Testing Methylphenidate for Smoking Abstinence

Study Overview
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Brief Summary
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Cigarette smoking continues to be a major public health problem. Tobacco dependence interventions, as recommended by the USPHS Clinical Practice Guideline are not effective for all smokers. A need exists for new medications to treat various aspects of tobacco dependence, such as the reinforcing effects of nicotine, relief of nicotine withdrawal symptoms and prevention of early relapse. The neurobiology of the effect of methylphenidate is similar to that of the reinforcing effects of nicotine. In a small previous study, methylphenidate was reported to improve nicotine withdrawal symptoms and short term quit rates. Methylphenidate is well tolerated, has low abuse potential, and is less expensive compared to other tobacco dependence interventions. ConcertaTM, a long acting preparation of methylphenidate, is administered once a day, has similar bioavailability as the generic drug administered 3 times a day and has an overall similar or improved efficacy compared to generic methylphenidate. We plan to obtain preliminary efficacy data in a randomized, placebo-controlled phase II study assessing the effect of methylphenidate in cigarette smokers for increasing 7-day point prevalence smoking abstinence at end of treatment and 7-day point prevalence and prolonged smoking abstinence at 6-months. Critical and systematic evaluations of newer, innovative, and well-tolerated treatments to help treat tobacco use and dependence will provide a wider choice of therapeutic agents to smokers wishing to become abstinent from tobacco use.

Detailed Description
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Once enrolled in study, the subject will be put in one of 2 groups by chance (as in the flip of a coin). They will either receive methylphenidate or a placebo. Everyone in study will receive nicotine dependence counseling based on the intervention manual Smoke Free and Living It. Everyone will be asked to complete weekly study visits for 8 weeks and one follow-up phone call at week 16 and a final study visit at week 24. The target quit day is the day after visit 4 (week 2 + 1 day). In the first two weeks after starting study medication they will slowly build up to 3 pills a day. For weeks 2 through 8 they will continue to take 3 pills a day.

Official Title
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Efficacy of Methylphenidate for Treating Tobacco Dependence

Conditions
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Smoking

Intervention / Treatment
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* Drug: Methylphenidate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are between 18 to 65 years of age Have smoked cigarettes daily for the past 6-months and are currently smoking > 10 cigarettes/day Are willing to make an attempt to stop smoking Are able to participate fully in all aspects of the study Have been provided with, understand, and have signed the informed consent Exclusion Criteria: Have clinically significant levels of current depression as assessed by CESD and determined by the physician; or have a life-time diagnosis of bipolar disorder, schizophrenia or dementia as determined by physician investigator Are currently (in previous 30 days) using any tobacco treatment program (i.e., behavioral therapy, nicotine replacement therapy, bupropion SR, varenicline, clonidine or nortriptyline) Have used an investigational drug within the 30 days prior to enrolling in this study Alcohol or drug abuse or dependence within the past year as assessed by the study investigators using CAGE questionnaire and the Drug Abuse Screening Test 20 (DAST-20) Are pregnant, lactating, or of child bearing potential, likely to become pregnant during the medication phase and not willing to use contraception. The following birth control measures are acceptable: approved hormonal contraceptive medications or devices, approved intra-uterine contraceptive devices, the use of two combined barrier methods (diaphragm with spermicide or condom with spermicide), birth control pills, injections, intrauterine device [IUD], abstinence, or surgical sterilization of subject or of monogamous partner. Have a history of any major cardiovascular event in the past 6-months including unstable angina, acute MI or coronary angioplasty Have clinically significant acute or chronic, progressive or unstable neurologic (dementia, delirium or seizure disorder), hepatic, renal, cardiovascular, respiratory or metabolic disease that would limit participation in the study Are currently on the following prescribed medications known to interact with methylphenidate and not able to stop the medication during the study period: stimulants, warfarin, anticonvulsants, antidepressants, antipsychotics, monoamine oxidase inhibitors, clonidine, theophylline and pseudo-ephedrine Uncontrolled hypertension (>160/100) or tachycardia (Heart rate >110) Have another house-hold member or relative participating in the study Have known allergy to methylphenidate or its constituents Have a specific medical condition where use of methylphenidate is contraindicated: narrow angle glaucoma, motor tics, family history or diagnosis of Tourette's syndrome, and history of GI obstruction (including history of strictures, adhesions, or abdominal surgery) have an ECG with significant arrhythmias or abnormal conduction, which in the opinion of the physician investigator preclude participating in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Methylphenidate<br>54 mg Methylphenidate per day for 8 weeks. Allowing for a ramp up in the first two weeks (starting dose is 18 mg/day). | Drug: Methylphenidate<br>* 54 mg Methylphenidate per day for 8 weeks. Allowing for a ramp up in the first two weeks (starting dose is 18 mg/day).<br>* Other names: Methylphenidate, Osmotic Release methylphenidate (OROS-MPH);|
| Placebo Comparator: Placebo<br>non-active (sugar pill)designed to be a look-alike to the methylphenidate. Given at the same frequency and dosage look-alike to the active comparator (methylphenidate 54 mg) | Drug: Placebo<br>* non-active (sugar pill)designed to be a look-alike to the methylphenidate. Given at the same frequency and dosage look-alike to the active comparator (methylphenidate 54 mg)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Biochemically Confirmed to be Abstinent From Smoking at End of Treatment. | Number of subject who self report no smoking in the last 7 days (7-day point prevalence)at the end of the medication phase (week 8) and are biochemically confirmed (expired carbon monoxide <= 8 ppm) | 8 weeks | 
| Number of Subjects Biochemically Confirmed to be Abstinent From Smoking at End of Study | Number of subject who self report no smoking in the last 7 days (7-day point prevalence)at the end of study (week 24) and are biochemically confirmed (expired carbon monoxide <= 8 ppm) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Change in the Average Nicotine Withdrawal Symptom Score From Baseline to 14 Days Post Target Quit Date. | The average composite nicotine withdrawal score (using Minnesota Nicotine Withdrawal Scale) change from baseline for the first 14 days following target quit date. Scale scores range from 0 (none) to 4 (severe). | baseline and 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nicotine dependence, tobacco dependence