tDCS + Varenicline for Smoking Cessation

Overseen By Laurie A Zawertailo, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Centre for Addiction and Mental Health

Must be taking: Varenicline

Must not be taking: Buproprion, NRT, Cytisine

Disqualifiers: Unstable psychiatric illness, Seizures, Pregnancy, Pacemakers, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 12

Duration: 12 weeks

160 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have used smoking cessation medications in the past 3 months.

What data supports the effectiveness of the treatment tDCS + Varenicline for smoking cessation?

Research suggests that transcranial direct current stimulation (tDCS) can reduce cigarette cravings, and when combined with varenicline, it may improve smoking cessation outcomes. Studies have shown that tDCS can decrease cravings by about 50% in smokers, indicating its potential as a supportive treatment for quitting smoking. ^{1 2 3 4 5}

Is the combination of tDCS and varenicline safe for smoking cessation?

Varenicline is generally well tolerated, but it can cause nausea, insomnia, and headaches. There are concerns about potential neuropsychiatric effects like mood changes and suicidal thoughts, especially in people with mental health issues. tDCS is a non-invasive brain stimulation technique, and while specific safety data for its combination with varenicline is limited, both treatments have been used safely in humans separately. ^{1 6 7 8 9}

How does the treatment tDCS + Varenicline for smoking cessation differ from other treatments?

This treatment is unique because it combines transcranial direct current stimulation (tDCS), which uses a mild electrical current to reduce cravings and withdrawal symptoms, with varenicline, a drug that targets specific brain receptors to reduce cravings and block the rewarding effects of smoking. This combination aims to enhance smoking cessation outcomes more effectively than using varenicline alone. ^{1 2 5 7 10}

Research Team

Laurie A Zawertailo, PhD

Principal Investigator

Centre for Addiction and Mental Health

Eligibility Criteria

This trial is for individuals seeking to quit smoking and are struggling with tobacco use disorder. Participants should be willing to undergo daily sessions of tDCS and take varenicline as prescribed. Specific eligibility details were not provided, so interested individuals should inquire further.

Inclusion Criteria

Is seeking treatment for tobacco dependence

Smoke ≥ 8 cigarettes per day (CPD)

Be able to provide informed written consent

Exclusion Criteria

Current regular use of nicotine-containing products besides cigarettes (e.g. electronic cigarettes, etc.)

Current pacemakers or implanted electrical devices

I have used smoking cessation aids in the last 3 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive active tDCS sessions plus 12 weeks of varenicline. The tDCS treatment includes 10 daily sessions for the first 2 weeks, followed by 5 bi-weekly booster sessions.

12 weeks

10 visits (2 in-person, 8 virtual) for initial sessions, 5 in-person booster sessions

Follow-up

Participants are monitored for smoking behavior at 6- and 12-months post-treatment.

12 months

2 visits (in-person)

Treatment Details

Interventions

• Active Transcranial Direct Current Stimulation (tDCS)
• Sham Transcranial Direct Current Stimulation (tDCS)
• Varenicline

Trial Overview The study tests if active tDCS combined with the medication varenicline helps people stop smoking better than a sham (fake) tDCS plus varenicline. It includes daily sessions for two weeks, bi-weekly boosters thereafter, and follow-ups at 6 and 12 months.

Participant Groups

Group I: Experimental Group (Active tDCS plus Varenicline) Active Control 2 Interventions

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.

Group II: Control Group Placebo Group 2 Interventions

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.

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Findings from Research

This study investigates the effectiveness of transcranial Direct Current Stimulation (tDCS) combined with varenicline for smoking cessation in a double-blind, sham-controlled trial involving 50 healthy smokers over a 12-week treatment period.

The primary goal is to determine if active tDCS can improve 30-day continuous abstinence rates compared to sham tDCS, while also using MRI scans to explore potential changes in brain structure and function related to addiction treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Zawertailo, L., Zhang, H., Rahmani, N., et al.[2023]

In a study involving 210 tobacco-dependent male participants, transcranial Direct Current Stimulation (tDCS) for 12 weeks showed a 25.7% abstinence rate, comparable to the 20% rate achieved with bupropion, suggesting tDCS could be an effective alternative for smoking cessation.

Participants receiving tDCS had lower nicotine dependency scores compared to those treated with bupropion, indicating that tDCS may not only help with quitting smoking but also reduce the level of addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of transcranial direct current stimulation compared to standard bupropion for the treatment of tobacco dependence: A randomized sham-controlled trial. Ghorbani Behnam, S., Mousavi, SA., Emamian, MH.[2020]

Transcranial direct current stimulation (tDCS) applied to the dorsolateral prefrontal cortex (DLPFC) significantly reduced cigarette craving by about 50% in a study of 20 smokers, indicating its potential as a treatment for smoking addiction.

While the number of cigarettes smoked did not change, the study suggests that tDCS may be more effective for smokers with higher nicotine dependence and motivation to quit, highlighting the need for further research in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation of the prefrontal cortex reduces cigarette craving in not motivated to quit smokers: A randomized, sham-controlled study. Perri, RL., Perrotta, D.[2021]

In a study involving 30 patients with heroin dependency, transcranial direct current stimulation (tDCS) effectively reduced the objective measure of cigarette smoking, as indicated by lower expired CO concentrations after 5 days of treatment.

Both the active tDCS and sham control groups reported a decrease in the number of cigarettes smoked, but there was no significant difference in craving levels between the two groups, suggesting that while tDCS may help reduce smoking behavior, it does not significantly impact the desire to smoke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation (tDCS) may reduce the expired CO concentration among opioid users who smoke cigarettes: a randomized sham-controlled study. Lin, SH., Chen, PS., Chen, KC., et al.[2022]

In a randomized sham-controlled trial involving 44 participants, both active and sham tDCS groups showed a significant decrease in daily cigarette consumption and craving, but there were no improvements in executive functions, indicating that the effects may not be due to the stimulation itself.

The study suggests that high perceived stress and low self-control may predict successful reductions in cigarette consumption, highlighting the potential influence of psychological factors over the effects of tDCS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The influence of perceived stress and self-control on efficacy of repeated transcranial direct current stimulation in non-treatment-seeking smokers. Müller, T., Shevchenko, Y., Gerhardt, S., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

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. [2023]

2. England pubmed.ncbi.nlm.nih.gov

The effects of transcranial direct current stimulation compared to standard bupropion for the treatment of tobacco dependence: A randomized sham-controlled trial. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation of the prefrontal cortex reduces cigarette craving in not motivated to quit smokers: A randomized, sham-controlled study. [2021]

4. Ireland pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation (tDCS) may reduce the expired CO concentration among opioid users who smoke cigarettes: a randomized sham-controlled study. [2022]

5. Ireland pubmed.ncbi.nlm.nih.gov

The influence of perceived stress and self-control on efficacy of repeated transcranial direct current stimulation in non-treatment-seeking smokers. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Varenicline: mode of action, efficacy, safety and accumulated experience salient for clinical populations. [2021]

7. Spain pubmed.ncbi.nlm.nih.gov

Varenicline: new treatment with efficacy in smoking cessation. [2017]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Preclinical Pharmacology, Efficacy and Safety of Varenicline in Smoking Cessation and Clinical Utility in High Risk Patients. [2021]

9. New Zealand pubmed.ncbi.nlm.nih.gov

A preliminary benefit-risk assessment of varenicline in smoking cessation. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Compromised neuroplasticity in cigarette smokers under nicotine withdrawal is restituted by the nicotinic α4β2-receptor partial agonist varenicline. [2018]