Engagement Strategies for Alcoholism Treatment

(ENHANCE Trial)

Overseen By Yudilyn Jaramillo, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Must be taking: MAUD

Disqualifiers: Opioid use disorder, Pregnancy, others

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

Compensation: Varies

Number of Visits: 34

Duration: 34 days

450 Participants Needed

Trial Summary

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 might be best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment BNI+facilitated provision of MAUD, Naltrexone, Acamprosate, Disulfiram, Vivitrol, Campral, Antabuse, BNI+facilitated provision of MAUD+CBT4CBT, ReVia, Vivitrol, Naltrexone Hydrochloride, Brief Negotiated Interview (BNI), Brief Negotiated Interview, BNI for alcoholism?

Research shows that naltrexone and acamprosate can help reduce alcohol consumption, and disulfiram (Antabuse) can support abstinence by causing unpleasant effects when alcohol is consumed. Behavioral therapies like the Brief Negotiated Interview (BNI) and cognitive-behavioral therapy (CBT) can enhance treatment adherence and effectiveness. ^{1 2 3 4 5}

Is the treatment for alcoholism using medications like Naltrexone, Acamprosate, and Disulfiram generally safe for humans?

Naltrexone, Acamprosate, and Disulfiram are FDA-approved medications for treating alcohol dependence, indicating they have been evaluated for safety in humans. These medications are considered part of high-quality care for alcohol use disorder, suggesting they are generally safe when used as directed. ^{3 6 7 8 9}

How is the treatment BNI+facilitated provision of MAUD+CBT4CBT different from other treatments for alcoholism?

This treatment is unique because it combines medication-assisted treatment (using drugs like naltrexone, acamprosate, and disulfiram) with a Brief Negotiated Interview (BNI) and cognitive-behavioral therapy (CBT4CBT), which is a digital form of therapy. This approach not only targets the brain's reward system with medication but also provides structured counseling and digital therapy to support behavior change, making it a comprehensive strategy for treating alcoholism. ^{3 6 7 9 10}

What is the purpose of this trial?

This study is a 3-arm randomized clinical trial to evaluate the effectiveness of hospital-initiated Alcohol Use Disorder treatment, involving a Brief Negotiated Interview (with referral and telephone booster) alone, BNI+facilitated provision of MAUD, BNI+facilitated provision of MAUD+CBT4CBT on AUD treatment engagement, alcohol use and healthcare utilization.

Research Team

E. Jennifer Edelman, MD

Principal Investigator

Yale University

Brian Kiluk, PhD

Principal Investigator

Yale University

Eligibility Criteria

This trial is for adults at Yale New Haven Hospital who've had a heavy drinking day in the past month, can consent to follow-ups, and have moderate to severe Alcohol Use Disorder. It's not for those recently in AUD treatment, pregnant/nursing women, or with life-threatening conditions that hinder participation.

Inclusion Criteria

I am open to considering medical aid in dying.

Provide written informed consent

Willing and able to be contacted for follow-up

Exclusion Criteria

Anticipate being unable to return for follow-up assessments for any reason, such as travel, incarceration, planned procedure

Meet DSM-5 criteria for untreated moderate to severe opioid use disorder

I do not have any severe health or mental conditions that prevent me from joining the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive hospital-initiated Alcohol Use Disorder treatment, involving a Brief Negotiated Interview (BNI) with referral and telephone booster, with or without facilitated provision of MAUD and CBT4CBT

34 days

In-hospital initiation with follow-up telephone booster

Follow-up

Participants are monitored for AUD treatment engagement, alcohol use, and healthcare utilization at 34 and 90 days post-discharge

90 days

Assessments at 34 and 90 days post-discharge

Treatment Details

Interventions

• BNI+facilitated provision of MAUD
• BNI+facilitated provision of MAUD+CBT4CBT
• Brief Negotiated Interview (BNI)

Trial Overview The study tests three treatments post-hospitalization: Brief Negotiated Interview (BNI), BNI plus Medication-Assisted Treatment (MAUD), and BNI+MAUD combined with computer-based Cognitive Behavioral Therapy (CBT4CBT) to see which helps more with alcohol use reduction.

