Opioid use disorder (OUD) has become a public health emergency. Approximately 2.6 million Americans suffered from OUD in 2016. OUD can be lethal, with opioid overdose causing more than 115 deaths in the U.S. each day. Evidence-based approaches for treating OUD include several medication-assisted treatments (MATs): methadone, buprenorphine/naloxone (BUP/NAL), and extended-release naltrexone (NTX). While MATs are effective at reducing illicit opioid use and overdose deaths, it is well-established that withdrawal and craving are highest in the initial weeks, making this a high-risk period for treatment dropout, relapse, and overdose. In fact, clinical studies have shown that long-term MAT treatment retention rates are generally at or below 50%. Thus, patients suffering from OUD could benefit from more comprehensive therapies. With a superior safety profile, accessibility in office-based settings, and the ability for patients to initiate treatment earlier in the withdrawal phase, BUP/NAL is now the most commonly prescribed MAT. However, BUP/NAL retention rates are only ~70- 80% at 30 days and ~30-43% at 6 months. While the specific factors that determine poor retention rates are not clearly defined, both opioid withdrawal and craving in the initial treatment weeks are contributors to dropout for all MATs. For studies that compared BUP/NAL and NTX, opioid craving and heroin use were significantly higher for BUP/NAL. Thus, adjunct therapies that can be used in combination with MATs, in general, and BUP/NAL, in particular, to reduce early opioid withdrawal and craving may improve treatment retention. Recent research has shown that stimulation of a peripheral nerve significantly modulates withdrawal- and craving-related responses for opioids, alcohol, cocaine, and tobacco. We, therefore, hypothesize that peripheral nerve stimulation can be a potent adjunct treatment to MATs through its direct effects on withdrawal and craving. TheraNova has developed the EMPOWER Neuromodulation System, a portable, non-invasive transcutaneous electrical nerve stimulation (TENS) device for the treatment of OUD. EMPOWER consists of a portable electrical signal generator that is connected to electrodes placed on the skin to stimulate nerves through the skin. The goal of this proposal is to conduct a pilot clinical evaluation of EMPOWER as an adjunct therapy to BUP/NAL for OUD treatment. We will conduct a 3-week, blinded, sham-controlled clinical study in 40 participants who are initiating BUP/NAL treatment for OUD. Participants will self-administer a daily treatment session (30 min) for 21 days. To investigate effectiveness (Specific Aim 1), we will compare opioid withdrawal symptoms, craving, and use, as well as treatment retention for the active and sham treatment groups. To investigate acceptability (Specific Aim 2), we will evaluate participant-rated usability of EMPOWER, compliance with the treatment regimen, and overall treatment satisfaction. After demonstrating feasibility in this study, we will conduct a longer-term RCT in Phase II to evaluate the effect of the EMPOWER therapy on BUP/NAL treatment retention at six months. We expect that this pivotal study will support FDA clearance for EMPOWER through the de novo 510(k) pathway.
Effectively treating opioid use disorder (OUD) has become a public health emergency. While medication-assisted treatments (MATs) can be effective, for all MATs it is well-established that withdrawal and craving are highest in the initial weeks, making this a high-risk period for treatment dropout. This Phase I SBIR project proposes the development of a non-invasive transcutaneous electrical nerve stimulation device to provide a therapy that, in conjunction with MATs, can effectively reduce opioid withdrawal and craving to promote retention in treatment.
