Gabapentin for Smoking Cessation

Study Overview
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Brief Summary
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Gabapentin is an anti-epileptic agent that has shown preliminary evidence of efficacy for improving symptoms of cocaine and alcohol withdrawal in pilot studies. Since the neurobiology of alcohol, cocaine and nicotine withdrawal is similar, the preliminary evidence of efficacy of gabapentin for symptoms of alcohol and cocaine withdrawal suggests, that gabapentin might likely help nicotine withdrawal symptoms and thus tobacco abstinence. The effect of gabapentin on two of the neurotransmitters, gamma-aminobutyric acid (GABA) and glutamate further suggest a potential therapeutic mechanism for gabapentin in tobacco abstinence. However, the exact mechanism of action of gabapentin is currently not known. We have recently completed an open label pilot trial of gabapentin for tobacco abstinence involving 50 smokers. The findings from that study provide promising preliminary results and suggest that further testing of gabapentin for helping cigarette smokers quit tobacco use is worth pursuing. Overall, gabapentin is well tolerated and has low abuse potential. Our goal is to evaluate novel, safe, acceptable, and effective therapies that may help increase tobacco abstinence rates. Currently, no randomized trials testing the efficacy of gabapentin for smoking abstinence have been published. While our previous study provides promising evidence regarding the potential efficacy of gabapentin for smoking abstinence, an additional dose ranging study is needed prior to pursuing a large randomized trial. The primary aim of the dose ranging study will be to obtain additional evidence of efficacy, and information on the optimal dose of gabapentin to employ in the larger randomized controlled trial.

Detailed Description
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A total of 120 participants will be recruited in this study and randomly assigned to one of the three groups. Participants in group A will receive gabapentin 1800-mg/day orally for 12-weeks while participants in group B will receive gabapentin 2700-mg/day orally for 12-weeks. Participants in group C will receive a matching placebo for the same duration. We have selected this dose regimen based on our experience with using gabapentin in the pilot study. The present study is designed as a randomized, blinded, placebo-controlled, three-arm, parallel-group, dose-ranging, phase II clinical trial. In addition to receiving gabapentin or placebo, all subjects will receive a brief behavioral counseling intervention during participation in the study.

Official Title
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Gabapentin for Smoking Abstinence

Conditions
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Cigarette Smoking, Tobacco Use

Intervention / Treatment
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* Drug: Placebo
* Drug: Gabapentin - 1800 mg/day
* Drug: Gabapentin - 2700 mg/day


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are between 18 to 65 years of age Have smoked ≥10 cigarettes/day for the past 1 year or more Are willing to make a quit attempt Are able to participate fully in all aspects of the study; and Have been provided with, understand, and have signed the informed consent. Exclusion Criteria: Meet diagnostic criteria for current major depressive disorder or lifetime history of bipolar disorder or schizophrenia. Patients with mild or moderate depressive symptoms as assessed by the CES-D and determined by the physician, but who do not meet current diagnostic criteria for major depressive disorder, will be included Are currently (within past 30 days) using antipsychotics, or antidepressants Are currently (in previous 30 days) using any tobacco treatment program (i.e., behavioral therapy, nicotine replacement therapy, bupropion SR, clonidine, or nortriptyline) Have used an investigational drug within the 30 days prior to enrolling in this study Have recent history (in the past year) of alcohol abuse or dependence as assessed by the CAGE questionnaire and study investigators Have a recent history of drug abuse as assessed by the Drug Abuse Screening Test 20 (DAST-20) and physician interview Are pregnant, lactating, or of child bearing potential, likely to become pregnant during the medication phase and not willing to use contraception. The following birth control measures are acceptable: birth control pills, approved intra-uterine contraceptive devices, the use of two combined barrier methods (diaphragm with spermicide or condom with spermicide), injections, surgical sterilization and abstinence Have a history of any major cardio-vascular events in the past 6 months including unstable angina, acute MI or coronary angioplasty Have clinically significant acute or chronic progressive or unstable neurologic (myasthenia gravis), hepatic, renal, cardiovascular, respiratory (bronchospastic disease) or metabolic disease Are currently on the following prescribed medications known to interact with gabapentin and unable to stop them during the study: Maalox®, cimetidine and morphine. Patients will be cautioned not to use sedatives (such as benzodiazepines, antihistamines, anti-cholinergics, trazodone, zaleplon, anti-psychotics, barbiturates, opiates, zolpidem and eszopiclone) during the study Have another house-hold member or relative participating in the study Have known allergy to gabapentin or its constituents; and Are professional drivers or operators of heavy machinery and unable to refrain from these activities during the medication phase of the study.

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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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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Non active placebo pill | Drug: Placebo<br>* Placebo pill - non active sugar pill designed to look alike to the gabapentin medication<br>|
| Active Comparator: Gabapentin - 1800 mg/day<br>Gabapentin - 1800 mg/day | Drug: Gabapentin - 1800 mg/day<br>* gabapentin - 1800 mg/day for 12 weeks.<br>* Other names: gabapentin;|
| Active Comparator: Gabapentin - 2700 mg/day<br>Gabapentin - 2700 mg/day | Drug: Gabapentin - 2700 mg/day<br>* gabapentin - 2700 mg/day for 12 weeks.<br>* Other names: gabapentin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemically Confirmed 7-day Point Prevalence Abstinence From Tobacco | Point prevalence tobacco abstinence was adjudicated if the following conditions were met: (a) self-reported tobacco abstinence for the previous 7 days with a negative response to the question Have you used any type of tobacco, even a puff, in the past 7 days? and (b) Expired Carbon Monoxide equal or less then 8 parts per million. | 12 weeks following start of medication | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tobacco, smoking, gabapentin, abstinence