Medication-Assisted Therapies for Opioid Use Disorder

(ExMAT CA Trial)

Recruiting at 4 trial locations

Overseen By Frederick L Altice, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Must be taking: Opioid agonist therapies

Disqualifiers: Not willing to provide consent

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

900 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore a new strategy to assist people with opioid use disorder in Central Asia. It focuses on improving access to opioid agonist therapies (OAT), which reduce cravings and withdrawal symptoms. The goal is to prevent new HIV infections in people who inject drugs by combining OAT with HIV treatments. Suitable candidates for this trial include those diagnosed with opioid dependence who are either new to OAT or have been on it for less than 90 days. As an unphased trial, this study offers participants the chance to contribute to innovative research that could enhance treatment strategies for opioid use disorder and HIV prevention.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It focuses on opioid agonist therapies, so it's best to discuss your current medications with the trial coordinators.

What prior data suggests that this implementation strategy is safe for scaling up opioid agonist therapies?

Past studies have shown that buprenorphine, a medication commonly used to treat opioid addiction, is safe and well-tolerated even at doses higher than 16 mg. This evidence comes from research involving individuals with opioid addiction in emergency room settings. The medication reduces cravings and improves the quality of life for those dealing with addiction. Although buprenorphine is generally safe, individuals should consider their personal needs and consult healthcare providers before deciding to join a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the NIATx model for opioid use disorder because it focuses on improving service delivery rather than introducing a new medication. Unlike standard treatments like methadone, buprenorphine, or naltrexone, which target brain chemistry to reduce cravings, NIATx enhances how existing treatments are implemented by providing coaching to optimize access and retention. This approach aims to streamline processes and remove barriers, potentially leading to better outcomes for individuals seeking help. By focusing on the efficiency of treatment delivery, NIATx has the potential to make current therapies more effective and accessible.

What evidence suggests that the NIATx model is effective for scaling up opioid agonist therapies in Central Asia?

Research has shown that medications like methadone, buprenorphine, and naltrexone can reduce opioid use and improve health. Studies have found that these medications help people stay in treatment longer, reduce cravings, and lower risky drug use. For example, methadone improves treatment retention, meaning people are more likely to stick with the program and have a better chance at recovery. In this trial, the NIATx model aims to make it easier for clinics to use these effective treatments and expand them in areas like Central Asia. ^{2 3 4 6 7}

Who Is on the Research Team?

Frederick L Altice, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults with opioid dependence in Central Asia, specifically those who inject drugs and are either new to opioid agonist therapy (OAT) or have been on OAT for less than 90 days. It includes both individuals seeking treatment and professionals involved in delivering OAT.

Inclusion Criteria

I am 18 or older with opioid dependence, new to treatment or on treatment for less than 90 days.

I am over 18 and a Chief Narcologist at an Oblast level.

I am over 18 and work in opioid addiction treatment.

Exclusion Criteria

Not willing to provide consent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Exploration/Preparation

Assess barriers and facilitators to OAT scale-up, including inner and outer context and bridging factors associated with OAT innovations

6 months

Implementation

Training in-country coaches and using a menu of tools and quality improvement techniques to scale-up OAT

12 months

Sustainment

Convene stakeholder meetings to guide implementation and inform policies for expanding OAT

18 months

Follow-up

Participants are monitored for sustainability and effectiveness of OAT scale-up

6 months

What Are the Treatments Tested in This Trial?

Interventions

• NIATx

Trial Overview The study tests the NIATx strategy, aiming to expand OAT programs effectively across Kazakhstan, Kyrgyzstan, and Tajikistan. The goal is to prevent HIV among people who inject drugs by improving addiction treatments using the EPIS framework.

How Is the Trial Designed?

Group I: NIATx Model Experimental Treatment 1 Intervention

Receiving NIATx Coaching

NIATx is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Subutex for:

• Opioid dependence
• Chronic pain

Approved in United States as Suboxone for:

• Opioid dependence

Approved in Canada as Temgesic for:

• Chronic pain
• Opioid dependence

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Den Sooluk Nuru

Collaborator

Trials

1

Recruited

900+

Global Health Research Center of Central Asia

Collaborator

Trials

1

Recruited

900+

AIDS Foundation East-West (AFEW) Kyrgyzstan

Collaborator

Trials

1

Recruited

900+

Institute for International Health and Education

Collaborator

Trials

1

Recruited

900+

Columbia University Global Health Research Center of Central Asia

Collaborator

Trials

1

Recruited

900+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

Buprenorphine (Subutex) was introduced as a legal treatment for opioid addiction following the Drug Addiction Treatment Act of 2000, allowing physicians to prescribe it for the first time in 80 years.

