Study 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: 3:10 – 3:30
 Principal 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)
 Background & Significance

 30-50% of adolescents in substance treatment

have ADHD

 ADHD associated with:

 More severe substance abuse
 Worse behavior problems
 Poorer treatment outcomes
 Background & Significance

Integrated treatment is considered to be a core drug

treatment principle (NIDA, 1999)

Recent community treatment survey

 < 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
 Background & Significance

 One RCT targeting ADHD in adolescents with co-

occurring SUD

12 week trial pemoline* n=69, 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

 Treatment 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
 Standardized 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
 Study 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
 Study 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
 Study 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
 Study 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
 Primary Outcome Measures

 DSM-IV ADHD Symptom Checklist

 Number of Use Days

-Substance Use Self-Report using the TLFB
 Other 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
 Safety Measures

 Vital Signs/Weight
 Pregnancy Test
 Adverse Events
 Prior/Concomitant Medications
 Lab values (urinalysis, CBC, LFTs)
 Study Progress

 Wave 1 Sites Initiated March 2006

 Wave 2 Site Initiation June-July 2006

Study Progress - Wave 1
Referral Sources - Wave 1
Pre-Screen Ineligibility-Wave 1
Medication Tolerability - Wave 1
Study 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/4Initial projection
M/5 enrollment
J/6completion
J/7 A/8
midpoint 153 175 197 219 241 263 285 307
enrollment completed
S/9 O/10 N/11 D/12
16 wk study completion
16 wk study completion

2008
J/1 F/2 M/3 A/4
F/u study completion Study close out, data lock, manuscript preparation