Electronic cigarettes as a harm reduction strategy for combustible cigarette smoking among people in opioid use disorder treatment programs: protocol for an open-label two-arm randomized controlled trial

Combustible cigarette smoking among people in opioid use disorder treatment programs is exceptionally high. Electronic cigarettes may deliver nicotine while replicating smoking rituals, offering a potential harm-reduction alternative to nicotine replacement therapy. This trial compares the effectiveness of a standardized research electronic cigarette developed by the National Institute on Drug Abuse, plus telehealth counseling, versus combination nicotine replacement therapy plus telehealth counseling on combustible cigarette abstinence and reductions in cigarettes-per-day among people in opioid use disorder treatment programs who smoke combustible cigarettes. This multi-site, open-label randomized controlled trial randomizes 302 people in opioid use disorder treatment programs who smoke combustible cigarettes to electronic cigarettes or nicotine replacement therapy (ratio 1:1). All participants receive up to five telehealth counseling sessions grounded in motivational interviewing and harm-reduction principles. The primary outcome is the proportion of participants achieving 100% cigarettes-per-day reduction at the end of the 8-week intervention, verified by exhaled carbon monoxide level (< 6 ppm). Secondary outcomes include the proportion of participants achieving 100% cigarettes-per-day reduction at 6-month follow-up; reduction in smoking toxicant exposure, measured by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, NNAL, in urine at 8 weeks vs. baseline among participants reporting ≥ 50% cigarettes-per-day reduction; cigarettes-per-day reduction at end of intervention and at 6 months; and other self-reported health outcomes (e.g., health-related quality of life). Recruitment and treatment are ongoing. We hypothesize higher combustible cigarette abstinence and greater cigarettes-per-day reduction in the electronic cigarettes arm compared with the nicotine replacement therapy arm, with parallel improvements in toxicant exposure and secondary outcomes. Findings will clarify whether electronic cigarettes combined with telehealth counseling may constitute a viable harm-reduction strategy for adults in opioid use disorder treatment programs who smoke combustible cigarettes and may inform future tobacco treatment guidelines. ClinicalTrials.gov Identifier: NCT05722561