Transcript Randomized Controlled Trial of Osmotic

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 cooccurring 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
Site
Pre-Screened
(n)
Consented
(n)
Randomized
(n)
Avg
Randomized
per week
Synergy,
UCHSC
9
4
3
0.253
LRADAC, SC
8
(0.49)
2
2
0.169
(0.49)
SSTAR, NNE
17
7
4
0.337
(0.49)
Total
34
13
9
0.759
(1.47)
Referral Sources - Wave 1
Pre-Screen Ineligibility-Wave 1
Medication Tolerability - Wave 1
Site
Randomized
%
% Med
Reaching
Dose
Target Reduction
Dose
Synergy, UCHSC
3
100%
50%
LRADAC, SC
2
100%
0%
SSTAR, NNE
4
100%
14.3%
Total
9
100%
20%
Study Timeline & Enrollment Schedule
2006
A/4 M/5
6 12
2007
J/1 F/2
midpoint 153
175
S/9
J/6
18
J/7
21
A/8
43
S/9 O/10 N/11 D/12
65
87 109 131
M/3 A/4Initial projection
M/5 enrollment
J/6 completion
J/7 A/8
197 219 241 263 285 307
O/10 N/11 D/12
16 wk study completion
2008
J/1 F/2
M/3
A/4
F/u study completion Study close out, data lock, manuscript preparation
enrollment completed