Repetitive transcranial magnetic stimulation for stimulant use disorders (STIMULUS): protocol for a multi-site, double-blind, randomized controlled trial

BACKGROUND: Cocaine and methamphetamine use disorders (CcUD/MtUD) have serious public health, medical, and psychiatric consequences. Yet, there are no U.S. Food and Drug Administration (FDA) approved treatments available. The STIMULUS study is a multi-site trial, sponsored by the National Drug Abuse Treatment Clinical Trials Network (CTN), that aims to investigate the feasibility and preliminary efficacy of repetitive transcranial magnetic stimulation (rTMS) as a potential treatment for moderate to severe CcUD/MtUD. METHODS: The study is a double-blind, sham-controlled trial seeking to recruit 160 participants with a current moderate to severe CcUD or MtUD diagnosis, randomized to receive active rTMS (10-Hz stimulation at 120% motor threshold over the left dorsolateral prefrontal cortex) or sham. Feasibility is assessed by a target of at least 20 treatment sessions administered within an 8-week period. Additionally, the study aims to evaluate the efficacy of rTMS in reducing stimulant use and craving, the impact of rTMS on mood, anxiety, sleep, and other measures, and the utility of electroencephalography as a treatment response biomarker. DISCUSSION: Studies exploring rTMS for stimulant use disorders remain limited by small sample sizes, as well as great heterogeneity in defined study population, treatment parameters, retention in treatment, and number of sessions. In this paper, we highlight key study design decisions, such as safety, sham procedure, and schedule flexibility. CONCLUSION: We hope that the data collected will lay the groundwork for a robust randomized controlled trial of rTMS as a therapeutic intervention for individuals with CcUD/MtUD. TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov . Identifier: NCT04907357. TRIAL DATA SET: https://clinicaltrials.gov/study/NCT04907357?tab=table . PROTOCOL: Version 7.0, 11/10/2023.