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

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

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.

Study Overview

• Status: Completed
• Conditions: Smoking Cessation; Tobacco Smoking; Tobacco Use Disorder; Substance Use Disorders; Molecular Mechanisms of Pharmacological Action; Tobacco Dependence; Physiological Effects of Drugs
• Intervention / Treatment: Drug: Varenicline; Device: Active tDCS; Device: Sham tDCS

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.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T1P7
      • Centre for Addiction and Mental Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Active tDCS+Varenicline; 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; 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).; Other Names: Champix; Device: Active 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
SHAM_COMPARATOR: Sham tDCS+Varenicline; 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; 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).; Other Names: Champix; Device: Sham 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.

What is the study measuring?

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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in brain neurocircuitry over time	Differences in water diffusion in the brain when participants are at rest in a MRI scanner.	At baseline and 12 weeks following start of treatment
Change in dynamic functional connectivity of the brain at rest over time	Related to differences in resting state functional brain networks when participants are not doing an explicit task in a fMRI scanner.	At baseline and 12 weeks following start of treatment

Collaborators and Investigators

• Sponsor: Centre for Addiction and Mental Health

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2018
• Primary Completion (ACTUAL): January 31, 2022
• Study Completion (ACTUAL): January 31, 2022

Study Registration Dates

• First Submitted: January 8, 2019
• First Submitted That Met QC Criteria: February 12, 2019
• First Posted (ACTUAL): February 15, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 15, 2022
• Last Update Submitted That Met QC Criteria: March 14, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Transcranial Direct Current Stimulation; Dependence; fMRI; Diffusion Tensor Imaging; Addiction; Neuroimaging; Cigarettes; Varenicline; Quitting Smoking; Eye-tracking; Attentional Bias; Tobacco Treatment; Smoking Cessation Medication; Smoking Treatment; Biochemical Confirmation; Cue reactivity; Reward Anticipation; Resting State Functional Connectivity; BOLD fMRI; Quantitative T1
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Substance-Related Disorders; Disease; Tobacco Use Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Nicotinic Agonists; Cholinergic Agonists; Varenicline
• Other Study ID Numbers: REB #044/2016

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No