Participant Groups

Group I: Brief Negotiated Interview (with referral and telephone booster) alone Experimental Treatment 1 Intervention

All participants will receive BNI with referral and a 15-20 minute telephone booster delivered by a trained Health Promotion Advocate (HPA) at 2 weeks. The purpose of the BNI is to assist patients in recognizing and changing levels of alcohol consumption that pose health risks. The main goals of the BNI are to: 1) lessen ambivalence about reducing alcohol use; and 2) negotiate strategies for change. During BNI, the HPA will: 1) Raise the subject of alcohol; 2) Provide feedback: review the patient's alcohol consumption, make a connection to the patient's medical condition and reason for hospitalization; review guidelines for lower risk alcohol use; 3) Enhance motivation: have the patient identify on a readiness change ruler and develop discrepancy; and 4) Negotiate and Advise: negotiate goal, give advice, have patient complete drinking agreement; summarize and arrange follow-up.

Group II: BNI+MAUD+CBT4CBT Experimental Treatment 1 Intervention

Participants randomized to BNI+facilitated provision of MAUD+CBT4CBT will be given a username and password to access the web-based program and be encouraged to begin accessing the program during their hospitalization. The HPA will assist each participant with login during the first session and be available to answer any questions. Participants will be asked to complete no more than two modules per week, with an expectation of completing all seven modules by the end of the 34-day post-discharge. The program tracks, for each participant, time logged onto the program, modules accessed, progress through the program from session to session, completion of homework assignments, and learning of CBT principles through brief quizzes. Participants will be allowed to repeat modules as desired. During the BNI telephone booster, the HPA will inquire about engagement with CBT4CBT, address any questions and problems with the program, and encourage practice of coping activities (i.e., homework).

Group III: BNI+MAUD Active Control 1 Intervention

For either BNI+facilitated provision of MAUD or BNI+facilitated provision of MAUD+CBT4CBT, the HPA will provide education and counseling regarding MAUD as part of the BNI to the participant and communicate to the primary medical team that MAUD is indicated. The specific MAUD chosen will be made at the discretion of the patient and the primary medical team with recommendations from the study physicians, with a goal of prioritizing FDA approved medications. Participants will be encouraged to initiate (or receive as in the case of injectable naltrexone) MAUD prior to discharge and will be provided a prescription for a 30-day supply. Medications will be obtained through regular means and not provided directly through the study. During the BNI telephone booster, the HPA will inquire about and address any barriers to MAUD and encourage continued adherence.

BNI+facilitated provision of MAUD is already approved in United States, European Union for the following indications:

Approved in United States as MAUD for:

• Alcohol Use Disorder

Approved in European Union as MAUD for:

• Alcohol Dependence

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Findings from Research

Behavioral naltrexone therapy (BNT) was tested in a pilot trial with 47 participants, showing that individuals with higher dependence on opiates, particularly methadone and heroin, had shorter retention in treatment.

The study suggests that those with greater physiological dependence may need more gradual detoxification and intensive behavioral support to improve compliance with naltrexone maintenance therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of retention in naltrexone maintenance for opioid dependence: analysis of a stage I trial. Sullivan, MA., Rothenberg, JL., Vosburg, SK., et al.[2016]

Behavioral Naltrexone Therapy (BNT) was designed to improve adherence to naltrexone treatment for opiate dependence by using strategies like Network Therapy and voucher incentives, but retention rates were low overall, with only 19% of participants completing the 6-month treatment in an uncontrolled trial of 47 subjects.

Retention was particularly challenging for patients using methadone, with none completing the full 6 months, while heroin-dependent patients showed better outcomes, with 31% completing the treatment, highlighting the need for tailored interventions to improve compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Behavioral naltrexone therapy: an integrated treatment for opiate dependence. Rothenberg, JL., Sullivan, MA., Church, SH., et al.[2019]

In a study involving 223 substance use disorder treatment program administrators over 48 months, it was found that while most programs did not adopt disulfiram or tablet naltrexone for alcohol use disorders, about 20% sustained their use, indicating some level of effectiveness in certain settings.

Factors such as being hospital-based, program size, and having accreditation were linked to the sustained use of these medications, suggesting that organizational support and resources play a crucial role in the adoption and continuation of alcohol use disorder treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A longitudinal examination of alcohol pharmacotherapy adoption in substance use disorder treatment programs: patterns of sustainability and discontinuation. Abraham, AJ., Knudsen, HK., Roman, PM.[2022]

The COMBINE study identified five drinking trajectories among participants prior to treatment, revealing that those with 'nearly daily' and 'consistent daily' drinking patterns had worse outcomes compared to 'frequent drinkers' during treatment.

Acamprosate was effective in increasing abstinence chances for 'very frequent drinkers', but surprisingly decreased abstinence rates for 'daily drinkers stopping early', indicating that treatment responses can vary significantly based on prior drinking patterns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline trajectories of drinking moderate acamprosate and naltrexone effects in the COMBINE study. Gueorguieva, R., Wu, R., Donovan, D., et al.[2021]

In a study of 243 alcohol-dependent patients over 2.5 years, disulfiram (DIS) was found to be more effective than naltrexone (NTX) and acamprosate (ACA) in reducing heavy drinking days and increasing abstinent days during the initial 12-week medication phase.

