Using Non-invasive Brain Stimulation (tDCS) With Varenicline for Treating Tobacco Dependence

Study Overview
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Brief Summary
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The addition of tDCS as an adjunct to pharmacotherapy is a novel approach but one that is grounded in a growing evidence-base.The primary objective of this research is to provide preliminary evidence of the effectiveness of tDCS as an adjunct treatment to pharmacotherapy for smoking cessation. The investigators hypothesize that the addition of active tDCS to the left DLPFC will improve the effectiveness of varenicline as reflected by higher quit rates at end of treatment compared to the sham group. Smoking status will be biochemically confirmed at various time points using expired cotinine measures. Furthermore, the investigators will be collecting neuroimaging (fMRI) data as well as measures of attentional bias to explore the neurological and physiological correlates from using adjunct tDCS and varenicline therapy.

Detailed Description
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While varenicline on its own is the most effective medication for smoking cessation, long-term abstinence is still relatively poor. The primary objective of this study is to evaluate the effectiveness of adjunct active tDCS with varenicline in treating tobacco dependence. This study is a double-blind, sham-controlled, randomized clinical trial where 50 daily dependent treatment seeking smokers will be recruited at the Nicotine Dependence Clinic in Toronto, Canada. Participants will be receiving twelve weeks of varenicline treatment (1mg b.i.d.) and randomized 1:1 to either active tDCS (active: 20 minutes at 2 mA) or sham tDCS (30 seconds at 2 mA, 19.5 minutes at 0 mA), daily (M-F) for the first 2 weeks and then every 2 weeks for the next 10 weeks. There will be 2 fMRI scans at baseline and 1 scan at end-of-treatment. Eye-tracking viewing tests will be conducted at baseline, weeks 4, 8, 12 and at 6 months follow up. During the 6 month follow-up, participants will be answering questions regarding their smoking behaviour and craving. Smoking status will be biochemically confirmed at each study visit using expired cotinine.

Official Title
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Using Non-invasive Brain Stimulation (tDCS) to Improve the Effectiveness of Varenicline for Treating Tobacco Dependence: a Randomized Controlled Trial

Conditions
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Tobacco Dependence, Smoking Cessation, Tobacco Smoking, Tobacco Use Disorder, Substance Use Disorders, Molecular Mechanisms of Pharmacological Action, Physiological Effects of Drugs

Intervention / Treatment
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* Drug: Varenicline
* Device: Active tDCS
* Device: Sham tDCS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female Aged 19-65 Treatment seeking smoker Daily smoker of CPD>8 Able to attend daily appointments for tDCS for the first 2 weeks and booster sessions for the next 10 weeks. Wiling to undergo 3 fMRI sessions Exclusion Criteria: Current/recent DSM-IV Axis I diagnosis Current use of psychoactive drugs or medications History of seizures/epilepsy Current use of NRT, e-cigarettes or other medications for smoking cessation Metal embedded in skull or implanted electrical devices No head injury (concussion or loss of consciousness for more than an hour) Contraindications to fMRI Contraindications to varenicline

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Sham Controlled Randomized Trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active tDCS+Varenicline<br>Active 2mA tDCS (Nuraleve, Canada) with the anode placed over the left dorsolateral prefrontal cortex (dlPFC) and the cathode placed over the right dlPFC for 20 minutes per session. Daily stimulation between Monday to Friday for the first two weeks and then booster sessions every other week for the next 10 weeks. | Drug: Varenicline<br>* Varenicline (Champix®), Pfizer Canada Inc., Kirkland, Quebec. Dispense for 12 weeks. One tablet (0.5mg) once daily for first three days, then one tablet (0.5 mg) twice daily for next four days, then 1 mg (one 1mg tablet) twice daily for the remainder of 12 weeks. Dose adjustments due to adverse events will be allowed (i.e. decrease to 0.5 mg twice daily).<br>* Other names: Champix;Device: Active tDCS<br>* Active 2mA tDCS (Nuraleve, Canada) with the anode placed over the left dorsolateral prefrontal cortex (dlPFC) and the cathode placed over the right dlPFC for 20 minutes per session<br>|
| Sham Comparator: Sham tDCS+Varenicline<br>Sham tDCS (Nuraleve, Canada)(30 seconds of 2mA and 19.5 minutes of 0 mA) with the anode placed over the left dorsolateral prefrontal cortex (dlPFC) and the cathode placed over the right dlPFC for 20 minutes per session. Daily stimulation between Monday to Friday for the first two weeks and then booster sessions every other week for the next 10 weeks. | Drug: Varenicline<br>* Varenicline (Champix®), Pfizer Canada Inc., Kirkland, Quebec. Dispense for 12 weeks. One tablet (0.5mg) once daily for first three days, then one tablet (0.5 mg) twice daily for next four days, then 1 mg (one 1mg tablet) twice daily for the remainder of 12 weeks. Dose adjustments due to adverse events will be allowed (i.e. decrease to 0.5 mg twice daily).<br>* Other names: Champix;Device: Sham tDCS<br>* Shame tDCS (Nuraleve, Canada) (30 seconds of 2mA and 19.5 minutes of 0 mA) with the anode placed over the left dorsolateral prefrontal cortex (dlPFC) and the cathode placed over the right dlPFC for 20 minutes per session.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in smoking status over time | 30 Day Continuous abstinence confirmed by expired CO </= 4 ppm | At weeks 12 and 26 following start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in functional brain activation during cognitive tasks | change in fMRI BOLD response in the brain in response to smoking cues or when anticipating a monetary reward | At baseline and 12 weeks following start of treatment | 
| Change in preference of attention towards visual cues | Attentional bias to smoking cues, negative/positive cues and high-risk cues measured using an automated eye-tracking apparatus | At weeks 4,8, 12 and 26 weeks following start of treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Smoking Cessation Medication, Smoking Treatment, Tobacco Treatment, Quitting Smoking, Varenicline, Transcranial Direct Current Stimulation, Neuroimaging, fMRI, Attentional Bias, Eye-tracking, Dependence, Addiction, Cigarettes, Biochemical Confirmation, Cue reactivity, Reward Anticipation, Diffusion Tensor Imaging, Resting State Functional Connectivity, BOLD fMRI, Quantitative T1