ADHD, Substance Abuse
Conditions
Brief summary
The purpose of this study is to determine the efficacy of osmotic-release methylphenidate (OROS-MPH) versus placebo for the treatment of ADHD in adolescents with SUD.
Detailed description
Research shows a high prevalence of Attention Deficit Hyperactivity Disorder (ADHD) in adolescents with substance abuse disorders and indicates that they have poorer substance use treatment outcomes and poorer prognosis and risk of persistence and progression of drug use and behavior problems into adulthood. Although research indicates that the majority are not treated for ADHD while in substance treatment, we do not know whether concurrent pharmacotherapy for ADHD will improve treatment outcomes. This Clinical Trials Network (CTN) study will evaluate the efficacy of osmotic-release methylphenidate (OROS-MPH), relative to placebo, in treating ADHD and decreasing substance use in adolescents (13-18 years old) with ADHD and a substance use disorder. Approximately 300 participants will be recruited at 11 sites and randomly assigned to either OROS-MPH or matching placebo for a 16-week treatment period, during which all participants will receive individual cognitive-behavioral therapy as a standardized treatment for substance abuse.
Interventions
DRUGMethylphenidate (OROS-MPH)
Participants will be scheduled for weekly medication (OROS-MPH) and research assessment visits (approximately 45 minutes to 1 hour in length). A forced titration dosing strategy will be used starting with 18 mg/day OROS-MPH 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). Participants will also attend weekly CBT sessions (approximately 1 hour in length) targeting their drug use.
DRUGMethylphenidate (OROS-MPH) - Placebo
Participants will be scheduled for weekly medication and research assessment visits (approximately 45 minutes to 1 hour in length). A forced titration dosing strategy will be used starting with 18 mg/day OROS-MPH placebo 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). Participants will also attend weekly CBT sessions (approximately 1 hour in length) targeting their drug use.
Sponsors
National Institute on Drug Abuse (NIDA)
University of Colorado, Denver
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
13 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Meet Diagnostic and Statistical Manual for Mental Disorders, 4th Edition (DSM-IV) diagnostic criteria for ADHD * Meet DSM-IV diagnostic criteria for at least one non-nicotine substance use disorder * Has a DSM-IV ADHD Symptom Checklist score ≥ 22 derived from the adolescent-completed checklist
Exclusion criteria
* Serious medical illness * History of tic disorder * Pregnant or breastfeeding * Meet DSM-IV criteria for current or life-time psychotic disorder * Meet DSM-IV criteria for current or life-time bipolar disorder * Requires/or prescribed other concurrent psychotropic medication * Taking any medications that may produce interactions with OROS-MPH * Opiate dependence * Methamphetamine abuse or dependence * Suicidal risk * Enrolled in an inpatient, residential, day treatment, or outpatient substance abuse program within 28 days prior to signing consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ADHD Severity | baseline and 20 weeks | DSM IV ADHD Rating Scale (ADHD-RS) adolescent informant, ascertained at baseline and weekly throughout the 16 week study. This scale is an 18-item symptom checklist of self-reported adolescent ADHD symptoms. Symptoms are scored as None (0), Mild (1), Moderate (2), and Severe (3), with a summary total of scores for the 18 symptoms. Possible scores range from 0 to 54, with higher scores indicating greater severity. Outcome is measured as the decrease in total severity score over time. |
| Substance Use | 20 weeks | The change in number of days of substance use from baseline to end of the trial. The number of days of non-tobacco drug/alcohol ascertained using standard timeline follow back (TLFB) procedures. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| OROS-MPH Abuse Liability | 20 weeks | Assessed by pill counts in conjunction with weekly review of subjects' medication diaries and self-reported medication compliance. |
| Substance Use Outcomes | 20 weeks | The mean number of negative urine drug screens (UDS). |
Countries
United States
Participant flow
Recruitment details
This trial was conducted by the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) between March 2006 and October 2008. Eleven community based treatment programs recruited participants.