Despite its availability, only 12% to 15% of individuals with opioid dependence are enrolled in methadone maintenance programs, highlighting significant barriers to treatment access and care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anesthesia for patients on buprenorphine. Bryson, EO., Lipson, S., Gevirtz, C.[2013]

Buprenorphine is a safe and effective treatment for opioid dependence, particularly when combined with naloxone, which reduces its potential for abuse.

New regulations enable certified physicians to prescribe buprenorphine in their offices, significantly improving patient access to this important treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine maintenance: a new treatment for opioid dependence. Collins, GB., McAllister, MS.[2019]

Buprenorphine, a partial mu-opioid receptor agonist, is an effective and well-tolerated treatment for opioid dependence, comparable to methadone, and can now be prescribed by all physicians in office-based settings due to the Drug Addiction Treatment Act of 2000.

It is available in two formulations: Subutex (buprenorphine only) and Suboxone (buprenorphine with naloxone), but physicians must obtain a special waiver to prescribe it and are limited to 30 patients at a time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine: a (relatively) new treatment for opioid dependence. Welsh, C., Valadez-Meltzer, A.[2021]

Parenteral abuse of Subutex, a medication for opioid dependency, has led to severe complications in patients, including vascular issues and nerve injuries, with all four reported cases resulting in poor outcomes.

Despite various treatments, such as surgery and medication, patients experienced significant impairments, including amputations and ongoing pain, highlighting the urgent need for preventive measures through education and legal actions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe upper limb complications from parenteral abuse of Subutex. Loo, HW., Yam, AK., Tan, TC., et al.[2020]

The RDD study, one of the largest clinical trials for opioid use disorder (OUD), will evaluate different dosing strategies of buprenorphine and the impact of a digital therapeutic app on treatment retention, addressing the significant issue of poor retention rates in current OUD treatments.

The trial will also explore tapering strategies for buprenorphine in patients in stable remission, aiming to identify effective methods for safely discontinuing medication while minimizing relapse, which is crucial for long-term recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prior National Drug Abuse Treatment Clinical Trials Network (CTN) opioid use disorder trials as background and rationale for NIDA CTN-0100 "optimizing retention, duration and discontinuation strategies for opioid use disorder pharmacotherapy (RDD)". Shulman, M., Weiss, R., Rotrosen, J., et al.[2021]

The Drug Abuse Treatment Act of 2000 (DATA) expanded treatment options for opioid addiction by allowing certified physicians to prescribe buprenorphine in office settings, increasing access to care.

Clinical studies show that buprenorphine is as effective as methadone for maintaining treatment and reducing illicit opioid use, and it is more effective than clonidine for short-term detoxification, highlighting its role as a valuable tool in addiction treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupreorphine:a new pharmacotherapy for opioid addictions treatment. Stock, C., Shum, JH.[2013]

Buprenorphine (Subutex) is recognized for its improved safety profile in treating opioid dependence, particularly by reducing the risk of overdose compared to other opioids.

Despite its safety advantages, there are still risks associated with the diversion of buprenorphine for misuse, as evidenced by cases of attempted intravenous injection, highlighting the need for strict dispensing protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Groin tissue necrosis requiring skin graft following parenteral abuse of buprenorphine tablets. Feeney, GF., Fairweather, P.[2013]

Nicotine replacement therapies are the most effective option for helping people quit smoking, while naltrexone, acamprosate, and disulfiram are effective in reducing alcohol consumption.

For opiate use disorders, agonist therapies like methadone and buprenorphine are the most effective treatments, highlighting the importance of combining medication with behavioral therapies for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medications for substance use disorders. Douaihy, AB., Kelly, TM., Sullivan, C.[2021]

The FDA-approved extended-release formulation of naltrexone, administered as a monthly injection, may improve adherence and retention rates in treating opioid dependence compared to the oral form, which has low compliance (less than 30%).

