A Randomized Controlled Trial Examining Extended-Injectable Buprenorphine in those who use High Potency Synthetic Opioids

Project Summary Opioid use disorder (OUD) presents a serious public health problem despite available and effective medications for OUD (MOUD). One factor complicating treatment delivery for OUD and contributing to a devasting overdose (OD) crisis is the proliferation of high potency synthetic opioids (HPSO). HPSO are mu opioid agonists estimated to be 50-1000 more potent to morphine that have become increasingly common in illicit drug supplies over the past several years. Despite the ubiquity of HPSO, systematic evaluations of treatment outcomes for those with OUD who use HPSO remain sparse. Further, factors influencing HPSO physiological dependence and withdrawal, and potential biomarkers (body weight, body fat percentage, plasma buprenorphine/norbuprenorphine levels) contributing to individual differences in response to HPSO remain understudied. There is therefore an urgent need to optimize MOUD use in the context of HPSO and enhance understanding of how individual differences in response to HPSO influence clinical outcomes. The use of extended release, injectable buprenorphine (INJ) may improve treatment adherence and confer greater protection from HPSO-related OD compared to sublingual buprenorphine/naloxone (SLB). However, this approach remains understudied in this population. GOALS: The primary objectives of this K23 Mentored Patient Oriented Research Career Development Award proposal are to: Compare abstinence and relapse rates among those with OUD who use HPSO randomized to receive INJ versus SLB during a 2-day inpatient induction (Aims 1a and 1b), Examine the effect of quantitative HPSO level on admission on opioid withdrawal symptoms and dropout during the induction period and (Aim 2), and Explore the relationship between plasma buprenorphine/norbuprenorphine levels on craving, withdrawal, and time to first use (Exploratory Aims). DESIGN: Forty adults with OUD who use HPSO will be admitted for a 2-day inpatient induction period. Following admission on day 1, a COWS score ≥ 6 will prompt administration of 4/1mg SLB. One hour after tolerating this dose, participants will be randomized to receive 1) a 300 mg extended-release buprenorphine injection (INJ; n=20) or 2) or a placebo injection followed by continued titration onto SLB (SLB; n=20). Quantitative HPSO levels (urine derived LC-MS) will be collected on admission. Following discharge, participants will be scheduled for 1-, 2-, 3-, 4-, 8-, and 12-week follow up visits. We hypothesize that the INJ group will have a higher percentage of days abstinent and lower proportion of participants with a sustained relapse than the SLB group across follow up. Further, we hypothesize that quantitative HPSO level on admission will be positively associated with withdrawal severity and dropout during the induction period for both groups. In completing the proposed study, I will gain invaluable training and experience towards my career development goal of becoming an independent clinical researcher.