Non-invasive Neuromodulation Device for Decreasing Withdrawal Symptoms and Craving during Treatment of Opioid Use Disorder

Abstract Opioid use disorderOUDhas become a public health emergencyApproximatelymillion Americans suffered from OUD inOUD can be lethalwith opioid overdose causing more thandeaths in the U Seach dayEvidence based approaches for treating OUD include several medication assisted treatmentsMATsmethadonebuprenorphine naloxoneBUP NALand extended release naltrexoneNTXWhile MATs are effective at reducing illicit opioid use and overdose deathsit is well established that withdrawal and craving are highest in the initial weeksmaking this a high risk period for treatment dropoutrelapseand overdoseIn factclinical studies have shown that long term MAT treatment retention rates are generally at or belowThuspatients suffering from OUD could benefit from more comprehensive therapiesWith a superior safety profileaccessibility in office based settingsand the ability for patients to initiate treatment earlier in the withdrawal phaseBUP NAL is now the most commonly prescribed MATHoweverBUP NAL retention rates are onlyatdays andatmonthsWhile the specific factors that determine poor retention rates are not clearly definedboth opioid withdrawal and craving in the initial treatment weeks are contributors to dropout for all MATsFor studies that compared BUP NAL and NTXopioid craving and heroin use were significantly higher for BUP NALThusadjunct therapies that can be used in combination with MATsin generaland BUP NALin particularto reduce early opioid withdrawal and craving may improve treatment retentionRecent research has shown that stimulation of a peripheral nerve significantly modulates withdrawaland craving related responses for opioidsalcoholcocaineand tobaccoWethereforehypothesize that peripheral nerve stimulation can be a potent adjunct treatment to MATs through its direct effects on withdrawal and cravingTheraNova has developed the EMPOWER Neuromodulation Systema portablenon invasive transcutaneous electrical nerve stimulationTENSdevice for the treatment of OUDEMPOWER consists of a portable electrical signal generator that is connected to electrodes placed on the skin to stimulate nerves through the skinThe goal of this proposal is to conduct a pilot clinical evaluation of EMPOWER as an adjunct therapy to BUP NAL for OUD treatmentWe will conduct aweekblindedsham controlled clinical study inparticipants who are initiating BUP NAL treatment for OUDParticipants will self administer a daily treatment sessionminfordaysTo investigate effectivenessSpecific Aimwe will compare opioid withdrawal symptomscravingand useas well as treatment retention for the active and sham treatment groupsTo investigate acceptabilitySpecific Aimwe will evaluate participant rated usability of EMPOWERcompliance with the treatment regimenand overall treatment satisfactionAfter demonstrating feasibility in this studywe will conduct a longer term RCT in Phase II to evaluate the effect of the EMPOWER therapy on BUP NAL treatment retention at six monthsWe expect that this pivotal study will support FDA clearance for EMPOWER through the de novokpathway Narrative Effectively treating opioid use disorderOUDhas become a public health emergencyWhile medication assisted treatmentsMATscan be effectivefor all MATs it is well established that withdrawal and craving are highest in the initial weeksmaking this a high risk period for treatment dropoutThis Phase I SBIR project proposes the development of a non invasive transcutaneous electrical nerve stimulation device to provide a therapy thatin conjunction with MATscan effectively reduce opioid withdrawal and craving to promote retention in treatment