While naltrexone effectively reduces the rewarding effects of opioids to prevent relapse, there are safety concerns, including potential liver damage at high doses and risks of opioid overdose if individuals attempt to overcome the drug's antagonistic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone extended-release injection: an option for the management of opioid abuse. Taylor, R., Raffa, RB., Pergolizzi, JV.[2021]

Buprenorphine and buprenorphine/naloxone (Subutex, Suboxone) are effective treatments for opioid dependence, showing similar efficacy to methadone in retaining patients in treatment and reducing illicit opioid use, as supported by clinical studies.

Despite their effectiveness, there are concerns about the long-term effects and potential toxicity of buprenorphine, particularly regarding its mechanism of action that may lead to anti-reward effects and increased relapse potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can the chronic administration of the combination of buprenorphine and naloxone block dopaminergic activity causing anti-reward and relapse potential? Blum, K., Chen, TJ., Bailey, J., et al.[2021]

A study is being conducted to evaluate the effectiveness of the smartphone app OptiMAT as an adjunctive intervention for improving outcomes in medication-assisted treatment (MAT) for opioid use disorder (OUD), particularly among adults in outpatient settings.

The trial will compare opioid misuse rates between participants using OptiMAT alongside their treatment and those receiving standard treatment alone, with results expected to inform future use of the app in rural areas and identify which features of OptiMAT are most beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Smartphone intervention to optimize medication assisted treatment outcomes for opioid use disorder: study protocol for a randomized controlled trial. Thompson, RG., Bollinger, M., Mancino, M., et al.[2023]

After three years of buprenorphine's approval for office-based treatment of opioid addiction, nearly 90% of addiction specialists were authorized to prescribe it, with two-thirds actively treating patients, indicating strong adoption among specialists.

In contrast, fewer than 10% of non-addiction specialist psychiatrists prescribed buprenorphine, highlighting a significant gap in treatment access and suggesting that organizational support and training are crucial for expanding its use beyond addiction specialists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of buprenorphine for addiction treatment: perspectives of addiction specialists and general psychiatrists. Thomas, CP., Reif, S., Haq, S., et al.[2021]

A study is being conducted to evaluate the effectiveness of a smartphone app called OptiMAT as an adjunctive intervention for improving outcomes in medication-assisted treatment (MAT) for opioid use disorder (OUD), specifically targeting individuals in outpatient settings.

The trial will compare two groups: one receiving standard MAT and the other receiving MAT with the OptiMAT app, assessing opioid misuse through urinalysis over a 6-month period, which could lead to better treatment strategies in rural areas heavily affected by the opioid crisis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Smartphone intervention to optimize medication-assisted treatment outcomes for opioid use disorder: study protocol for a randomized controlled trial. Thompson, RG., Bollinger, M., Mancino, MJ., et al.[2023]

Citations

1. nida.nih.gov nida.nih.gov/research-topics/medications-opioid-use-disorder

Medications for Opioid Use Disorder Research has shown that methadone, buprenorphine, and naltrexone can reduce opioid use and other negative health outcomes. For example ...

2. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2825088

Buprenorphine/Naloxone vs Methadone for the Treatment ... The risk of treatment discontinuation was higher among recipients of buprenorphine/naloxone compared with methadone (88.8% vs 81.5% within 24 months).

3. sciencedirect.com sciencedirect.com/science/article/pii/S2772724623000033

History of the discovery, development, and FDA-approval ... Outcomes in the 8 mg group were significantly better than in the 1 mg group on the four domains of retention in treatment, illicit opioid use, opioid craving, ...

4. cdc.gov cdc.gov/mmwr/volumes/73/wr/mm7325a1.htm

Treatment for Opioid Use Disorder: Population Estimates In 2022, 3.7% of US adults aged ≥18 years needed OUD treatment. Among these, only 25.1% received medications for OUD.

5. acog.org acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/08/opioid-use-and-opioid-use-disorder-in-pregnancy

Opioid Use and Opioid Use Disorder in Pregnancy More research is needed to assess the safety (particularly regarding maternal relapse), efficacy, and long-term outcomes of medically supervised withdrawal.

6. nih.gov nih.gov/news-events/news-releases/higher-doses-buprenorphine-may-improve-treatment-outcomes-people-opioid-use-disorder

Higher doses of buprenorphine may improve treatment ... Studies have shown that more than 16 mg of buprenorphine is safe and well tolerated in people with opioid use disorder in emergency department ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK459126/

Buprenorphine - StatPearls - NCBI Bookshelf The drug proves to be an effective choice for addressing opioid dependence by diminishing cravings and enhancing the overall quality of life during addiction ...