TDCS Plus Varenicline for Smoking Cessation

Phase 4

Not yet recruiting

• Conditions: Tobacco Smoking; Nicotine Use Disorder; Tobacco Use Disorder; Substance Use Disorders; Nicotine Dependence; Smoking Cessation
• Interventions: Device: Active Transcranial Direct Current Stimulation (tDCS); Drug: Varenicline 1mg BID; Device: Sham Transcranial Direct Current Stimulation (tDCS)

• Registration Number: NCT06798324
• Lead Sponsor: Centre for Addiction and Mental Health

Brief Summary

The goal of this clinical trial is to determine if active transcranial direct current stimulation (tDCS) plus varenicline is an effective, safe and accessible treatment option for smoking cessation. The main questions this trial aims to answer are:

1. Does active tDCS plus varenicline improve short-term and long-term smoking abstinence rates compared to sham tDCS plus varenicline?

2. Are the safety profiles between active tDCS plus varenicline and sham tDCS plus varenicline different?

The tDCS treatment schedule includes 10 daily sessions for the first 2 weeks (M to F), followed by 5 single bi-weekly booster sessions for the remainder of the treatment period. Participants will come in-person for two follow-up sessions to assess smoking behaviour at 6- and 12-months post-treatment.

Detailed Description

Smoking remains the leading cause of lung cancer globally, with cigarette smokers being about 20 times more likely to develop lung cancer than non-smokers. Despite the availability of effective treatments and extensive public health efforts, quitting smoking remains a significant challenge. Varenicline is currently the most effective medication for smoking cessation, yet most users relapse within the first year. No new medications for smoking cessation have come to market in the past two decades, and as such there is a critical need to optimize existing treatments. Combining treatment modalities can produce therapeutic synergism and improve overall treatment outcomes. Non-invasive brain stimulation techniques have become a popular area of research as a treatment option for substance use disorders with growing evidence of their effectiveness for a variety of addictions. One of these techniques, transcranial direct current stimulation (tDCS), has demonstrated potential in modulating the neuroadaptations associated with chronic smoking and relapse risk. A prior pilot study in our lab found that adjunct active tDCS doubled varenicline's effectiveness at end of treatment. Therefore, the objectives for this trial are as follows:

1. To determine the short-term efficacy of active anodal tDCS to the left DLPFC plus varenicline compared to sham tDCS plus varenicline.

2. To determine the effect of active anodal tDCS to the left DLPFC plus varenicline on sustained abstinence over time.

3. To determine the safety of active anodal tDCS to the left DLPFC plus varenicline compared to sham tDCS plus varenicline.

This study will be a double-blind sham-controlled randomized clinical trial whereby 160 daily cigarette smokers will be recruited. After confirming eligibility at an assessment visit, participants will be randomized (1:1) to one of two groups: 1) Experimental group of active tDCS sessions plus 12 weeks of 1 mg varenicline bid (n=80); and 2) Control group of sham tDCS sessions plus 12 weeks of 1 mg varenicline bid (n=80). Participants will start varenicline treatment on the same day as the first tDCS session, and will follow a standard dose escalation schedule. The tDCS treatment schedule includes 10 daily sessions for the first 2 weeks (M to F), followed by 5 in-person bi-weekly booster sessions for the remainder of the treatment period, and then 2 in-person follow-up sessions to assess smoking behaviour at 6- and 12-months post-treatment. At the 1st daily session, participants will come in-person to be trained on using the tDCS device and provided with a study kit including all relevant study equipment. The following 8 daily sessions will occur remotely, and be monitored by research personnel over Webex. The 10th daily tDCS session will occur in-person, with participants returning the study kit. All 5 bi-weekly booster sessions will occur in-person. Total Study duration (with follow-up) is 12 months.