While all three medications combined with cognitive-behavioral therapy led to reduced alcohol consumption and improved quality of life, DIS showed superior results in maintaining abstinence compared to ACA and NTX during the follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, multicentre, open-label, comparative trial of disulfiram, naltrexone and acamprosate in the treatment of alcohol dependence. Laaksonen, E., Koski-Jännes, A., Salaspuro, M., et al.[2018]

Recent advancements in understanding the neurobiology of alcohol disorders have led to the development of four FDA-approved medications for alcohol dependence, which significantly enhance treatment outcomes compared to traditional counseling alone.

The approved medications include disulfiram, oral naltrexone, acamprosate, and an extended-release injectable form of naltrexone, with ongoing research exploring additional options like topiramate and quetiapine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Choosing the right medication for the treatment of alcoholism. Pettinati, HM., Rabinowitz, AR.[2022]

High prescribers of medications for alcohol use disorder (AUD) demonstrated a more favorable view of the effectiveness of these medications compared to low prescribers, indicating that attitudes towards treatment efficacy can influence prescribing behavior.

PCPs with positive attitudes towards AUD treatment had a significantly higher prescribing rate (5.0%) compared to those with negative attitudes (1.9%), suggesting that improving attitudes may be crucial for increasing the use of medications like acamprosate, naltrexone, and disulfiram.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship Between Primary Care Providers' Perceptions of Alcohol Use Disorder And Pharmacotherapy Prescribing Rates. Bernstein, EY., Pfoh, ER., Le, P., et al.[2023]

Among women veterans diagnosed with alcohol use disorder (AUD), those involved in the criminal justice system had higher odds (29% more likely) of receiving pharmacotherapy for AUD compared to those without justice involvement, indicating that legal mandates and supportive programs may facilitate access to treatment.

Despite the overall increase in pharmacotherapy receipt among women veterans from 14% to 21% between 2014 and 2017, older women (55+) and African-American veterans had lower odds of receiving treatment, highlighting disparities in access to AUD pharmacotherapy within this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Receipt of pharmacotherapy for alcohol use disorder by justice-involved women in the Veterans Health Administration. Taylor, E., Timko, C., Harris, AHS., et al.[2021]

In a study of over 250,000 Veterans Health Administration patients with alcohol use disorder, the initiation rates of medications like acamprosate, naltrexone, and disulfiram only slightly increased from 2.8% in 2006 to 3.0% in 2007, indicating low overall uptake of these approved treatments.

Patients receiving specialty addiction care, particularly those under 55 years and females, were more likely to receive these medications, highlighting the need for improved access and understanding of treatment options across different facilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy of alcohol use disorders in the Veterans Health Administration. Harris, AH., Kivlahan, DR., Bowe, T., et al.[2022]

A home-based contracting program significantly improved compliance rates among 25 discharged alcohol patients taking disulfiram, with those in the contracting groups showing better adherence than those with no contract.

At the 3-month follow-up, 84% of participants reported abstinence from alcohol, suggesting that this low-cost intervention could be an effective alternative to more expensive treatment programs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spouse contracting to increase antabuse compliance in alcoholic veterans. Keane, TM., Foy, DW., Nunn, B., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Predictors of retention in naltrexone maintenance for opioid dependence: analysis of a stage I trial. [2016]

2. United States pubmed.ncbi.nlm.nih.gov

Behavioral naltrexone therapy: an integrated treatment for opiate dependence. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

A longitudinal examination of alcohol pharmacotherapy adoption in substance use disorder treatment programs: patterns of sustainability and discontinuation. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Baseline trajectories of drinking moderate acamprosate and naltrexone effects in the COMBINE study. [2021]

5. England pubmed.ncbi.nlm.nih.gov

A randomized, multicentre, open-label, comparative trial of disulfiram, naltrexone and acamprosate in the treatment of alcohol dependence. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Choosing the right medication for the treatment of alcoholism. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Relationship Between Primary Care Providers' Perceptions of Alcohol Use Disorder And Pharmacotherapy Prescribing Rates. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Receipt of pharmacotherapy for alcohol use disorder by justice-involved women in the Veterans Health Administration. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Pharmacotherapy of alcohol use disorders in the Veterans Health Administration. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Spouse contracting to increase antabuse compliance in alcoholic veterans. [2019]