ADHD, Smoking
Conditions
Brief summary
The objective of this study is to evaluate whether Osmotic-Release Methylphenidate (OROS MPH), relative to placebo, increases the effectiveness of standard smoking treatment (i.e., nicotine patch and individual smoking cessation counseling) in obtaining prolonged abstinence for smokers with Attention Deficit Hyperactivity Disorder (ADHD).
Detailed description
The primary objective of this study is to evaluate whether OROS MPH (Concerta), relative to placebo, increases the effectiveness of standard smoking treatment (i.e., nicotine patch and individual smoking cessation counseling) in obtaining prolonged abstinence for smokers with ADHD. The study will involve an estimated 252 participants, recruited from approximately 6 sites.
Interventions
DRUGOsmotic-Release Methylphenidate
OROS-MPH dosing strategy will start with 18 mg/day for 3 days, increasing to 36mg/day for the next three days; increasing to 54 mg/day in week two, and to 72 mg/day in week three through the remainder of the study (as tolerated). And, nicotine patch dosing schedule will be 21 mg/day during weeks 4-11; 14 mg/day during weeks 12-13; and 7 mg/day in week 14.
DRUGPlacebo
OROS-MPH (placebo) dosing strategy will start with 18 mg/day for 3 days, increasing to 36mg/day for the next three days; increasing to 54 mg/day in week two, and to 72 mg/day in week three through the remainder of the study (as tolerated). And, nicotine patch dosing schedule will be 21 mg/day during weeks 4-11; 14 mg/day during weeks 12-13; and 7 mg/day in week 14.
Sponsors
National Institute on Drug Abuse (NIDA)
Ortho-McNeil Janssen Scientific Affairs, LLC
University of Cincinnati
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 55 Years
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of ADHD2 * Smoked cigarettes for at least 3 months * Currently smoking \> 10 cigarettes/day * Have an interest in quitting * Negative urine screen for cocaine, methamphetamine, opiates, benzodiazepines, and marijuana
Exclusion criteria
* Have a clinical diagnosis for current abuse or dependence for any psychoactive substance other than nicotine, depression, or anxiety; or a life-time clinical diagnosis of psychosis or bipolar disorder * Allergic to OROS-MPH * Pregnant or breastfeeding * Abnormal electrocardiogram (ECG) * Taking a Monoamine Oxidase (MAO) Inhibitor * Taking any medication used for treating either ADHD or smoking * Use of tobacco products other than cigarettes in the past week * Blood pressure readings greater than 135/85 and/or a heart rate more than 90 beats per minute on three consecutive clinic visits
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prolonged Abstinence | Weeks 7-10 | The smoking quit date was considered the first day of the O-MPH/P-Stnd Smoking Tx phase, which lasted for 6 weeks or more precisely 42 days (i.e., approximately weeks 5-10). The grace period was the first two weeks (i.e., days 1-14) with the remaining four weeks (days 15-42) comprising the period in which the participant must not meet criteria for treatment failure in order to be scored as obtaining prolonged abstinence. Self-report of cigarette use was assessed using a time-line follow-back (TLFB) assessment using carbon monoxide (CO)levels to correct self-reported smoking days. Smoking days were determined by starting with self-reported smoking and non-smoking days and using CO levels measured at weekly visits to modify the self-reports. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Diagnostic and Statistical Manual-IV(DSM-IV) ADHD Rating Scale | Baseline and Study weeks 1,4,7,9,11 | A Generalized Estimating Equations(GEE)model which included treatment group, week, site, and treatment by week and site by week interaction effects was used to compare the groups on the DSM-IV ADHD total severity score (18 domains score at severity levels of 0\[none\]-3\[severe\]; maximum score 54) as measured at screening/baseline and study weeks 1-4 using the the interviewer-administered DSM-IV checklist and by the severity portion of the National Institute of Mental Health Clinical Global Impression (CGI) scale to rate the severity of the participant's ADHD symptoms. A single severity score ranging from 1 to 7 is yielded by the CGI severity scale. |
| Point-prevalence Abstinence | Week 11 | A logistic regression including site and treatment group will be used to model rates of achieving point prevalence abstinence as assessed at the final visit of the O-MPH/P-Stnd Smoking Tx phase. Point prevalence abstinence was defined as not smoking in the previous seven days based on self-report using the TLFB method and confirmed with a Carbon Monoxide (CO) level \<8 ppm. |
Countries
United States
Participant flow
Recruitment details
This trial was conducted by the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) between December 2005 and January 2008. Six study sites recruited participants: 2 substance abuse community treatment programs, 2 Attention Deficit Hyperactivity Disorder (ADHD) clinics and 2 smoking cessation clinics.
