Smoking
Conditions
Keywords
nicotine dependence, tobacco dependence
Brief summary
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
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.
Interventions
DRUGMethylphenidate
54 mg Methylphenidate per day for 8 weeks. Allowing for a ramp up in the first two weeks (starting dose is 18 mg/day).
DRUGPlacebo
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)
Sponsors
Ortho-McNeil Janssen Scientific Affairs, LLC
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Are between 18 to 65 years of age 2. Have smoked cigarettes daily for the past 6-months and are currently smoking \> 10 cigarettes/day 3. Are willing to make an attempt to stop smoking 4. Are able to participate fully in all aspects of the study 5. Have been provided with, understand, and have signed the informed consent
Exclusion criteria
1. 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 2. Are currently (in previous 30 days) using any tobacco treatment program (i.e., behavioral therapy, nicotine replacement therapy, bupropion SR, varenicline, clonidine or nortriptyline) 3. Have used an investigational drug within the 30 days prior to enrolling in this study 4. 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) 5. 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. 6. Have a history of any major cardiovascular event in the past 6-months including unstable angina, acute MI or coronary angioplasty 7. 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 8. 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 9. Uncontrolled hypertension (\>160/100) or tachycardia (Heart rate \>110) 10. Have another house-hold member or relative participating in the study 11. Have known allergy to methylphenidate or its constituents 12. 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) 13. have an ECG with significant arrhythmias or abnormal conduction, which in the opinion of the physician investigator preclude participating in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Biochemically Confirmed to be Abstinent From Smoking at End of Treatment. | 8 weeks | 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) |
| Number of Subjects Biochemically Confirmed to be Abstinent From Smoking at End of Study | 6 months | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Change in the Average Nicotine Withdrawal Symptom Score From Baseline to 14 Days Post Target Quit Date. | baseline and 14 days | 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). |
Countries
United States
Participant flow
Recruitment details
Recruitment for this study began on 03/10/08 and the final subject was randomized to study drug on 11/4/08. All subjects were recruited at Mayo Clinic in Rochester, MN.
Pre-assignment details
After obtaining consent, subjects were screened for study inclusion. If they passed study entry criteria, they were randomized to study. All randomized subjects were included in the analysis.
Participants by arm
| Arm | Count |
|---|---|
| Methylphenidate osmotic-release methylphenidate (OROS-MPH) at a dose of one 18 mg tablet a day with a dose escalation schedule in the first 2 weeks to achieve a maximum dose of 54 mg (three 18 mg tablets once daily) | 40 |
| Placebo Look alike placebo pill with same dosing schedule as active methylphenidate | 40 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 0 |
| Overall Study | Lost to Follow-up | 7 | 4 |
| Overall Study | Withdrawal by Subject | 6 | 12 |
Baseline characteristics
| Characteristic | Total | Methylphenidate | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 79 Participants | 40 Participants | 39 Participants |
| Age Continuous | 36.8 years STANDARD_DEVIATION 11.5 | 35.6 years STANDARD_DEVIATION 11 | 38.0 years STANDARD_DEVIATION 11.9 |
| Cigarettes Per Day | 20.2 cigarettes per day STANDARD_DEVIATION 7.8 | 19.7 cigarettes per day STANDARD_DEVIATION 7.4 | 20.8 cigarettes per day STANDARD_DEVIATION 8.2 |
| Region of Enrollment United States | 80 participants | 40 participants | 40 participants |
| Sex: Female, Male Female | 46 Participants | 20 Participants | 26 Participants |
| Sex: Female, Male Male | 34 Participants | 20 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 17 / 40 | 5 / 40 |
| serious Total, serious adverse events | 0 / 40 | 1 / 40 |
Outcome results
Primary
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)
Time frame: 6 months
Population: Intention to treat (ITT). subject who discontinued study participation were counted as using tobacco.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Methylphenidate | Number of Subjects Biochemically Confirmed to be Abstinent From Smoking at End of Study | 4 participants |
| Placebo | Number of Subjects Biochemically Confirmed to be Abstinent From Smoking at End of Study | 3 participants |
p-value: 0.5Fisher Exact
Primary
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)
Time frame: 8 weeks
Population: Intention to Treat. subjects with missing information were assumed to be using tobacco.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Methylphenidate | Number of Subjects Biochemically Confirmed to be Abstinent From Smoking at End of Treatment. | 1 participants |
| Placebo | Number of Subjects Biochemically Confirmed to be Abstinent From Smoking at End of Treatment. | 4 participants |
p-value: 0.973Fisher Exact
Secondary
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).
Time frame: baseline and 14 days
Population: Analysis was restricted to subjects who had diary information available for the first 14 days following target quit date
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methylphenidate | The Change in the Average Nicotine Withdrawal Symptom Score From Baseline to 14 Days Post Target Quit Date. | 0.28 units on a scale | Standard Deviation 0.42 |
| Placebo | The Change in the Average Nicotine Withdrawal Symptom Score From Baseline to 14 Days Post Target Quit Date. | 0.24 units on a scale | Standard Deviation 0.35 |
p-value: 0.65t-test, 2 sided
p-value: 0.79Mixed Models Analysis