PROJECT SUMMARY Background. Buprenorphine (BUP) is an effective medication for opioid use disorder (OUD) but dropout rates are high during the stabilization phase (months 1-3). Posttraumatic stress disorder (PTSD) is common in individuals with OUD and makes retention in treatment even more challenging because of hyperarousal and intense negative affect that greatly increase risk for urges to “self-medicate”. Transcutaneous auricular neurostimulation (tAN) of the vagus nerve has shown promise for alleviating symptoms of PTSD and opioid withdrawal symptoms (OWS) but its effects have yet to be tested in a sample starting BUP therapy with these co-occurring concerns. Aims. We will conduct an open-label trial (Aim 1; 2-year UG3; N = 20) of the Sparrow Ascent System—a patient-administered, ear worn device that delivers electrical stimulation to branches of the vagus and trigeminal nerves—to evaluate the acceptability, tolerability, and feasibility of tAN for patients with co-occurring PTSD/OUD in the context of BUP initiation. We anticipate that more than 50% of the sample will be retained in BUP. Using data from the UG3 study, we will complete FDA pre-submission for the proposed UH3 study to support a PTSD/OUD indication for Sparrow (Aim 2). Then, we will conduct a randomized, intent-to-treat, sham-controlled Phase II clinical trial (Aim 3; 3-year UH3; N = 60) testing the effects of tAN on BUP retention among PTSD/OUD patients to obtain realistic estimates of tAN’s effect size and inform development of a subsequent full-scale clinical trial. We anticipate that active tAN will improve BUP retention relative to sham. Methods. For both studies, we will recruit patients initiating BUP treatment in a community-based clinic and confirm their PTSD/OUD diagnostic status using gold-standard measures. Patients will begin using the Sparrow Ascent device within one week of BUP induction. Participants in the open-label (UG3) study and active tAN (UH3) conditions will receive therapeutic stimulation from Sparrow; those in the sham condition (UH3) will not. During the open-label trial, we will collect self- and provider-reported tolerability and feasibility data. For both studies, we will obtain self-reported and UDS-confirmed substance use, BUP and Sparrow compliance, and self-reported PTSD and OWS severity at weekly research visits over the 3-month active study period. Outcomes. The primary outcome in the UG3 and UH3 studies will be 3-month BUP retention (retained/not retained) as defined by current BUP prescription at the time of data extraction. Key secondary outcomes for the UG3 trial include the acceptability, tolerability, and feasibility of the Sparrow device as an adjunct intervention alleviating symptoms of PTSD and OWS for patients initiating BUP. Key secondary outcomes for the randomized Phase II clinical trial will include weekly substance use with timeline follow-back and UDS results, PTSD symptom severity, opioid withdrawal and craving, and quality of life.

PROJECT NARRATIVE This project is relevant to public health because patients with both opioid use disorder (OUD) and posttraumatic stress disorder (PTSD) are at high risk for dropping out of buprenorphine medication therapy and experiencing overdose. Our phased project will first examine how helpful patients with PTSD and OUD find a device that administers therapeutic electrical stimulation to their vagus and trigeminal nerves through the skin around their ears and then complete FDA pre-submission for using the device with this population more broadly. Finally, we will study how effective the device is for helping patients with PTSD and OUD stay in buprenorphine treatment by comparing the results of those who received therapeutic stimulation versus those who believed that they had but, in fact, did not.