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

Abstract

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.

Fig 1. Flow diagram of proposed study.

Fig 2. Schedule of enrolment interventions and assessments.

*Baseline MRI Scans will be counterbalanced such that participants will be undergoing an abstinence scan and a satiated scan within one week of each other. ** Daily tDCS stimulation over the first 2 weeks. List of abbreviations: MRI = functional magnetic resonance imaging; Eot = end of treatment; PHQ-9 = Patient Health Questionnaire–validated self-completed measure of depressive symptoms mapped on to DSM-IV criteria; QSU-brief = 10-item Questionnaire of Smoking Urges; AUDIT = Alcohol Use Disorders Identification Test; FTND = Fagerstrom Test for Nicotine Dependence; EIS = Eysenck Impulsivity Inventory; SSS = Sensation Seeking Scale; PANAS = Positive and Negative Affect Schedule; State Trait = State Trait Anxiety; POMS = Profile of Mood States.; BOLD = Blood oxygen level dependent signal, functional MRI measure of blood flow; Abs = MRI scan conducted following overnight nicotine abstinence (of at least 10 hours); Sat = MRI scan conducted following nicotine satiety (within 1–2 hours of smoking a cigarette).

Fig 3. Estimated electrical field for tDCS stimulation (using SimNIBs).

Fig 4. Design for smoking cue reactivity task paradigm (MRI task).

During each MRI scan, participants will be presented images for approximately 7 minutes whilst being asked regarding their cigarette craving in between the blocks. The smoking block will consist of pictures related to smoking whilst the neutral block will have neutral images. Each block will last for 35 seconds for a total of 6 blocks. Blood oxygen level signal will be measured during this task. *Photos were taken from the Geneva Smoking Pictures (Khazaal et al. 2012).