Study Timeline

• Status Verified: 2025-01
• Study First Submitted: 2025-01-08
• Study First Submitted QC: 2025-01-22
• Study First Posted: 2025-01-29
• Last Update Submitted: 2025-02-24
• Last Update Posted: 2025-02-26
• Study Start: 2025-03-01
• Primary Completion: 2028-01-20
• Study Completion: 2028-08-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 160

Inclusion Criteria

• Be able to provide informed written consent
• Stated willingness to comply with all study procedures
• Age 18-85 years
• Smoke ≥ 8 cigarettes per day (CPD)
• Is seeking treatment for tobacco dependence
• Willing to attend the required clinic appointments (Two consecutive weeks, Monday through Friday)
• Otherwise healthy (i.e. not suffering from any major illness/condition that would impact their participation in the study)

Exclusion Criteria

• Use of smoking cessation medication (e.g. buproprion, varenicline, NRT, cytisine) in the past 3 months
• Current regular use of nicotine-containing products besides cigarettes (e.g. electronic cigarettes, etc.)
• Unstable psychiatric illness that would adversely impact study participation and compliance (determined by the QI)
• History of seizures/epilepsy
• Lifetime history of concussions or head traumas
• Current pregnancy or plans to become pregnant
• Current pacemakers or implanted electrical devices
• Current metal embedded in the skull
• Presence of skin lesions, open wounds, or bruising at stimulation sites; or
• Contraindications to varenicline use (e.g. pregnant/breastfeeding, alcohol dependence, kidney disease/renal impairment, known hypersensitivity to varenicline)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental Group (Active tDCS plus Varenicline)	Active Transcranial Direct Current Stimulation (tDCS)	The experimental group will receive active tDCS sessions plus 12 weeks of 1 mg varenicline bid. Participants will start varenicline treatment on the same day as the first tDCS session, and will follow a standard dose escalation schedule. The tDCS treatment schedule includes 10 daily sessions for the first 2 weeks (M to F), followed by 5 single bi-weekly booster sessions for the remainder of the treatment period. Participants will come in-person for two follow-up sessions to assess smoking behaviour at 6- and 12-months post-treatment.
Experimental Group (Active tDCS plus Varenicline)	Varenicline 1mg BID	The experimental group will receive active tDCS sessions plus 12 weeks of 1 mg varenicline bid. Participants will start varenicline treatment on the same day as the first tDCS session, and will follow a standard dose escalation schedule. The tDCS treatment schedule includes 10 daily sessions for the first 2 weeks (M to F), followed by 5 single bi-weekly booster sessions for the remainder of the treatment period. Participants will come in-person for two follow-up sessions to assess smoking behaviour at 6- and 12-months post-treatment.
Control Group	Varenicline 1mg BID	The control group will receive sham (fake) tDCS sessions plus 12 weeks of 1 mg varenicline bid. Participants will start varenicline treatment on the same day as the first tDCS session, and will follow a standard dose escalation schedule. The tDCS treatment schedule includes 10 daily sessions for the first 2 weeks (M to F), followed by 5 single bi-weekly booster sessions for the remainder of the treatment period. Participants will come in-person for two follow-up sessions to assess smoking behaviour at 6- and 12-months post-treatment.
Control Group	Sham Transcranial Direct Current Stimulation (tDCS)	The control group will receive sham (fake) tDCS sessions plus 12 weeks of 1 mg varenicline bid. Participants will start varenicline treatment on the same day as the first tDCS session, and will follow a standard dose escalation schedule. The tDCS treatment schedule includes 10 daily sessions for the first 2 weeks (M to F), followed by 5 single bi-weekly booster sessions for the remainder of the treatment period. Participants will come in-person for two follow-up sessions to assess smoking behaviour at 6- and 12-months post-treatment.

Primary Outcome Measures

Name	Time	Method
30-Day Continuous Abstinence at End-Of-Treatment	Week 9-12	Proportion of the sample that has been abstinent from smoking for 30 days at end of treatment (treatment weeks 9-12), verified with a negative urinary cotinine test.

Secondary Outcome Measures

Name	Time	Method
Long-term Sustained Abstinence at Follow-Up	Weeks 9-26 and Weeks 9-52	Continuous abstinence at 6-months (weeks 9 to 26) and 12-month (weeks 9 to 52) follow-up (verified with a negative urinary cotinine test).
Adverse events	Week 1-52	Adverse events will be recorded throughout the treatment and in follow-up visits.
Working Memory Scores	Week 1-52	The N-back Task will be used throughout the study to evaluate changes in working memory.
Attentional Bias	Week 1-52	Attentional bias towards smoking cues, sensation-seeking cues, and negative affect cues will be evaluated throughout the study using eye-tracking technology.
Inhibitory Control Scores	Week 1-52	Inhibitory control will be evaluated throughout the study using the Stop Signal Task and the Sustained Attention to Response Task.

Trial Locations

Locations (1)

Centre for Addiction and Mental Health; 🇨🇦 Toronto, Ontario, Canada