CTN Research Update

National Advisory Council on Drug Abuse

May 8, 2013

Betty Tai, Ph.D.

Center for the Clinical Trials Network

CTN Steering Committee

B. Tai 2013

B. Tai 2013

NIDA - CCTN

NIDA National Drug Abuse Treatment Clinical Trials Network (CTN)

CTN goals and projects are aligned

with NIDA priorities:

• Revive medical involvement in drug abuse treatment

• Translate research into practice

• Increase and enhance the use of the CTN as a platform for additional types of research and training

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J F M A M J J A S O N D J F M A M J J A S O N D J F M A M J J A S O N D J F M A M J J A S O

CHOICES (CTN0055)

ADAPT-MD (CTN0054)

ACCENT (CTN0053)

BRAC-Main (CTN0058)

BRAC-Pilot (CTN0052)

X:BOT (CTN0051)

START F/UP (CTN0050)

HOPE (CTN0049)

CURB (CTN0048)

SMART-ED (CTN0047)

STRIDE (CTN0037)

POATS F/UP (CTN0030A3)

Timeline for Active and Upcoming CTN Trials Revised 05/06/2013

Concept/Protocol Development Preparation for Implementation Randomization Treatment+Follow-up of Last Participant Data Lock

2013 2014 2016 2015

B. Tai 2013

Pharmacotherapy to Treat SUD: Efficacy/Effectiveness Studies

CTN-0048 CURB: Cocaine Use Reduction with Buprenorphine

CTN-0052 BRAC: Buspirone for Relapse-Prevention in Adults with Cocaine Dependence

CTN-0053 ACCENT: Achieving Cannabis Cessation – Evaluating N-Acetylcysteine Treatment

CTN-0054 ADAPT-MD: Accelerated Development of Additive Pharmacotherapy Treatment for Methamphetamine Dependence

B. Tai 2013

CTN-0048 CURB: Cocaine Use Reduction with Buprenorphine

• PI: Walter Ling, M.D. (UCLA/CTN Pacific Region Node)

• Aim is to assess the safety and effectiveness of buprenorphine (BUP), in the presence of extended release naltrexone (XR-NTX), for the treatment of cocaine dependence

• Participants are cocaine-dependent adults with opioid use/abuse/dependence history

• Randomization to receive 8 weeks of:

1. XR-NTX + 16 mg BUP

2. XR-NTX + 4 mg BUP

3. XR-NTX + placebo

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• Trial enrolled 302 participants at 11 sites, from September 2011 to November 2012

• Last follow-up visit completed March 2013

• Database lock anticipated in May 2013

• Final study report anticipated in September 2013

B. Tai 2013

CTN-0048 CURB: Cocaine Use Reduction with Buprenorphine

B. Tai 2013

Pharmacotherapy to Treat SUD: Comparative Effectiveness Studies

CTN-0051 X:BOT: Extended-Release Depot Naltrexone vs. Buprenorphine for Opioid Treatment

CTN-0054 ADAPT-MD: Combine Extended Release Depot Naltrexone + Bupropion vs. Matched Placebos for Methamphetamine Dependence

CTN-0055 CHOICES: Comparing Treatments for HIV-Infected Opioid and Alcohol Users in an Integrated Care Effectiveness Study

Potential lives saved through quality improvement—the “break-even

point” for a drug that reduces mortality by 20 percent

Woolf & Johnson: Annals of Family Medicine 2005; 3(6):545–552

The Break-Even Point

B. Tai 2013

October 13, 2010: FDA approved Vivitrol® (extended-release injectable naltrexone) for the treatment of opioid dependence

B. Tai 2013

Vivitrol®

• Already marketed for alcohol dependence

• Potential for other indications

• Combination with other medications

• Place in spectrum of available treatments: compared to methadone and buprenorphine

• Limited to special patient populations?

