Baclofen for Smoking Cessation in a Non-Psychiatric Population

Study Overview
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Brief Summary
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The primary hypothesis for this study is that, in nicotine-dependent tobacco smokers, baclofen will be superior to placebo for smoking abstinence measures. The secondary hypothesis is that subjects assigned to the baclofen groups will exhibit higher rates of medication compliance (i.e. take the medication as directed for the trial period) than those in the placebo group. The tertiary hypothesis is that baclofen will lead to significant reductions in tobacco withdrawal and craving ratings as compared to placebo.

Detailed Description
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This study will test a new medication strategy designed to help smokers quit. It will evaluate Baclofen, a drug currently approved and available in Canada as a myorelaxant. Forty five nicotine-dependent smokers will enroll in this study. Fifteen will receive placebo (inactive pill), fifteen will receive baclofen 30 mg/day, and fifteen will receive baclofen 60 mg/day. Once enrolled, subjects will visit CAMH on a weekly basis for assessment of smoking behaviour, a brief health check (vitals, BP and AE screening), delivery of brief individual smoking cessation counselling, and collection of breath, blood and urine samples (as scheduled) to a) measure levels of nicotine and its metabolites, b) conduct pregnancy and tox testing. The medication phase of this study lasts 12 weeks. Two follow-up visits will be scheduled at week 13 and at six months after trial completion.

Official Title
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Testing the GABAergic Hypothesis of Nicotine Dependence: a Randomized Clinical Trial of Baclofen

Conditions
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Nicotine Dependence

Intervention / Treatment
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* Drug: Baclofen 30 mg/day
* Drug: placebo pill
* Drug: Baclofen 60 mg/day


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female adults (18 years or older). Meet DSM-IV criteria for nicotine dependence, Smoke ≥10 cigarettes/day, Baseline FTND score ≥4, CO level ≥10, have had at least one failed quit attempt in the past and are motivated to quit within 30 days of initial intake. No previous use of medication for smoking cessation in 1 month prior to randomization. BMI between 15 and 40 inclusive. Exclusion Criteria: Meet DSM-IV criteria for a current diagnosis of major depressive disorder, panic disorder or post-traumatic stress disorder, or a current or past history of bipolar disorder or schizophrenia Have a past history of major depression, with historical evidence of suicidal or homicidal behaviour, or psychotic symptom, Have abused alcohol or other drugs of abuse (cocaine, opiates, benzodiazepines, etc) in 3 months prior to randomization Demonstrate serious medical conditions, unstable cardiovascular disease, significant blood abnormalities) Are pregnant, are trying to become pregnant or are currently breastfeeding Baclofen hypersensitivity .

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Baclofen 30 mg/day<br>Baclofen medication | Drug: Baclofen 30 mg/day<br>* Baclofen 30 mg/day for 8 weeks with 2 week induction and 2 week decrease<br>* Other names: Lioresal, Kemstro;|
| Placebo Comparator: Placebo pill<br>placebo pill | Drug: placebo pill<br>* placebo pill<br>|
| Active Comparator: Baclofen 60 mg/day<br>Baclofen medication high dose | Drug: Baclofen 60 mg/day<br>* baclofen 60 mg/day for 8 weeks with 2 week induction and 2 week decrease<br>* Other names: Lioresal, Kemstro;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Smoking abstinence for 7 days at end of treatment | At end of treatment subjects will report smoking consumption for past 7 days. Subject are considered abstinent based on self report and verfied by CO level (<10 PPM) | end of treatment week 10 | 
| Abstinent rate: last four weeks of trial | subjects report cigarette consumption during the last 4 weeks of the clinical trial. abstinence rates are verifed by CO < 10 PPM | last 4 weeks of trial (week 7 to 10) | 
| abstinence rate: for past 7 days at 6 month followup | Subject are asked to attend a 6 month followup. At this time subjects will be asked to report their cigarette consumption for the past 7 days. abstinence is based on this self report and verified by CO levels <10 PPM | 6 month followup | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tiffany Questionnaire of Smoking Urges | tobacco craving is monitored at different time points of the trial | screen, week 1,4,7,10, abd 6 month followup | 
| Minnesota Nicotine Withdrawal Scale | This scale assesses symptoms of tobacco withdrawal including nicotine craving, irritability, anziety, difficulty conentrating, restlessness, headaches, fatigue, increased appetite, weight gain, and insomnia. | Screen, week 1,4,7,10 and 6 month followup | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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smoking cessation treatment, baclofen, Smoking cessation counselling