S-Adenosyl-L-Methionine (SAMe) for Smoking Abstinence

Study Overview
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Brief Summary
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Cigarette smoking is of great public health importance and is the single most important preventable cause of morbidity, mortality and excess health care costs in the United States. After a steady decline for the last 50 years, the prevalence of tobacco use in the United States has reached a plateau of approximately 21%. Currently available treatments among adults are not efficacious for all tobacco users. New pharmacologic agents thus need to be continually developed and tested. The release of dopamine in the nucleus accumbens is one of the key components of the pleasurable and rewarding effects of nicotine. Drugs that increase monoamine neurotransmitter availability (particularly dopamine and norepinephrine) are likely to increase the reward function and thus ameliorate withdrawal symptoms. S-Adenosyl-L-Methionine (SAMe), the primary methyl donor for the central nervous system (CNS), donates methyl groups towards presynaptic synthesis of CNS monoamine neurotransmitters. By facilitating the synthesis of dopamine and norepinephrine in the brain, SAMe is likely to ameliorate the symptoms of nicotine withdrawal, thus improving tobacco abstinence rates in smokers who are trying to stop smoking. SAMe is well tolerated and is available over-the-counter. To date, no prospective clinical trial evaluating the efficacy of SAMe for the treatment of tobacco dependence has been published. We propose to evaluate the efficacy of SAMe for increasing smoking abstinence and decreasing nicotine withdrawal symptoms in a randomized, blinded, placebo-controlled, three-arm, parallel-group, dose-ranging phase II clinical trial. Participants (N=120) will be randomly assigned to one of the three groups, and will receive an 8-week course of SAMe 800-mg per day, 1600-mg per day, or a matching placebo. This study is anticipated to provide the data needed to develop a larger randomized controlled clinical trial submitted through the R01 funding mechanism, if the results appear promising.

Detailed Description
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In this study, after consenting, subject is screened for study eligibility. If they pass the study screen, they are randomized to study drug (800 mg/day of SAMe, 1600 mg/day of SAMe or placebo-look-alike). Subjects will stay on their assigned dose for 8 weeks with weekly (visits 3-6) or biweekly (visits 7-8) clinic visits. After the 8 weeks of medication, they will receive a phone visit at week 16 and then a final visit at week 24. Study participation ends at the week 24 visit. During study participation, subjects will undergo counseling at every study visit based on the counseling manual, Smoke Free and Living It. They will also keep diaries (record of daily withdraw symptoms and tobacco use) for the 8 weeks while on study medication. At each study visit, smoking and safety outcomes are measured.

Official Title
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S-Adenosyl-L-Methionine (SAMe) for Smoking Abstinence

Conditions
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Tobacco Dependence

Intervention / Treatment
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* Drug: S-Adenosyl-L-Methionine
* Drug: S-Adenosyl-L-Methionine
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is at least 18 years of age; Has smoked more than 10 cigarettes/day for ≥6 months; Is willing to make a quit attempt; Is able to participate fully in all aspects of the study; Has been provided with, understand, and have signed the informed consent. Is in good health as determined by the physician investigator. Exclusion Criteria: Is clinically significant levels of current depression as assessed by CESD (Score >16) and determined by the physician; or have a life-time diagnosis of bipolar disorder, schizophrenia or dementia as determined by physician investigator; Has an unstable medical condition. Is using other tobacco product and the primary use is NOT cigarettes. Is currently (within the past 30-days) using antipsychotics or antidepressants; Is currently (within the past 30-days) using any treatments for tobacco dependence (i.e., behavioral therapy, nicotine replacement therapy, bupropion SR, clonidine, or nortriptyline); Is currently using another investigational drug at the time of study enrollment; Is currently (within the past 30 days) using an herbal product or dietary supplement for tobacco abstinence; Has recent history (in the past 3-months) of alcohol abuse or dependence as assessed by the CAGE questionnaire and study investigators; Has a recent history of drug abuse as assessed by physician interview; Is pregnant, lactating, or of child bearing potential, likely to become pregnant during the medication phase and not willing to use a reliable form of contraception. Reliable forms of contraception include diaphragm or condom (with spermicidal), injections, intrauterine device [IUD], surgical sterilization and abstinence; Is a history of any major cardiovascular events in the past 3-months including unstable angina, acute MI or coronary angioplasty; Has clinically significant acute or chronic progressive or unstable neurologic, hepatic, renal, cardiovascular, respiratory or metabolic disease; Is currently on medications interacting with SAMe, including but not limited to, antidepressants, MAO inhibitors, levodopa, meperidine, dextromethorphan, pentazocine and tramadol; Has another household member or relative participating in the study; Has known allergy to SAMe.

Ages Eligible for Study
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Minimum Age: 18 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: SAMe 800<br>Each subject randomized to this arm will take a 400 mg pill of SAMe and one matching placebo pill in the AM and again in the PM | Drug: S-Adenosyl-L-Methionine<br>* 800 mg dose per day for 8 weeks<br>* Other names: SAMe;|
| Active Comparator: SAMe 1600<br>Each person randomized to this arm will take 2 400 mg pills of SAMe in the AM and again in the PM | Drug: S-Adenosyl-L-Methionine<br>* 1600 mg per day for 8 weeks<br>* Other names: SAMe;|
| Placebo Comparator: Placebo<br>Each subject randomized to this arm will take 2 placebo pills in the AM and again in the PM | Other: placebo<br>* 4 pills (2 in the AM and 2 in the PM) of placebos for 8 weeks<br>* Other names: sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 7-day Point Prevalence Smoking Abstinence at End of Treatment (Week 8) | 7-day point prevalence smoking abstinence biochemically confirmed (expired carbon monoxide <8ppm) | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tobacco use, cigarettes, smokers