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

NCT00722124 | Completed Phase 2 Results

• 2 other identifiers: 07-00636507-006604
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Tobacco Dependence

Keywords

tobacco use; cigarettes; smokers

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (3)

SAMe 800

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

Drug: S-Adenosyl-L-Methionine

SAMe 1600

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

Each subject randomized to this arm will take 2 placebo pills in the AM and again in the PM

Other: placebo

Interventions

S-Adenosyl-L-Methionine DRUG

800 mg dose per day for 8 weeks

Also known as: SAMe

SAMe 800

placebo OTHER

4 pills (2 in the AM and 2 in the PM) of placebos for 8 weeks

Also known as: sugar pill

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mayo Clinic: lead
• Pharmavite LLC: collaborator

Study Sites (2)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Franciscan Skemp HealthCare

La Crosse, Wisconsin, 54601, United States

Location

Related Publications (1)

• Hajizadeh A, Howes S, Theodoulou A, Klemperer E, Hartmann-Boyce J, Livingstone-Banks J, Lindson N. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2023 May 24;5(5):CD000031. doi: 10.1002/14651858.CD000031.pub6.

  PMID: 37230961 DERIVED

MeSH Terms

Conditions

Tobacco Use Disorder; Tobacco Use

Interventions

S-Adenosylmethionine; Sugars

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Behavior

Intervention Hierarchy (Ancestors)

Methionine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Amino Acids; Amino Acids, Peptides, and Proteins; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Carbohydrates

Results Point of Contact

• Title: Amit Sood, MD
• Organization: Mayo Clinic

nicotineresearch@mayo.edu

507-266-1944

Study Officials

• Amit Sood, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 23, 2008
• First Posted: July 25, 2008
• Study Start: September 1, 2008
• Primary Completion: December 1, 2009
• Study Completion: June 1, 2010
• Last Updated: September 9, 2011
• Results First Posted: September 9, 2011

Record last verified: 2011-08

Locations

US (2)