Non-Invasive Neuromodulation Device for the Treatment of Alcohol Use Disorder

Abstract Alcohol use disorderAUDis a major public health concernaffecting overmillion AmericansAUD is a highly disabling disease associated with many physical and psychiatric co morbiditiesand excessive alcohol consumption is now the third leading preventable cause of death in the U SCurrent AUD interventions include pharmacologic treatment and behavioral therapieshoweverthese are not very effectivehaving high rates of relapse soon after initial successful treatmentA large evidence base shows that an exaggerated central nervous system response to alcohol related cues is a key phenomenon in alcohol dependence and relapseWith longterm AUDneutral cognitive or environmental cues can evoke a supraphysiological dopamineDAresponse in the mesolimbic circuit in the absence of the direct alcohol effectThe magnitude of this conditioned reward circuitry response has subsequently been hypothesized to be associated with cravingultimately increasing the likelihood of relapseInvasive neuromodulation techniques that target the mesolimbic circuitry in the mid brain have demonstrated substantial promise in reducing craving and alcohol consumption in multiple case studiesHoweverthe invasive surgical procedure as well as infectionand implant related adverse events limit acceptabilityPeripheral nerve stimulationwhich may be a more acceptable therapy to patientshas also been shown to directly regulate the mesolimbic DA pathway and impede drug induced effectsTo take advantage of this craving regulatory circuitTheraNova has developed Leo Sa non invasiveportable transcutaneous electrical nerve stimulation device for the treatment of AUDBy providing a safediscreeteasy to useand effective therapy that targets the mesolimbic circuitLeo S may substantially improve initial treatment outcomes as well as future relapse ratesLeo S device has demonstrated early feasibility through two pilot studies in healthy human subjectsThe overall goal of this Phase I proposal is to verify safety and patient acceptability for daily Leo S use as an AUD treatmentIn Specific Aimapatient study will be conducted to optimize the device designTwo skin contacting electrode designs will be evaluated to maximize patient acceptability while providing consistent nerve stimulationIn Specific Aimwe will use the optimal design from Aimto conduct apatientcross overhome use studyPatients will have a one week control period with no treatment followed by two weeks of daily Leo S treatmentOur primary endpoints will be device acceptability and safety for homeuseWe will also evaluate the short term treatment effectiveness for reducing alcohol craving and consumptionIn additionthese studies will provide data on recruitmentattritionand effect size that will be critical for powering a pivotal study to validate the long term effects of Leo S treatment on craving and alcohol consumption in Phase IIOur goal is to provide a therapy thatalone or in conjunction with current treatmentseffectively reduces cravingprevents relapseand promotes abstinence from excessive alcohol consumptionThis will provide AUD patients with a much needed therapy to help eliminate the consequences of prolonged AUD Narrative Alcohol use disorderAUDis a major public health concern that affects overmillion Americans and is now the third leading preventable cause of death in the United StatesCurrent interventions include pharmacologic treatment and behavioral therapieshoweverhigh rates of relapse soon after initial successful treatment are a common problemThis Phase I SBIR project proposes the development of a non invasive transcutaneous electrical nerve stimulation device to provide a therapy thatalone or in conjunction with current treatmentseffectively reduces cravingprevents relapseand promotes abstinence from excessive alcohol consumption