Molecular Mechanisms of Pharmacological Action, Physiological Effects of Drugs, Smoking Cessation, Substance Use Disorders, Tobacco Dependence, Tobacco Smoking, Tobacco Use Disorder
Conditions
Keywords
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
Brief summary
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
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.
Interventions
DRUGVarenicline
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).
DEVICEActive tDCS
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
DEVICESham tDCS
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.
Sponsors
Centre for Addiction and Mental Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-Blind
Intervention model description
Sham Controlled Randomized Trial
Eligibility
Sex/Gender
ALL
Age
19 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in smoking status over time | At weeks 12 and 26 following start of treatment | 30 Day Continuous abstinence confirmed by expired CO \</= 4 ppm |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in functional brain activation during cognitive tasks | At baseline and 12 weeks following start of treatment | change in fMRI BOLD response in the brain in response to smoking cues or when anticipating a monetary reward |
| Change in preference of attention towards visual cues | At weeks 4,8, 12 and 26 weeks following start of treatment. | Attentional bias to smoking cues, negative/positive cues and high-risk cues measured using an automated eye-tracking apparatus |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in brain neurocircuitry over time | At baseline and 12 weeks following start of treatment | Differences in water diffusion in the brain when participants are at rest in a MRI scanner. |
| Change in dynamic functional connectivity of the brain at rest over time | At baseline and 12 weeks following start of treatment | Related to differences in resting state functional brain networks when participants are not doing an explicit task in a fMRI scanner. |
Countries
Canada
Outcome results
None listed