Participants by arm
| Arm | Count |
|---|---|
| Osmotic-Release Methylphenidate (OROS-MPH) For OROS-MPH, the starting dose of 18 mg/day was escalated during the first two study weeks to a maximum of 72 mg/day or to the highest dose tolerated. A trained interventionist provided each participant with a weekly 10 minute smoking cessation counseling session during study weeks 1-11. All participants received transdermal nicotine patches. | 127 |
| Osmotic-Release Methylphenidate (OROS-MPH) - Placebo OROS-MPH/placebo was taken through the week 11 visit. A trained interventionist provided each participant with a weekly 10 minute smoking cessation counseling session during study weeks 1-11. All participants received transdermal nicotine patches. | 128 |
| Total | 255 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative Discharge (1), Other (2) | 1 | 2 |
| Overall Study | Lost to Follow-up | 13 | 14 |
| Overall Study | Withdrawal by Subject | 10 | 11 |
Baseline characteristics
| Characteristic | Osmotic-Release Methylphenidate (OROS-MPH) - Placebo | Osmotic-Release Methylphenidate (OROS-MPH) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 128 Participants | 127 Participants | 255 Participants |
| Age Continuous | 37.5 years STANDARD_DEVIATION 9.6 | 38.1 years STANDARD_DEVIATION 10.4 | 37.8 years STANDARD_DEVIATION 10 |
| Region of Enrollment United States | 128 participants | 127 participants | 255 participants |
| Sex: Female, Male Female | 61 Participants | 50 Participants | 111 Participants |
| Sex: Female, Male Male | 67 Participants | 77 Participants | 144 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 35 / 127 | 28 / 128 |
| serious Total, serious adverse events | 2 / 127 | 0 / 128 |
Outcome results
Primary
Prolonged Abstinence
The smoking quit date was considered the first day of the O-MPH/P-Stnd Smoking Tx phase, which lasted for 6 weeks or more precisely 42 days (i.e., approximately weeks 5-10). The grace period was the first two weeks (i.e., days 1-14) with the remaining four weeks (days 15-42) comprising the period in which the participant must not meet criteria for treatment failure in order to be scored as obtaining prolonged abstinence. Self-report of cigarette use was assessed using a time-line follow-back (TLFB) assessment using carbon monoxide (CO)levels to correct self-reported smoking days. Smoking days were determined by starting with self-reported smoking and non-smoking days and using CO levels measured at weekly visits to modify the self-reports.
Time frame: Weeks 7-10
Population: Randomized participants who complete at least two visits during the first four weeks following randomization, who reach the full dose of OROS-MPH /Placebo, who have a OROS-MPH /placebo medication compliance rate of at least 75% each week for study weeks 4 through 10, and who attend at least one meeting after initiating the nicotine patch.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Osmotic-Release Methylphenidate (OROS-MPH) | Prolonged Abstinence | 25 participants |
| Osmotic-Release Methylphenidate (OROS-MPH) - Placebo | Prolonged Abstinence | 28 participants |
Secondary
Diagnostic and Statistical Manual-IV(DSM-IV) ADHD Rating Scale
A Generalized Estimating Equations(GEE)model which included treatment group, week, site, and treatment by week and site by week interaction effects was used to compare the groups on the DSM-IV ADHD total severity score (18 domains score at severity levels of 0\[none\]-3\[severe\]; maximum score 54) as measured at screening/baseline and study weeks 1-4 using the the interviewer-administered DSM-IV checklist and by the severity portion of the National Institute of Mental Health Clinical Global Impression (CGI) scale to rate the severity of the participant's ADHD symptoms. A single severity score ranging from 1 to 7 is yielded by the CGI severity scale.
Time frame: Baseline and Study weeks 1,4,7,9,11
Population: Evaluable participants determined using criteria for same in the primary outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Osmotic-Release Methylphenidate (OROS-MPH) | Diagnostic and Statistical Manual-IV(DSM-IV) ADHD Rating Scale | 38.4 DSM IV ADHD Score | Standard Deviation 7.6 |
| Osmotic-Release Methylphenidate (OROS-MPH) - Placebo | Diagnostic and Statistical Manual-IV(DSM-IV) ADHD Rating Scale | 36.6 DSM IV ADHD Score | Standard Deviation 7.7 |
| Osmotic-Release Methylphenidate (OROS-MPH)-Week 11 | Diagnostic and Statistical Manual-IV(DSM-IV) ADHD Rating Scale | 16.4 DSM IV ADHD Score | Standard Deviation 12.2 |
| Osmotic-Release Methylphenidate (OROS-MPH) - Placebo-Week 11 | Diagnostic and Statistical Manual-IV(DSM-IV) ADHD Rating Scale | 24.2 DSM IV ADHD Score | Standard Deviation 23 |
| Release Methylphenidate (OROS-MPH)-Week 4 | Diagnostic and Statistical Manual-IV(DSM-IV) ADHD Rating Scale | 20.4 DSM IV ADHD Score | Standard Deviation 12.6 |
| Osmotic-Release Methylphenidate (OROS-MPH) - Placebo-Week 4 | Diagnostic and Statistical Manual-IV(DSM-IV) ADHD Rating Scale | 27.2 DSM IV ADHD Score | Standard Deviation 12 |
| Release Methylphenidate (OROS-MPH)-Week 7 | Diagnostic and Statistical Manual-IV(DSM-IV) ADHD Rating Scale | 20 DSM IV ADHD Score | Standard Deviation 12.6 |
| Osmotic-Release Methylphenidate (OROS-MPH) - Placebo-Week 7 | Diagnostic and Statistical Manual-IV(DSM-IV) ADHD Rating Scale | 24 DSM IV ADHD Score | Standard Deviation 13.3 |
| Release Methylphenidate (OROS-MPH)-Week 9 | Diagnostic and Statistical Manual-IV(DSM-IV) ADHD Rating Scale | 17.3 DSM IV ADHD Score | Standard Deviation 12.6 |
| Methylphenidate (OROS-MPH) - Placebo-Week 9 | Diagnostic and Statistical Manual-IV(DSM-IV) ADHD Rating Scale | 23.9 DSM IV ADHD Score | Standard Deviation 13.6 |
Secondary
Point-prevalence Abstinence
A logistic regression including site and treatment group will be used to model rates of achieving point prevalence abstinence as assessed at the final visit of the O-MPH/P-Stnd Smoking Tx phase. Point prevalence abstinence was defined as not smoking in the previous seven days based on self-report using the TLFB method and confirmed with a Carbon Monoxide (CO) level \<8 ppm.
Time frame: Week 11
Population: Evaluable population determined as for primary outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Osmotic-Release Methylphenidate (OROS-MPH) | Point-prevalence Abstinence | 24 participants |
| Osmotic-Release Methylphenidate (OROS-MPH) - Placebo | Point-prevalence Abstinence | 26 participants |