B. Tai 2013

Adjunctive Treatments for SUD Specialty Care Providers

CTN-0037 STRIDE: Stimulant Reduction Intervention Using Dosed Exercise

CTN-0044 Web-Delivery of Evidence-Based Psychosocial Treatment for SUD

CTN-0046 S-CAST: Smoking Cessation and Stimulant Treatment

B. Tai 2013

CTN-0044 Web-Delivery of Evidence-Based Treatment for SUD

• PI: Edward Nunes, M.D. (Columbia/CTN Greater New York Node)

• Participants are adults seeking outpatient treatment for substance abuse—minimal exclusionary criteria

• Random assignment:

1. Treatment as Usual (TAU)

2. Modified TAU + Therapeutic Education System (TES)

TES substituted for 2 hours/week of usual clinician-delivered treatment

• 10 sites enrolled a total of 507 participants

Comprehensive, computer-assisted, psychosocial treatment

delivered by internet:

• Based on Community Reinforcement Approach & Contingency

Management

• Automated web-based platform—high dissemination potential

• 32 core modules (~weeks 1-8)

• 30 optional modules (~weeks 9-12)

• Prize-based incentives targeting abstinence and module

completion

B. Tai 2013

Therapeutic Education System (TES) (Bickel, Marsch et al., Exp Clin Psychopharm, 2008)

CTN-0044

• TES at least as good as TAU among participants abstinent at baseline

• TES doubles abstinence (OR=2.18) among participants non-abstinent at baseline

• TES also reduced dropout from treatment (HR=0.72)

CTN-0044 Results

Non-abstinent at

baseline

Abstinent at

baseline

• NIDA & SAMHSA

• Product Plan July 1, 2013

• Target Audiences

• Primary care and integrated care

providers (e.g., FQHCs and hospital

settings)

• Addiction & specialty treatment

providers

• Product Launch Summer 2014

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Blending Team & Plan

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HIV

CTN-0049 HOPE: Hospital Visit as Opportunity for Prevention and Engagement for HIV-Infected Drug Users

CTN-0055 CHOICES: Comparing Treatments for HIV-Infected Opioid and Alcohol Users in an Integrated Care Effectiveness Study

CTN-0056-Ot Testing and Linkage to HIV Care in China

Project AWARE HIV Rapid Testing and Counseling in STD Clinics in the U.S.

PI: Lisa Metsch, Ph.D. (Columbia/CTN Florida Node Alliance)

AIM: To evaluate strategies for achieving HIV virologic suppression among HIV-infected drug users recruited from the hospital setting

B. Tai 2013

CTN-0049 HOPE: Hospital Visit as

Opportunity for Prevention and Engagement

for HIV-Infected Drug Users

INTERVENTION

COVARIATES Socio-demographics

Housing Mental health status Alcohol & drug use

History of HIV primary care History of ART

Perceived health status History of Drug Treatment

Moderating effect

Primary Outcome

Proximal Outcome

Mechanism of main effect

VIROLOGIC SUPPRESSION

ART ADHERENCE

SUBSTANCE ABUSE

TREATMENT

Use of PRIMARY

CARE

B. Tai 2013

CTN-0049 HOPE Conceptual Model

• Participant-level randomization

• 800 HIV-infected inpatients to be randomized at 10 sites

(hospitals) in the U.S.

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CTN-0049 HOPE: Overview

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Long-Term Follow-Up Studies

CTN-0030-A3 Long-Term Follow-Up of the Prescription Opioid Addiction Treatment Study (POATS)

CTN-0050 Long-Term Follow-Up of the Starting Treatment with Agonist Replacement Therapies (START) Study

“Treatment of addiction should follow a chronic model of disease and maintain continued care for patients tailored to the severity and the substance abused.”

Volkow N.D. & Li, T.K. Nature Neuroscience 8 (11), 1429 (2005)

N. Volkow: NIDA Blending Conference, 2010

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Chronic Care Management for Substance Use

Unreachable Star?

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• Mandates that benefits measure up to medical and surgical

benefits

• Affordable Care Act (2010)

• Children’s Health Insurance Program Reauthorization Act

(2009)

• Mental Health Parity and Addiction Act (2008)

• Requires essentially all health plans to offer, by 2014:

• Prevention,

• Early intervention, and

• Treatment –for the full spectrum of “substance use

disorders”

B. Tai 2013

Recent U.S. Health Care Reform Legislation

Drives SUD care to primary care settings for initial

identification and treatment

Supports a chronic care model for all diseases (e.g.,

diabetes, hypertension, SUD)

Requires outcome measures in a recovery/relapse

disease model vs. just acute episodic care

B. Tai 2013

How Recent U.S. Health Care Reform Legislation Impacts SUD Care

• Physician visits

• Clinic visits

• Home health visits

• Insulin and 4 other meds

• Glucose tests, monitors, supplies

• HbA1c, eye, foot exams 4x/year

• Smoking cessation

• Personal care visits

• Language interpreter

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Medical Benefit for Diabetes Care

NIDA Taskforce on Chronic Care Management for SUD in Primary Care

2012

Lead: Dr. Tom McLellan

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Diagnostic Prevalence

“Harmful Use”

~ 45,000,000

Qualify!

