CTN Pharmacotherapy Trials and the CTP

Allan J. Cohen, MA, MFTBay Area Addiction, Research and

Treatment, Inc(BAART)

Pacific Region Node

CTN 10th Anniversary SymposiumApril 21, 2010

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Growth of the CTN CTP Network

2000: 52 CTP - 6 Nodes

2002: 91 CTP - 14 Nodes 2005: 123 CTP – 17 Nodes 2010: 187 CTP -16 Nodes

• Total - 206 CTP have participated

Therapeutic Communities

OpioidTreatment Programs

Drug Free Intensive Outpatient

Short-term and Long-term Residential Care

Small Community Clinics

Large Urban Clinics

Hospital Based

University Based Programs

VA

Community Treatment Programs

• Many ways to classify CTP but one characteristic frequently used:

• Medication-assisted treatment (methadone/harm reduction)

• Traditionally do not utilize medications

( psychosocial, “drug free”, abstinence)

We address a broad array of addictions with a wide variety of treatment

interventions

“Wild Things” Group Therapy

Some very innovative treatment

approaches

Staff of earliest

recorded CTP

Staff of earliest

recorded CTP

Staff of earliest

recorded CTP

Staff of earliest

recorded CTP

Richard Drandoff

Pharmacotherapy Trails in CTP

Ten Medications Trials

• Six = Suboxone ( CTN 0001, 0002, 0003, 0010, 0027, 0030)

• Two = Methlyphenidate (CTN 0028, 0029) • One = Nicotine Patches (CTN 0009)

• One = Buproprion (CTN 0046)

* CTN 0048 Cocaine Use Reduction using buprenorphine (CURB)

Agonist Replacement for Opioid Dependence

• Methadone has been around 50+ years

• Treatment for heroin addiction in specialized treatment programs

• 1200 licensed OTP in the US with 260,000 MMT

• CTP and patients struggle with stigma

• There were few tools in the treatment box for opiate addiction: naltrexone – effective/poor acceptance LAAM - euthanized

Cont’d

• In non-methadone settings clonidine was (and still is) frequently used together with symptomatic specific meds; results were poor

• Anticipating approval of buprenorphine for treatment of opioid dependence the CTN launched two early, pre-approval, trials comparing suboxone to clonidine for short-term detox in outpatient and inpatient settings

• Prior to the early CTN 0001,0002, 0003 trials CTP pragmatic knowledge/understanding of buprenorphine was negligible.

• Early studies and then later 0010, 0027, 0030 helped shape best-practices guidelines for buprenorphine. Help educated staff and community. Help create a viable treatment addition to the options for opiate addiction.

“Detoxification is good for many things, getting off drugs is not one

of them”

(Walter Ling)

Suboxone

CTN 0001, 0002, 0003, 0010, 0027, 0030

CTN Studies with Suboxone• CTN 0001, 0002, 0003: short-term treatment

• CTN 0010: adolescent and young adult population

• CTN 0027: hepatic safety study (START)

• CTN 0030: specific to prescription opiates

Really the first opportunity for many CTP to gain some pragmatic experience with buprenorphine, also gave patients a similar benefit

First time buprenorphine used in adolescent/young adult population

For CTP the value of such opportunities with new treatments/technologies cannot be underestimated

CTP Experience with Suboxone Trials

• Six CTN trials utilizing Suboxone• Variety of programs participated• Many had little or no experience with

suboxone• Some had little or no experience with

research• All had some medical staff• Ranged from brief (13 day) to longer (8

months) exposure to buprenorphine

Cont’d

• Early buprenorphine/medications trials helped to confirm the CTN model: it was feasible to conduct medications trials in community-based treatment programs, retain scientific rigor maintaining fidelity

• Confirmed the value and utility of bi-directionality: pragmatic and hybrid protocols in real world settings

• Afforded an invaluable opportunity for exposure to a new treatment option and build a skill set to help optimize it’s use

• Driving change in treatment

• Developing tension can be seen: specialized treatment providers/private office-based treatment

To date there have been 2,946 patients randomized in six medication

trials with suboxone

Of these 2,404 had opportunity to receive suboxone

START at BAART

• Fairly typical of the programs participating in START

• Very busy Opioid Treatment Program: – 700+ MMT

• Well known and established in community (SF) 30 yrs

• Staffing included: physicians/extenders medical assistants, counselors, dispensary nurses, (research assistants)

• Began START 6/2006 – completed recruitment 10/09

START at BAART

• We had turnover of research staff including physicians

• We “relocated” the entire clinic during the study!