Participants by arm
| Arm | Count |
|---|---|
| Methylphenidate Methylphenidate (OROS-MPH) : Participants will be scheduled for weekly medication (OROS-MPH) and research assessment visits (approximately 45 minutes to 1 hour in length). A forced titration dosing strategy will be used starting with 18 mg/day OROS-MPH 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). Participants will also attend weekly CBT sessions (approximately 1 hour in length) targeting their drug use. | 151 |
| Methylphenidate (Placebo) Methylphenidate (OROS-MPH) - Placebo : Participants will be scheduled for weekly medication and research assessment visits (approximately 45 minutes to 1 hour in length). A forced titration dosing strategy will be used starting with 18 mg/day OROS-MPH placebo 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). Participants will also attend weekly CBT sessions (approximately 1 hour in length) targeting their drug use. | 152 |
| Total | 303 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Feels treatment not necessary, not worki | 0 | 1 |
| Overall Study | Incarceration | 4 | 5 |
| Overall Study | Lost to Follow-up | 9 | 17 |
| Overall Study | Moved from area | 3 | 1 |
| Overall Study | Other | 3 | 4 |
| Overall Study | Practical Problems | 2 | 3 |
| Overall Study | Pressure/advice from Outsiders | 1 | 1 |
| Overall Study | Withdrawal by Subject | 11 | 11 |
Baseline characteristics
| Characteristic | Methylphenidate (Placebo) | Methylphenidate | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 152 Participants | 151 Participants | 303 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age Continuous | 16.6 years STANDARD_DEVIATION 1.2 | 16.4 years STANDARD_DEVIATION 1.3 | 16.5 years STANDARD_DEVIATION 1.3 |
| Region of Enrollment United States | 152 participants | 151 participants | 303 participants |
| Sex: Female, Male Female | 35 Participants | 29 Participants | 64 Participants |
| Sex: Female, Male Male | 117 Participants | 122 Participants | 239 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 70 / 151 | 64 / 152 |
| serious Total, serious adverse events | 4 / 151 | 7 / 152 |
Outcome results
Primary
ADHD Severity
DSM IV ADHD Rating Scale (ADHD-RS) adolescent informant, ascertained at baseline and weekly throughout the 16 week study. This scale is an 18-item symptom checklist of self-reported adolescent ADHD symptoms. Symptoms are scored as None (0), Mild (1), Moderate (2), and Severe (3), with a summary total of scores for the 18 symptoms. Possible scores range from 0 to 54, with higher scores indicating greater severity. Outcome is measured as the decrease in total severity score over time.
Time frame: baseline and 20 weeks
Population: All randomized participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methylphenidate | ADHD Severity | -20.6 units on a scale | Standard Deviation 11.1 |
| Methylphenidate (Placebo) | ADHD Severity | -21.8 units on a scale | Standard Deviation 11.9 |
Primary
Substance Use
The change in number of days of substance use from baseline to end of the trial. The number of days of non-tobacco drug/alcohol ascertained using standard timeline follow back (TLFB) procedures.
Time frame: 20 weeks
Population: All randomized participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methylphenidate | Substance Use | -5.7 days | 95% Confidence Interval 0.8 |
| Methylphenidate (Placebo) | Substance Use | -5.2 days | 95% Confidence Interval 0.9 |
Secondary
OROS-MPH Abuse Liability
Assessed by pill counts in conjunction with weekly review of subjects' medication diaries and self-reported medication compliance.
Time frame: 20 weeks
Population: All randomized participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methylphenidate | OROS-MPH Abuse Liability | 15.4 pills | Standard Deviation 18.7 |
| Methylphenidate (Placebo) | OROS-MPH Abuse Liability | 9.7 pills | Standard Deviation 11.2 |
Secondary
Substance Use Outcomes
The mean number of negative urine drug screens (UDS).
Time frame: 20 weeks
Population: All randomized participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methylphenidate | Substance Use Outcomes | 3.8 negative UDS | Standard Deviation 4.9 |
| Methylphenidate (Placebo) | Substance Use Outcomes | 2.8 negative UDS | Standard Deviation 4.2 |