Title: Randomized%20Controlled%20Trial%20of%20Osmotic-Release%20Methylphenidate%20(OROS%20MPH)%20for%20Attention%20Deficit%20Hyperactivity%20Disorder%20(ADHD)%20in%20Adolescents%20with%20Substance%20Use%20Disorders%20(SUD)%20(NIDA-CTN-0028)
1Study Design for a Randomized Controlled Trial
of Osmotic-Release Methylphenidate
(OROS-MPH) for Attention Deficit
Hyperactivity Disorder in Adolescents
with Substance Use Disorders
Presenter Theresa Winhusen, Ph.D.
June 14, 2006, Pharmacological Treatment of ADHD
in Substance-Abusing Adolescents and Adults New
Findings, Research Directions, and Clinical
Implications 310 330
2Principal Investigators
- Principal Investigator
- Paula Riggs MD University of Colorado at Denver
Health Sciences Center (UCDHSC) - Co-Principal Investigators
- Theresa Winhusen PhD
- Robert Davies MD, Medical Co LI (UCDHSC)
3Background Significance
- 30-50 of adolescents in substance treatment have
ADHD - ADHD associated with
- More severe substance abuse
- Worse behavior problems
- Poorer treatment outcomes
4Background Significance
- Integrated treatment is considered to be a core
drug treatment principle (NIDA, 1999) - Recent community treatment survey
- lt 50 had dual diagnosis programs
- Of those with dual diagnosis programs
- 43.4 did not offer prescription meds
- 37.8 did not offer psychiatric/psychological
evaluation - Motjabai, 2004
5Background Significance
- One RCT targeting ADHD in adolescents with
co-occurring SUD - 12 week trial pemoline n69, adolescents 13-19
- Similar safety, efficacy for ADHD as in
adolescents without SUD - No impact on drug use in the ABSENCE of specific
substance treatment -
Riggs et al 2004
Schedule 1V psychostimulant
6Treatment of ADHD /- SUD
- Schedule II psychostimulants, gold standard
- Non-scheduled alternatives-- bupropion and
atomoxetine-- have lower effect sizes (.5 and .7) - OROS-MPH/Concerta
- Long acting (12 hours) once daily dosing
- Equivalent efficacy to short acting
psychostimulants - Controlled delivery system likely reduces abuse
potential
7Standardized SUD Treatment
- Individual Manualized Cognitive Behavioral
- Therapy (CBT)
- Found effective for SUD in adolescents
- Individual, not group, due to feasibility
- 16 sessions, including up to 3 family
- sessions
8Study Objectives
- Primary Objectives
- 1a Evaluate safety and efficacy of OROS-MPH vs.
Placebo for ADHD in adolescents with SUD - 1b Evaluate impact of treatment of ADHD with
OROS-MPH on substance treatment outcomes
9Study Design
- 16-week randomized controlled trial
- OROS-MPH (72mg/day) vs placebo
- CBT for SUD
- Weekly
- Outpatient
- Power
- N 300 to detect low/medium effect size (.4)
- 11 study sites
-
10Study Sites
- Wave 1
- LRADAC, South Carolina
- Synergy, Colorado
- STARR, Northern New England
- Wave 2
- Operation PAR, Florida
- Gateway, Florida
- Mountain Manor, Mid-Atlantic
- Crittenton, Ohio Valley
- St Lukes Roosevelt, Long Island
- MHMR of Tarrant County, Texas
- Rehab After Work, Delaware Valley
- Addiction Medicine Services, Appalachian Tri
State
11Study Participants
- Participants
- Inclusion
- Adolescents (13-18)
- DSM IV ADHD
- At least one SUD
- Exclusion
- serious medical illness
- bipolar
- psychosis
- opiate dependence
- methamphetamine abuse, dependence
- other treatment psychotropics
12Primary Outcome Measures
- DSM-IV ADHD Symptom Checklist
- Number of Use Days
- -Substance Use Self-Report using the TLFB
13Other Efficacy Measures
- ADHD
- Clinician Global Impression of
- Improvement (CGI-I) Rating Scale
- Substance Use Outcomes
- Frequency of Drug Use (TLFB)
- Urine Toxicology
- Proportion of Negative Urines
14Safety Measures
- Vital Signs/Weight
- Pregnancy Test
- Adverse Events
- Prior/Concomitant Medications
- Lab values (urinalysis, CBC, LFTs)
15Study Progress
- Wave 1 Sites Initiated March 2006
- Wave 2 Site Initiation June-July 2006
16 Study Progress - Wave 1
17 Referral Sources - Wave 1
18Pre-Screen Ineligibility-Wave 1
19Medication Tolerability - Wave 1
20Study Timeline Enrollment Schedule
-
- 2006
- A/4 M/5 J/6 J/7 A/8 S/9 O/10 N/11
D/12 - 6 12 18 21 43 65 87
109 131 - 2007
- J/1 F/2 M/3 A/4 M/5 J/6 J/7
A/8 - 153 175 197 219 241 263 285 307
- S/9 O/10 N/11 D/12
- 2008
- J/1 F/2 M/3 A/4
Initial projection enrollment completion
midpoint
enrollment completed
16 wk study completion
F/u study completion
Study close out, data lock, manuscript preparation