Post on 02-Jan-2016
transcript
Study Design for a Randomized Controlled Trial ofStudy Design for a Randomized Controlled Trial of Osmotic-Release Methylphenidate (OROS-MPH)Osmotic-Release Methylphenidate (OROS-MPH) for Attention Deficit Hyperactivity Disorderfor Attention Deficit Hyperactivity Disorder in Adolescents with Substance Use Disordersin Adolescents with Substance Use Disorders
June 14, 2006, Pharmacological Treatment of ADHD in Substance-Abusing Adolescents and Adults: New Findings, Research Directions, and Clinical Implications: 3:10 – 3:30
Presenter: Theresa Winhusen, Ph.D.
Principal InvestigatorsPrincipal 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)
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 & SignificanceBackground & Significance
30-50% of adolescents in substance treatment have ADHD
ADHD associated with: More severe substance abuse Worse behavior problems Poorer treatment outcomes
30-50% of adolescents in substance treatment have ADHD
ADHD associated with: More severe substance abuse Worse behavior problems Poorer treatment outcomes
Integrated treatment is considered to be a core drug Integrated treatment is considered to be a core drug treatment principle (NIDA, 1999)treatment principle (NIDA, 1999)
Recent community treatment surveyRecent community treatment survey < 50% had “dual diagnosis” programs< 50% had “dual diagnosis” programs Of those with dual diagnosis programs:Of those with dual diagnosis programs:
43.4% did not offer prescription meds43.4% did not offer prescription meds
37.8% did not offer psychiatric/psychological evaluation37.8% did not offer psychiatric/psychological evaluationMotjabai, Motjabai,
20042004
Integrated treatment is considered to be a core drug Integrated treatment is considered to be a core drug treatment principle (NIDA, 1999)treatment principle (NIDA, 1999)
Recent community treatment surveyRecent community treatment survey < 50% had “dual diagnosis” programs< 50% had “dual diagnosis” programs Of those with dual diagnosis programs:Of those with dual diagnosis programs:
43.4% did not offer prescription meds43.4% did not offer prescription meds
37.8% did not offer psychiatric/psychological evaluation37.8% did not offer psychiatric/psychological evaluationMotjabai, Motjabai,
20042004
Background & SignificanceBackground & 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
Background & SignificanceBackground & Significance
Treatment of ADHD +/-SUD
Treatment of ADHD +/-SUD
Schedule II psychostimulants, gold standardSchedule II psychostimulants, gold standard Non-scheduled alternatives-- bupropion and Non-scheduled alternatives-- bupropion and
atomoxetine-- have lower effect sizes (.5 and .7)atomoxetine-- have lower effect sizes (.5 and .7)
OROS-MPH/Concerta OROS-MPH/Concerta Long acting (12 hours); once daily dosingLong acting (12 hours); once daily dosing Equivalent efficacy to short acting psychostimulantsEquivalent efficacy to short acting psychostimulants Controlled delivery system likely reduces abuse Controlled delivery system likely reduces abuse
potentialpotential
Schedule II psychostimulants, gold standardSchedule II psychostimulants, gold standard Non-scheduled alternatives-- bupropion and Non-scheduled alternatives-- bupropion and
atomoxetine-- have lower effect sizes (.5 and .7)atomoxetine-- have lower effect sizes (.5 and .7)
OROS-MPH/Concerta OROS-MPH/Concerta Long acting (12 hours); once daily dosingLong acting (12 hours); once daily dosing Equivalent efficacy to short acting psychostimulantsEquivalent efficacy to short acting psychostimulants Controlled delivery system likely reduces abuse Controlled delivery system likely reduces abuse
potentialpotential
Standardized SUD TreatmentStandardized 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 ObjectivesStudy 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 DesignStudy Design
16-week randomized controlled trial 16-week randomized controlled trial
OROS-MPH (72mg/day) vs placeboOROS-MPH (72mg/day) vs placebo CBT for SUDCBT for SUD
WeeklyWeekly OutpatientOutpatientPowerPower
N= 300 to detect low/medium effect size (.4)N= 300 to detect low/medium effect size (.4) 11 study sites11 study sites
Study SitesStudy Sites
Wave 1 Wave 1 • LRADAC, South CarolinaLRADAC, South Carolina• Synergy, ColoradoSynergy, Colorado• STARR, Northern New EnglandSTARR, Northern New England
Wave 2 Wave 2 • Operation PAR, FloridaOperation PAR, Florida• Gateway, FloridaGateway, Florida• Mountain Manor, Mid-AtlanticMountain Manor, Mid-Atlantic• Crittenton, Ohio Valley Crittenton, Ohio Valley • St Lukes Roosevelt, Long Island St Lukes Roosevelt, Long Island • MHMR of Tarrant County, TexasMHMR of Tarrant County, Texas• Rehab After Work, Delaware ValleyRehab After Work, Delaware Valley• Addiction Medicine Services, Appalachian Tri StateAddiction Medicine Services, Appalachian Tri State
Study ParticipantsStudy Participants
ParticipantsInclusion
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 MeasuresPrimary Outcome Measures
DSM-IV ADHD Symptom ChecklistDSM-IV ADHD Symptom Checklist
Number of Use Days
-Substance Use Self-Report using the TLFBSubstance Use Self-Report using the TLFB
Other Efficacy MeasuresOther Efficacy Measures
ADHDADHD Clinician Global Impression of Clinician Global Impression of Improvement (CGI-I) Rating ScaleImprovement (CGI-I) Rating Scale
Substance Use OutcomesSubstance Use Outcomes Frequency of Drug Use (TLFB)
Urine Toxicology
• Proportion of Negative Urines
Safety MeasuresSafety Measures
Vital Signs/WeightVital Signs/Weight
Pregnancy TestPregnancy Test
Adverse EventsAdverse Events
Prior/Concomitant MedicationsPrior/Concomitant Medications
Lab values (urinalysis, CBC, LFTs)Lab values (urinalysis, CBC, LFTs)
Wave 1 Sites Initiated March 2006
Wave 2 Site Initiation June-July 2006
Wave 1 Sites Initiated March 2006
Wave 2 Site Initiation June-July 2006
Study ProgressStudy Progress
20062006
A/4 M/5 J/6 J/7 A/8 S/9 O/10 N/11 D/12A/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 6 12 18 21 43 65 87 109 131
20072007
J/1 F/2 M/3 A/4 J/1 F/2 M/3 A/4 M/5 J/6M/5 J/6 J/7 J/7 A/8A/8
153153 175 197 219 241 263 285 175 197 219 241 263 285 307307 S/9 O/10 N/11 S/9 O/10 N/11 D/12D/12
20082008
J/1J/1 F/2 M/3 A/4F/2 M/3 A/4
20062006
A/4 M/5 J/6 J/7 A/8 S/9 O/10 N/11 D/12A/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 6 12 18 21 43 65 87 109 131
20072007
J/1 F/2 M/3 A/4 J/1 F/2 M/3 A/4 M/5 J/6M/5 J/6 J/7 J/7 A/8A/8
153153 175 197 219 241 263 285 175 197 219 241 263 285 307307 S/9 O/10 N/11 S/9 O/10 N/11 D/12D/12
20082008
J/1J/1 F/2 M/3 A/4F/2 M/3 A/4
Study Timeline & Enrollment Schedule Study Timeline & Enrollment Schedule
midpoint
enrollment completed
F/u study completion Study close out, data lock, manuscript preparation
Initial projection enrollment completion
16 wk study completion16 wk study completion