• When START rolled out the majority of study participants were only interested in methadone

• By the end a significant number of new participants were hoping to receiving suboxone

• We have learned much and this will be of practical use

Smoking• High prevalence of smoking behavior in SUD populations

• Only one completed study on smoking completed thus far (0009) MMT and Psychosocial CTP

Difficulty in recruitment/retention No difference at 3 and 6 mo follow-up Use of behavioral and nicotine replacement therapy

• Nevertheless, this was an important study in my opinion: First CTN trial for smoking

Included MMT and Psychosocial programs Pragmatic study which reflected realities of treatment

• New smoking medication trial (0046 - Winhusen) using buproprion for a specific subset of substance abusers

Medication Assisted Treatmentis being more widely adopted partially

as a result of CTN research

CTP who had previously generally not used agonist replacement treatment began slowly

incorporating suboxone:

Betty Ford CenterMaryhaven

others

CTP Issues

• CTP are very busy places• Not all CTP are staffed to participate in

medication research• Program “philosophy” may not always

embrace the use of medication-assisted treatment

• Critical to integrate research staff• Space• Priorities

What is important to CTP

• Treatment accessibility that meets need/demand

• Treatment retention• Acceptance of treatment by patients• Reduction of stigma • Sustaining treatment programs in tough times

• Retaining staff including research staff *• Dissemination of new treatment/knowledge• Funding• Regulatory consistency

What’s important to patients:

Quality of Life

Positive Outcomes

Exposure to new knowledge and skills

Possible new treatment interventions/options

Increased Accessibility to Treatment

Funding

Collegial support/Mentoring

Community Education

Bi-directional: invested in the protocol and research

Considerations for future medications research

The bi-directional opportunity the CTN affords is unique and should continue to shape research:

Co-occurring SUD and psychiatric disorders Co-occurring Alcohol Use Disorders* Adaptive/Sequential Models of Care** Stimulant abuse/dependence Chronic Pain and SUD Treatment Optimization Tapering/converting MMT to suboxone

-“crossover” Specific Populations – adolescents, aging, gender, prescription opioid dependence Longitudinal studies/longer follow-up

Cost-effectiveness and Cost-benefit analyses are useful to inform providers in making decisions regarding adoption

of new treatment

Adoption requires Sustainability

• Sustainability incorporates any number factors: Characteristics of medication is important to

adoption Cost-benefit Fit into program Consumer acceptance Timing Funding

Researchers/InvestigatorsProviders

*Provider-researchers

(something more than treatment providers who allow researchers to conduct studies within their programs)

This is an outcome of CTN bi-directionality, providers who are actively engaged in

research work with research mentor/colleagues, who enjoy and are invested

in the research as they are in treatment

Legacy of pharmacotherapy trials in CTP

• Medication-assisted treatment options are gaining wider acceptance among treatment providers and funding sources

• Buprenorphine has gained broader acceptance by providers and patients

• Benefits of participation easily justify the effort

• CTP make excellent locations for “pragmatic or hybrid model” clinical trials

• Combined medication assisted and behavioral treatment models offer powerful tools which can help drive change in treatment

Research drives treatment

Treatment drives research

Pharmacotherapy “Special Interest Group”

• Comprised largely of investigators and physicians, NIDA representatives and a few of us CTP folks

• Current Chair – Kathleen Brady, MD

• Discuss possible pharmacotherapy studies, medications in various stages of development and concept design for CTN protocols

• I have found participation very satisfying and a great learning experience

Just a few personal thoughts…

The moment that I realized what I wanted to do in life!

35 years ago I met….

Walter Ling

What a great ride!

• Ten years of bi-directional research • New Director of NIDA and NIH• 8 NIDA Blending Meetings• “All Hands Big Hug” and 9/11• Snipers – Pooks Hill

• Blizzards, Volcanoes• Made many friends• Lost some friends: Eileen Pencer, Len Handelsman,

Patrick McAuliffe

Sepulveda VA HospitalCirca 1977

It has been a great ten years, we look forward to the future…