signal to the right and left vagi might be controlled by an external commencement signal administered by the patient, as by use of an external magnet brought into proximity with the implanted device.
  • the same stimulating electrical signal is applied to both the right and left vagi, but it may also be possible to apply a different stimulating electrical signal to the right vagus from the stimulating electrical signal applied to the left vagus.
  • two separate nerve stimulator generators may be implanted for stimulating the left and right vagi, a single nerve stimulator generator may be implanted for bilateral stimulation if the same signal is to be applied to both the left and right branches of the vagus, whether delilvered synchronously or asynchronously to the vagi.
  • the stimulating electrical signal is applied at the supradiaphragmatic position of the left and right vagi.
  • the stimulating signal is characterized by a cu ⁇ ent magnitude below a predetermined physiological response to stimulation called the retching level of stimulation of the patient. This is to assure that the patient will not suffer from nausea during the periods of vagus nerve stimulation.
  • the most preferred method of treating patients for obseity includes stimulating the left and right branches of the patient's vagus nerve simultaneously with electrical pulses in a predetermined sequence of a first period in which pulses are applied continuously, alternating with a second period in which no pulses are applied, and in which the electrical pulses are applied to the vagus nerve at a supradiaphragmatic location.
  • the pulses preferably have an electrical current magnitude not exceeding about 6 ma, but in any event, the magnitude is preselected to be less than the level that would induce retching in the patient as determined at the time of the initial implant(s).
  • the pulse width is adjusted to a value not exceeding about 50Q ms, and the pulse repetition frequency is set at about 20-30 Hz.
  • the second period is preferably about 1.8 times as long as the first period in the alternation of application of the stimulating pulses (i.e., the on/off duty cycle is at a ratio of 1 : 1.8).
  • the pulse parameters including on time and off time are programmable by the implanting physician, using an external programmer.
  • Apparatus according to the invention for treating patients suffering from obesity eating disorder includes implantable neurostimulator device means for simultaneously stimulating left and right branches of the patient's vagus nerve with electrical pulses in a predetermined sequence of a first period in which pulses are applied continuously, alternating with a second period in which no pulses are applied; and electrode means for implantation on the right and left branches in a supradiaphragmatic position.
  • the patient is treated with bilateral stimulation of the right and left vagi branches at the supradiaphragmatic position of the vagus nerve, using neurostimulators (e.g., the NCP® generator available from Cyberonics, Inc. of
  • a standard Cyberonics Bipolar Lead nerve electrode for example, is attached to the nerve generator after the patient's eating behavior is standardized and a stable dietary pattern is observed.
  • the dietary pattern included twice- a-day feedings of approximately 400 grams of solid food with one scoop of soft meat product added to make the food more edible.
  • a threshold referred to herein as the retching threshold was documented while the animal was under anesthesia, based on the threshold value of the stimulus output current of the device at which the animal exhibited a retching or emetic response. The amount of current was adjusted to determine this threshold.
  • Other parameters were left fixed at a frequency of 30 Hertz (Hz), apulse width of 500 milliseconds (ms), and an on/off cycle of one minute on and 1.8 minutes off.
  • the animals were allowed to stabilize. Once eating behavior returned to preoperative levels the vagal nerve stimulators were turned on in two canines. These two were given chronic intermittent bilateral nerve stimulation over a twenty-four hour period. Initial amplitude was set at approximately 1.0 to 1.5 milliamperes (mA) below the retching threshold, and adjusted thereafter. The retching thresholds in mA increased over a period of days.
  • both nerve stimulator generators were turned back on and, after a period of several days of the bilateral stimulation, each of the animal's eating behavior reverted to the slowed pace that had been observed in the postoperative period following such stimulation.
  • the characterization of the bilateral stimulation as being "intermittent" is made in the sense that the stimulation was performed following a prescribed duty cycle of application of the signal.
  • the latter is a pulse signal, and is applied with a prescribed or preset or predetermined on-time of the pulses, followed by a prescribed or preset or predetermined off-time of the pulses, which could be the same as but in general is different from the on-time. It is possible, however, depending upon other parameters of the electrical pulse signal, that a continuous signal might be effective to produce the slowed eating behavior. It is also possible to use a single implanted nerve stimulator (pulse generator) with appropriate duty cycle to provide the bilateral stimulation of both vagal branches, right and left. Or the stimulation may be different for each branch and use different implanted stimulators.
  • implanted stimulators are preferred, it is also possible to treat patients receiving clinical or in-hospital treatment by means of external devices that provide vagal stimulation via leads and electrodes implanted in the patient. Wholly implanted devices are preferred, however, because they allow patients to be completely ambulatory, and without interfering with routine daily activities.
  • Some differences from stimulator to stimulator in magnitude of current in the pulses of the electrical stimulation signal may be observed, and may be attributable to things such as patient impedance, variation of the vagus nerve from right to left or between patients, and variation in contact between the vagus and the electrode implanted thereon from implant to implant.

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  • Health & Medical Sciences (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Electrotherapy Devices (AREA)

Abstract

L'invention concerne un procédé de traitement des patients atteints d'hyperphagie boulimique, consistant à stimuler simultanément les branches gauche et droite du nerf vague du patient à l'aide d'impulsions électriques dans une séquence prédéterminée d'une première période durant laquelle les impulsions sont appliquées de manière continue, en alternance avec une seconde période durant laquelle aucune impulsion n'est appliquée. Les impulsions électriques sont de préférence appliquées au nerf vague à un emplacement supradiaphragmatique.
EP00955908A 2000-07-06 2000-07-06 Traitement de l'obesite par stimulation bilaterale du nerf vague Withdrawn EP1296743A1 (fr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US2000/040301 WO2002004068A1 (fr) 2000-07-06 2000-07-06 Traitement de l'obesite par stimulation bilaterale du nerf vague

Publications (1)

Publication Number Publication Date
EP1296743A1 true EP1296743A1 (fr) 2003-04-02

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EP00955908A Withdrawn EP1296743A1 (fr) 2000-07-06 2000-07-06 Traitement de l'obesite par stimulation bilaterale du nerf vague

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EP (1) EP1296743A1 (fr)
JP (1) JP2004502506A (fr)
AU (1) AU782785B2 (fr)
CA (1) CA2401098C (fr)
WO (1) WO2002004068A1 (fr)

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EP1357970B1 (fr) * 2001-01-02 2011-11-02 Cyberonics, Inc. Traitement de l'obesite par stimulation des nerfs sous diaphragmatiques

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US7561919B2 (en) 2002-11-14 2009-07-14 Brainsgate Ltd. SPG stimulation via the greater palatine canal
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US9675796B2 (en) 2013-11-10 2017-06-13 Brainsgate Ltd. Implant and delivery system for neural stimulator
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US11154238B2 (en) 2015-08-07 2021-10-26 Electroceuticals, Llc Systems, methods and apparatuses for providing bioelectronic neurocode-based therapies to mammals

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EP1357970B1 (fr) * 2001-01-02 2011-11-02 Cyberonics, Inc. Traitement de l'obesite par stimulation des nerfs sous diaphragmatiques

Also Published As

Publication number Publication date
WO2002004068A1 (fr) 2002-01-17
CA2401098A1 (fr) 2002-01-17
JP2004502506A (ja) 2004-01-29
CA2401098C (fr) 2012-03-13
AU6802800A (en) 2002-01-21
AU782785B2 (en) 2005-08-25

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