This application proposes to conduct a randomized, controlled clinical trial to test the efficacy and safety of the Bridge Device (BD) when used for the treatment of opioid withdrawal. The BD is an FDA cleared tool that is currently marketed for the treatment of opioid withdrawal; preliminary evidence suggests it is effective and has a low risk for adverse effects. However, the product has not been tested against a sham control condition when used for opioid withdrawal treatment. Descriptive data provide evidence that it has effectiveness in suppressing opioid withdrawal, but there is a need to test the device under controlled conditions. In addition to testing the BD to a sham condition (SBD), the study includes a third condition – lofexidine. This is an FDA-approved medication for the treatment of opioid withdrawal, and this study will be the first direct comparison of two available non-mu opioid approaches that can be used to help transition patients off of opioid physical dependence. Novel mechanisms that assist in transitioning a person from physical dependence on opioids to a non-dependent state are needed – to address a patient-centered desire to live without maintenance on opioid agonist treatment (OAT), and/or to aid in the transition to antagonist treatment. Given the accumulating evidence for the efficacy of naltrexone (NTX), and especially extended release NTX, new and innovative ways to help patient stabilize on antagonist treatment are needed. The BD may serve a useful role in this process. The device is a percutaneous nerve field stimulator that has 4 electrodes placed on/near the ear, with wires to a small device that is worn behind the ear. The device targets 4 cranial nerves (V, VII, IX, and X) that have auricular branches, and it provides alternating low-grade electrical frequencies to these nerves as a means for peripheral stimulation of the specific cranial nerves. Stimulation by the device is hypothesized to provide central nervous modulation of pain paths. When used clinically, the device is worn continuously for 5 days, and reports of its use indicate that it provides relief of opioid withdrawal within approximately an hour of placement. The primary goal of this study is to demonstrate that the BD is more effective than a sham control condition in suppressing opioid withdrawal signs and symptoms, and a secondary aim is to determine its relative efficacy compared to lofexidine. Participants will be persons physically dependent on opioids, with a diagnosis of OUD, and who agree to reside on a residential unit for the study duration. At the end of the residential stay, participants will be offered oral naltrexone treatment, and the option of transition on to XR-NTX. Given the magnitude of the opioid crisis in the United States, and the need to both expand treatment options as well as mechanisms that can facilitate the transition on to antagonist treatments, the BD has the potential to have substantial impact and public health significance. In addition, expanding the treatment of OUD to effective devices can open up new thinking and approaches that are not based solely on pharmacological approaches to this devastating medical illness.

NARRATIVE This R01 application proposes to conduct a controlled study testing the efficacy of the Bridge Device as a new and novel mechanism to aid in treating the signs and symptoms of opioid withdrawal. The study will be conducted on a supervised residential research unit, and opioid-dependent participants will undergo opioid withdrawal while receiving either the device, an FDA-approved medication for the treatment of opioid withdrawal, or placebo. Participants and staff will not know to which group they are assigned.