Little or No Use Little/No Use

Very

Serious

Use

In Treatment ~ 2,300,000

~12% more

Qualify!

B. Tai 2013

US Health Reform

Affordable Care Act 2010

Very Rare

Use

Very Frequent

Use

Major NEW Role

For Primary Care

Expanded Role

For Specialty Care

B. Tai 2013

Very Rare

Use

Very Frequent

Use

Prevention & Early Intervention

Office-Based PC Treatment

Chronic Care Model

Care of Substance Use Disorders

B. Tai 2013

• To bring clinicians and researchers together to focus on real-world patients with multi-faceted health conditions

• For the following four goals:

• Natural history of a disease

• Treatment effectiveness

• Patient safety

• Health care process quality improvement (Federal Register, Feb 2012 ref)

B. Tai 2013

NIDA Taskforce on Chronic Care Management for SUD

1

Develop and adopt Electronic Health Records (EHRs) to facilitate:

1. Screening and Brief Interventions (SBI) in primary care

2. Registries to define parameters for Chronic Care Management research

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For now (until research findings arrive)

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CTN-0047 SMART-ED: Screening, Motivational Assessment,

Referral, and Treatment in Emergency Departments

Southwest & Pacific Northwest Nodes

Lead Investigators: Michael Bogenschutz, M.D. & Dennis Donovan, Ph.D.

Project Director: Alyssa Forcehimes, Ph.D.

Multiple Chronic Conditions

http://www.hhs.gov/ash/initiatives/mcc/ B. Tai 2013

• Among adults with diabetes:

• Approximately 20% are current cigarette smokers

• 50-60% are current alcohol users

• Adults with diabetes and comorbid substance use disorders have a high risk for:

• Developing and experiencing additional medical comorbidities and hospital readmissions

• More adverse outcomes

U.E. Ghitza, L.T. Wu, B. Tai. Substance Abuse Rehabilitation 2013; 4:3-10.

B. Tai 2013

Prevalence of Substance Use among Adults with Diabetes

B. Tai 2013

CTN-0057-Ot SBIRT-PC: Screening, Brief Intervention,

and Referral to Treatment in Primary Care

An add-on study to Duke University’s Southeastern Diabetes

Initiative, a CMS Innovation Award Project

CTN-INVEST Fellowship

• 12-month term

• Since 2007, 16 fellows from 14 countries

Mexico

• Established a network to conduct SUD clinical trials modeled on the CTN

• Funded by Dept. of State, working with researchers from Univ. of Miami

• Successfully completed a pilot RCT based on CTN-0021 study; second protocol to follow

Italy

• MOU with Italian government

• Funds for fellowships within CTN

• Provided faculty for Italian national SUD counselor training

Canada

• Major consultation for CIHR’s CTN

• UBC—a site for CTN-0055 pilot study

China

• CTN-0056-Ot platform study

Peru

• MOU in development follows Italian model

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International Collaborations: Research and Training

• Public website (www.ctndatashare.com) for 29 completed CTN studies

• Posted no later than 18 months after data lock or acceptance of the primary manuscript

• Clinical Data Interchange Standards Consortium (CDISC) format or

• Case Report Form (CRF) format

• Researchers (from 44 countries) have downloaded de-identified data from completed CTN studies (2,000 hits)

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NIDA-CTN Data Share

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The CTN Dissemination Library

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• Broader range of SUD patients

• Co-morbidities, poly-drug use problems

• Long-term outcomes vs. acute or short-term treatment

• Larger database (N>>10,000) vs. small database (N<< few 100s)

• Risks/benefits

• Cost-effectiveness

B. Tai 2013

Longitudinal Disease and Treatment Registry for SUD: Why?