Trial to Evaluate the Efficacy of Simvastatin for Smoking Cessation

Study Overview
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Brief Summary
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Tobacco smoking is the number one preventable cause of disease worldwide. Unfortunately, there are few smoking cessation agents and their effectiveness has been shown to be relatively limited and is associated with potential unwanted effects. Therefore, the discovery of new medications that can facilitate abstinence and reduce relapse to cigarette use represents a pressing necessity. In the attempt to find molecules that could reduce drug-seeking behavior, we discovered that simvastatin reduces cocaine and nicotine, but not food, seeking behavior in rats. This discovery of a new therapeutic application for an already marketed class of compounds may greatly facilitate the translation from preclinical to clinical setting. In this project, we aim at investigating whether simvastatin is an effective smoking cessation agent in humans. The study design is a multicenter, randomized, double blind 2 parallel groups, clinical trial with an intention-to-treat analysis. Smokers will randomly be assigned to receive simvastatin or placebo for 3 months. 200 smokers (100 receiving simvastatin and 100 receiving placebo) will be recruited through already established networks of general practitioners. The primary outcome of the efficacy of simvastatin will be the rate of smoking abstinence during the last month of the 3-month treatment period, defined as reported continuous abstinence from smoking and confirmed by expired air carbon monoxide and urinary cotinine concentration. The last assessment will be done 6 months after the predefined quit date. The results of this proof-of-concept study may open new perspectives in the treatment of tobacco use and dependance.

Official Title
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Pilot Randomized Double Blind, Placebo Controlled Trial of the Efficacy of Simvastatin for Smoking Cessation

Conditions
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Smoking Cessation

Intervention / Treatment
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* Drug: simvastatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >=18 and <=70 years, Smoking more than 10 cigarettes per day for at least 1 year, Motivated to quit smoking, Without legal tutors or subordination, Affiliated to a health insurance system as required by the French law on biomedical research, Written informed consent for participation in the study. Exclusion Criteria: Age < 18 or > 70 years, Presenting a contraindication to simvastatin use, With depression and/or psychosis and/or cognitive disorder and/or mental retardation or chronic use of medications for these disorders, Substance use disorder other than smoking, More than 3 months of abstinence from cigarette smoking in the previous year, Use of nicotine replacement therapy, bupropion, varenicline on last 3 months, Use of clonidine or nortriptyline on last 3 months, Undergoing on last 3 months' cognitive-behavioral therapy for smoking cessation, Premenopausal women without contraception.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: simvastatin<br>oral administration, capsule of 20mg. | Drug: simvastatin<br> <br> |
| Placebo Comparator: microcrystalline cellulose<br>oral administration, capsule of 20mg | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self-reported number of cigarettes smoked |  | After 3 months of simvastatin treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self-reported continuous abstinence during the last 4 weeks of the 3 months of treatment with simvastatin versus placebo |  | After 3 months of simvastatin treatment | 
| Expired air carbon monoxide ≤ 8 ppm |  | After 3 months of simvastatin treatment | 
| Urinary cotinine concentration ≤ 10 ng/mL |  | After 3 months of simvastatin treatment | 
| Nicotine craving assessed by the FTCQ-12 |  | After 3 months of simvastatin treatment |