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

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT00722124
• Collaborator: Pharmavite LLC (Industry)
• Enrollment: 150
• Locations: 2
• Arms: 3
• Duration (Months): 21
• Patients Per Site: 75
• Patients Per Site Per Month: 3.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Tobacco Dependence	Drug: S-Adenosyl-L-Methionine; Drug: S-Adenosyl-L-Methionine; Other: placebo	Phase 2/Phase 3

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: S-Adenosyl-L-Methionine (SAMe) for Smoking Abstinence
• Study Start Date: Sep 1, 2008
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: SAMe 800 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; 800 mg dose per day for 8 weeks; Other Names: SAMe
Active Comparator: SAMe 1600 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; 1600 mg per day for 8 weeks; Other Names: SAMe
Placebo Comparator: Placebo Each subject randomized to this arm will take 2 placebo pills in the AM and again in the PM	Other: placebo; 4 pills (2 in the AM and 2 in the PM) of placebos for 8 weeks; Other Names: sugar pill

Outcome Measures

Primary Outcome Measures

1. 7-day Point Prevalence Smoking Abstinence at End of Treatment (Week 8) [8 weeks]

   7-day point prevalence smoking abstinence biochemically confirmed (expired carbon monoxide <8ppm)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905
2	Franciscan Skemp HealthCare	La Crosse	Wisconsin	United States	54601

Sponsors and Collaborators

• Mayo Clinic
• Pharmavite LLC

Investigators

• Principal Investigator: Amit Sood, M.D., Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Mayo Clinic Clinical Trials

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00722124
• Other Study ID Numbers: 07-006365; 07-006604
• First Posted: Jul 25, 2008
• Last Update Posted: Sep 9, 2011
• Last Verified: Aug 1, 2011

• Keywords provided by , ,: tobacco use; cigarettes; smokers
• Additional relevant MeSH terms: Tobacco Use Disorder

Study Results

Participant Flow

Recruitment Details	Recruitment began on 10/07/08 and completed on 10/01/09. Interested subjects who passed a phone pre-screen were seen at a medical clinic (Mayo Clinic in Rochester, MN and Franciscan Skemp Medical Center in Lacrosse, WI) for consenting and additional study procedures to determine eligibility.

Arm/Group Title	SAMe 800	SAMe 1600	Placebo
Arm/Group Description	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	Each person randomized to this arm will take 2 400 mg pills of SAMe in the AM and again in the PM	Each subject randomized to this arm will take 2 placebo pills in the AM and again in the PM
Period Title: Overall Study
STARTED	40	40	40
COMPLETED	23	26	20
NOT COMPLETED	17	14	20

Baseline Characteristics

Arm/Group Title	SAMe 800	SAMe 1600	Placebo	Total
Arm/Group Description	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	Each person randomized to this arm will take 2 400 mg pills of SAMe in the AM and again in the PM	Each subject randomized to this arm will take 2 placebo pills in the AM and again in the PM	Total of all reporting groups
Overall Participants	40	40	40	120
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	34 85%	40 100%	38 95%	112 93.3%
>=65 years	6 15%	0 0%	2 5%	8 6.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.1 (16.0)	40.8 (12.3)	37.0 (13.6)	39.9 (14.1)
Sex: Female, Male (Count of Participants)
Female	17 42.5%	20 50%	20 50%	57 47.5%
Male	23 57.5%	20 50%	20 50%	63 52.5%
baseline smoking rate (cigarettes per day) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cigarettes per day]	19.5 (9.3)	19.9 (8.4)	19.5 (8.0)	19.6 (8.5)

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Analysis was performed using intention to treat(ITT). Subjects who discontinued study participation were assumed to be smoking.

Arm/Group Title	SAMe 800	SAMe 1600	Placebo
Arm/Group Description
Measure Participants	40	40	40
Number [participants]	7 17.5%	5 12.5%	7 17.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SAMe 800, Placebo
	Comments	Data were compared between treatment groups using Fisher's Exact test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.615
	Comments
	Method	Fisher Exact
	Comments	1 sided

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SAMe 1600, Placebo
	Comments	Data were compared between treatment groups using Fisher's Exact test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.826
	Comments
	Method	Fisher Exact
	Comments	1 sided

Adverse Events

Arm/Group Title	SAMe 800		SAMe 1600		Placebo
Arm/Group Description	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		Each person randomized to this arm will take 2 400 mg pills of SAMe in the AM and again in the PM		Each subject randomized to this arm will take 2 placebo pills in the AM and again in the PM
All Cause Mortality
	SAMe 800		SAMe 1600		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	SAMe 800		SAMe 1600		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		0/40 (0%)		0/40 (0%)
Other (Not Including Serious) Adverse Events
	SAMe 800		SAMe 1600		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/40 (17.5%)		12/40 (30%)		6/40 (15%)
Gastrointestinal disorders
abdominal pain	2/40 (5%)		5/40 (12.5%)		1/40 (2.5%)
nausea	2/40 (5%)		2/40 (5%)		2/40 (5%)
diarrhea	0/40 (0%)		3/40 (7.5%)		0/40 (0%)
constipation	1/40 (2.5%)		0/40 (0%)		0/40 (0%)
flatulence	0/40 (0%)		1/40 (2.5%)		0/40 (0%)
heartburn	0/40 (0%)		1/40 (2.5%)		0/40 (0%)
vomiting	0/40 (0%)		1/40 (2.5%)		0/40 (0%)
General disorders
headache	2/40 (5%)		0/40 (0%)		2/40 (5%)
insomnia	0/40 (0%)		1/40 (2.5%)		1/40 (2.5%)
confusion	0/40 (0%)		1/40 (2.5%)		0/40 (0%)
dizziness	0/40 (0%)		0/40 (0%)		1/40 (2.5%)
drowsiness/fatigue	1/40 (2.5%)		0/40 (0%)		0/40 (0%)
vivid dreams	0/40 (0%)		0/40 (0%)		1/40 (2.5%)
Metabolism and nutrition disorders
anorexia	0/40 (0%)		1/40 (2.5%)		0/40 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.