Active versus sham transcranial direct current stimulation (tDCS) as an adjunct to varenicline treatment for smoking cessation: Study protocol for a double-blind single dummy randomized controlled trial

Background Smoking is a chronic and relapsing disease, with up to 60% of quitters relapsing within the first year. Transcranial Direct Current Stimulation (tDCS), targets cortical circuits and acutely reduces craving and withdrawal symptoms among cigarette smokers. However, the efficacy of tDCS as an adjunct to standard smoking cessation treatments has not been studied. This study aims to investigate the effectiveness of tDCS in combination with varenicline for smoking cessation. We hypothesize that active tDCS combined with varenicline will improve cessation outcomes compared to sham tDCS combined with varenicline. Methods This is a double-blind, sham-controlled randomized clinical trial where fifty healthy smokers will be recruited in Toronto, Canada. Participants will be randomized 1:1 to either active tDCS (20 minutes at 2 mA) or sham tDCS (30 seconds at 2 mA, 19 minutes at 0 mA) for 10 daily sessions (2 weeks) plus 5 follow up sessions, occurring every two weeks for 10 weeks. All participants will be given standard varenicline treatment concurrently for the 12-week treatment period. The primary outcome is 30 day continuous abstinence at end of treatment, confirmed with urinary cotinine. Measurements made at each study visit include expired carbon monoxide, self-reported craving and withdrawal. Three magnetic resonance imaging (MRI) scans will be conducted: two at baseline and one at end of treatment, to assess any functional or structural changes following treatment. Discussion For every two smokers who quit, one life is saved from a tobacco-related mortality. Therefore, it is important to develop new and more effective treatment approaches that can improve and maintain long-term abstinence, in order to decrease the prevalence of tobacco-related deaths and disease. Furthermore, the addition of longitudinal neuroimaging can shed light on neural circuitry changes that might occur as a result of brain stimulation, furthering our understanding of tDCS in addiction treatment. Trial registration This trial has been registered with Clinicaltrials.gov: NCT03841292 since February 15th 2019 (https://clinicaltrials.gov/ct2/show/NCT03841292)–retrospectively registered.