Study Design for a Randomized Controlled Trial of Osmotic-Release Methylphenidate (OROS-MPH) Osmotic-Release Methylphenidate (OROS-MPH) for Attention Deficit.

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

Study Progress - Wave 1 Study Progress - Wave 1

Referral Sources - Wave 1 Referral Sources - Wave 1

Pre-Screen Ineligibility-Wave 1Pre-Screen Ineligibility-Wave 1

Medication Tolerability - Wave 1Medication Tolerability - Wave 1

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