NCT06798324

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. 1.Does active tDCS plus varenicline improve short-term and long-term smoking abstinence rates compared to sham tDCS plus varenicline?
  2. 2.Are the safety profiles between active tDCS plus varenicline and sham tDCS plus varenicline different?

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
160

participants targeted

Target at P50-P75 for phase_4

Timeline
27mo left

Started Mar 2025

Typical duration for phase_4

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress34%
Mar 2025Aug 2028

First Submitted

Initial submission to the registry

January 8, 2025

Completed
21 days until next milestone

First Posted

Study publicly available on registry

January 29, 2025

Completed
1 month until next milestone

Study Start

First participant enrolled

March 10, 2025

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 20, 2028

Expected
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2028

Last Updated

August 12, 2025

Status Verified

August 1, 2025

Enrollment Period

2.9 years

First QC Date

January 8, 2025

Last Update Submit

August 7, 2025

Conditions

Keywords

SmokingTobacco Use DisorderSmoking CessationSubstance Use DisordersBrain StimulationTranscranial Direct Current StimulationTobacco CigarettestDCSVarenicline

Outcome Measures

Primary Outcomes (1)

  • 30-Day Continuous Abstinence at End-Of-Treatment

    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.

    Week 9-12

Secondary Outcomes (5)

  • Long-term Sustained Abstinence at Follow-Up

    Weeks 9-26 and Weeks 9-52

  • Adverse events

    Week 1-52

  • Working Memory Scores

    Week 1-52

  • Attentional Bias

    Week 1-52

  • Inhibitory Control Scores

    Week 1-52

Study Arms (2)

Experimental Group (Active tDCS plus Varenicline)

ACTIVE COMPARATOR

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.

Device: Active Transcranial Direct Current Stimulation (tDCS)Drug: Varenicline 1mg BID

Control Group

SHAM COMPARATOR

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.

Drug: Varenicline 1mg BIDDevice: Sham Transcranial Direct Current Stimulation (tDCS)

Interventions

Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation. Active tDCS involves brief (e.g., 20-min) application of weak electric current (e.g., 2 mA) to the scalp. The tDCS device that will be used for this study is the Soterix 1x1 mini-CT.

Experimental Group (Active tDCS plus Varenicline)

Varenicline is the most effective approved treatment for quitting smoking. Varenicline as per standard prescribing for dose escalation (i.e. Days 1 to 3: 0.5 mg once daily; Days 4 to 7: 0.5 mg twice daily; Days 8 to end of treatment: 1 mg twice daily) will be given concurrently over the same 2 weeks as the tDCS protocol and continue for an additional 10 weeks as per standard treatment duration recommended on the product monograph for a total of 12 weeks of varenicline treatment. Dose adjustments due to adverse events will be allowed (i.e. decrease to 0.5 mg twice daily). The target quit date for smoking cessation will be on the last day of the two weeks of daily tDCS which corresponds to the recommended quit date after starting varenicline treatment.

Also known as: Champix, Chantix
Control GroupExperimental Group (Active tDCS plus Varenicline)

Sham tDCS consists of 30s of 2 mA at the beginning and at the end of the 6 session (ramp up and down), then receiving 0 mA stimulation for the middle 19 min. The tDCS device that will be used for this study is the Soterix 1x1 mini-CT.

Control Group

Eligibility Criteria

Age18 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M5T 1P7, Canada

RECRUITING

Related Publications (2)

  • Zawertailo L, Zhang H, Rahmani N, Rajji TK, Selby P. 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. PLoS One. 2022 Dec 8;17(12):e0277408. doi: 10.1371/journal.pone.0277408. eCollection 2022.

    PMID: 36480510BACKGROUND
  • Zhang H, Rajji TK, Selby P, Melamed O, Attwells S, Zawertailo L. Augmenting varenicline treatment with transcranial direct current stimulation (tDCS) increases smoking abstinence rates at end of treatment. Brain Stimul. 2023 Jul-Aug;16(4):1083-1085. doi: 10.1016/j.brs.2023.07.001. Epub 2023 Jul 3. No abstract available.

    PMID: 37406928BACKGROUND

MeSH Terms

Conditions

Tobacco Use DisorderTobacco SmokingSmoking CessationSubstance-Related DisordersSmoking

Interventions

VareniclineBID protein, human

Condition Hierarchy (Ancestors)

Chemically-Induced DisordersMental DisordersBehaviorTobacco UseHealth Behavior

Intervention Hierarchy (Ancestors)

BenzazepinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsQuinoxalines

Study Officials

  • Laurie A Zawertailo, PhD

    Centre for Addiction and Mental Health

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Laurie A Zawertailo, PhD

CONTACT

Kameron Iturralde, BSc

CONTACT

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

January 8, 2025

First Posted

January 29, 2025

Study Start

March 10, 2025

Primary Completion (Estimated)

January 20, 2028

Study Completion (Estimated)

August 1, 2028

Last Updated

August 12, 2025

Record last verified: 2025-08

Locations