CTN-0068: Accelerated Development of Additive Pharmacotherapy Treatment (ADAPT-2) for Methamphetamine Use Disorder
Principal Investigator
Madhukar Trivedi, MD
University of Texas Southwestern Medical Center
Madhukar.Trivedi@utsouthwestern.edu
Co-Lead Investigator & Project Director
Robrina Walker, PhD
University of Texas Southwestern Medical Center
Robrina.Walker@utsouthwestern.edu
This double-blinded, placebo-controlled study will investigate the effectiveness and safety of a combination pharmacotherapy for adults with moderate to severe methamphetamine use disorder. A total of 370 treatment-seeking participants will be randomized to either the 1) Active Medication Condition and receive injections of extended release naltrexone (Vivitrol®) plus 450 mg of once-daily oral extended-release bupropion tablets or the 2) matching placebo arm and receive injections of placebo plus once-daily oral placebo tablets. Injections will be administered every 3 weeks. During this 12-week medication phase, participants may be re-randomized to another arm, as determined by the a priori adaptive aspect of the study design; participants appearing to respond well to their originally-assigned arm will not be re-randomized. The primary goal of the study is to evaluate the effectiveness of the active medication condition compared to the placebo arm. After the medication phase, participants will complete a medication taper and post-medication phase follow-up visits during weeks 13 and 16.
Primary Findings
Among adults with methamphetamine use disorder, the response over a period of 12 weeks among participants who received extended-release injectable naltrexone plus oral extended-release bupropion was higher than that among participants who received placebo. A total of 403 participants were enrolled in stage 1, and 225 in stage 2. In the first stage, 18 of 109 participants (16.5%) in the naltrexone-bupropion group and 10 of 294 (3.4%) in the placebo group had a response. In the second stage, 13 of 114 (11.4%) in the naltrexone-bupropion group and 2 of 111 (1.8%) in the placebo group had a response. The weighted average response across the two stages was 13.6% with naltrexone-bupropion and 2.5% with placebo, for an overall treatment effect of 11.1 percentage points (Wald z-test statistic, 4.53; P<0.001). Adverse events with naltrexone-bupropion included gastrointestinal disorders, tremor, malaise, hyperhidrosis, and anorexia. Serious adverse events occurred in 8 of 223 participants (3.6%) who received naltrexone-bupropion during the trial.
Primary Outcomes Article: Trivedi MH, et al. Bupropion and Naltrexone in Methamphetamine Use Disorder. New England Journal of Medicine 2021;384:140-153. [get article]
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