Deep rTMS and Varenicline for Smoking Cessation

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effect of deep repetitive transcranial magnetic stimulation (rTMS) using the insula H-coil on smoking outcomes in smokers receiving varenicline. It is hypothesized that active deep rTMS will improve abstinence rates, attenuate craving and reduce cigarette consumption and dependence severity.

Detailed Description
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This study will be a randomized, double-blind, sham-controlled clinical trial. Nicotine dependent participants will be recruited and randomized tor receive either active or sham rTMS intervention for 4 weeks (5 sessions/week). All participants will receive an open-label treatment of varenicline for 12 weeks and weekly counselling sessions. The aims of the study are: To examine the efficacy of bilateral deep rTMS to the insula on point prevalence smoking abstinence in smokers receiving varenicline treatment. To examine the efficacy of bilateral deep rTMS to the insula on other smoking outcomes such as craving, cigarette smoking and dependence severity. To examine the effect of bilateral deep rTMS to the insula on abstinence at the end of rTMS treatment and at 6-month follow up. Abstinence will be measured by point prevalence at week 4 and 12 and prolonged continuous abstinence at week 26. This will be confirmed using plasma cotinine levels. All other measures will be done using various questionnaires such as Fagerstrom Test of Nicotine Dependence (FTND), Timeline Follow-Back (TLFB), Minnesota Nicotine Withdrawal Scale (MNWS), and Tiffany Questionnaire of Smoking Urges (T-QSU).

Official Title
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Deep rTMS and Varenicline for Smoking Cessation: A Pilot Study Exploring the Efficacy of a Combined Treatment Approach

Conditions
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Tobacco Use Disorder, Smoking Cessation

Intervention / Treatment
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* Device: Deep Repetitive Transcranial Magnetic Stimulation (Active)
* Device: Deep Repetitive Transcranial Magnetic Stimulation (Sham)
* Drug: Varenicline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65; Nicotine dependent as assessed by Diagnostic and Statistical Manual of Mental Disorders (DSM-V); Reported daily cigarette consumption ≥ 10 and expired carbon monoxide (CO) measurement of ≥ 10 ppm; Fagerstrom Test of Nicotine Dependence (FTND) ≥ 4; Reported motivation to quit within 30 days as assessed using the Contemplation Ladder score of ≥ 7. Exclusion Criteria: Reported smoking abstinence in the 3 months preceding screening visit; Current use of other smoking cessation aids; Allergy and/or contraindication to varenicline or rTMS; Pregnancy, trying to become pregnant or breastfeeding; Current or recent history of cardiovascular or cerebrovascular disease and/or current hypertension; Current or historical evidence of suicidal behavior; Serious current or personal history of medical condition/disease (neurological disorders, brain lesions, multiple sclerosis, head trauma, loss of consciousness, hearing loss, etc.); Current, personal history or family history of seizures; Cognitive impairment as defined as a Mini Mental State Examination (MMSE) score <24; Concomitant use of medication that lowers seizure threshold

Ages Eligible for Study
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Minimum Age: 18 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Deep rTMS active + Varenicline<br>Participants undergoing deep rTMS (active) for 4 weeks (5 sessions/week) along with 12 weeks of varenicline. | Device: Deep Repetitive Transcranial Magnetic Stimulation (Active)<br>* Active deep rTMS (10 Hz) using the H-coil to target the bilateral insula<br>Drug: Varenicline<br>* 12 week course treatment of varenicline (0.5 mg/1 mg) using the standard dosage schedule for smoking cessation (Day 1-3: 0.5 mg daily; day 4-7: 0.5 mg twice a day; day 8-end of treatment: 1 mg twice a day).<br>* Other names: Champix;|
| Sham Comparator: Deep rTMS sham + Varenicline<br>Participants undergoing deep rTMS (sham) for 4 weeks (5 sessions/week) along with 12 weeks of varenicline. | Device: Deep Repetitive Transcranial Magnetic Stimulation (Sham)<br>* Sham deep rTMS using the H-coil. The sham coil is built into the same helmet as the active coil. It mimics the active coil with regards to acoustics and scalp sensations.<br>Drug: Varenicline<br>* 12 week course treatment of varenicline (0.5 mg/1 mg) using the standard dosage schedule for smoking cessation (Day 1-3: 0.5 mg daily; day 4-7: 0.5 mg twice a day; day 8-end of treatment: 1 mg twice a day).<br>* Other names: Champix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Point prevalence abstinence at the end of 12 weeks | Measured by self-report of smoking abstinence in the past 7 days and confirmed using plasma cotinine measurement. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fagerstrom Test For Nicotine Dependence (FTND) score | This will be used to assess physical dependence severity in participants. It is a 6 item scale and total scores can range from 0-10. A higher score indicates more severe nicotine dependence. | 26 weeks | 
| Expired CO Measurements | This will be used as a biological confirmation of recent smoking. | 26 weeks | 
| Cigarettes per day (TLFB) | Self-reported measure of cigarette consumption. | 26 weeks | 
| Minnesota Nicotine Withdrawal Scale (MNWS) score | This will be used to assess withdrawal symptoms. It is an 8 item scale and total scores range from 0 to 24. A higher score indicates more severe nicotine withdrawal. | 26 weeks | 
| Tiffany Questionnaire for Smoking Urges (T-QSU) score | This will be used to assess symptoms of craving/urges for tobacco. It is a 32 item scale and total scores range from 0 to 224. A higher score indicates more severe smoking craving/urges. | 26 weeks | 
| Point prevalence abstinence at the end of 4 weeks | Measured by self-report of smoking abstinence in the past 7 days and confirmed using plasma cotinine measurement. | 4 weeks | 
| Prolonged abstinence from end of treatment (Week 12) to end of follow up (Week 26) | Measured by self-report of smoking abstinence since the last visit and confirmed using plasma cotinine measurement. | 26 weeks | 
| Prolonged abstinence with 2-week grace period at end of follow up (Week 26) | Measured by self-report of smoking abstinence since the last visit and confirmed using plasma cotinine measurement. | 26 weeks | 
| Continuous abstinence at 6 months | Measured by self-report of smoking abstinence since the last visit and confirmed using plasma cotinine measurement. | 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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smoking cessation, varenicline, deep rTMS, insula, addiction, tobacco use disorder