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.
Primary Outcome Measures:
- 7- and 30-day point prevalence and prolonged smoking abstinence rates at end of treatment (week 8) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- 7- and 30-day point prevalence and prolonged smoking abstinence rates at 6-months. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- To obtain preliminary estimates of the effect of an 8-week course of SAMe on symptoms of nicotine withdrawal [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
| Estimated Enrollment: |
150 |
| Study Start Date: |
September 2008 |
| Estimated Study Completion Date: |
December 2009 |
| Estimated Primary Completion Date: |
September 2009 (Final data collection date for primary outcome measure) |
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A: Active Comparator
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
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Drug: S-Adenosyl-L-Methionine
800 mg dose per day for 8 weeks
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B: Active Comparator
Each person randomized to this arm will take 2 400 mg pills of SAMe in the AM and again in the PM
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Drug: S-Adenosyl-L-Methionine
1600 mg per day for 8 weeks
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C: Placebo Comparator
Each subject randomized to this arm will take 2 placebo pills in the AM and again in the PM
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Other: placebo
4 pills (2 in the AM and 2 in the PM) of placebos for 8 weeks
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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.
Purpose
