ED-Initiated Naltrexone + Gabapentin for Alcoholism

Overseen By Kathryn Hawk, MD, MHS

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Yale University

Must not be taking: Opioids, Gabapentin, Naltrexone

Disqualifiers: OUD, Cognitive impairment, Psychosis, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

240 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to assist individuals with moderate to severe alcohol use disorder (AUD) directly from the emergency department (ED). It combines a brief conversation about alcohol use with a referral to ongoing treatment, using medications like naltrexone (available as an injection or pill) and gabapentin (a pill), which may help reduce heavy drinking days. The goal is to determine if this combination encourages more people to remain engaged in treatment 30 days after their ED visit. This approach suits those who struggle with AUD and are open to starting treatment in the ED. As a Phase 3 trial, this treatment represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking solution for AUD.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently taking gabapentin or naltrexone, or if you have been treated with medications for alcohol use disorder in the past week.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that naltrexone, available as a pill or injection, is generally safe for treating alcohol use disorder. The FDA has approved it, confirming its safety for this purpose. Some people might experience side effects like nausea or headaches, but most handle these well.

Gabapentin has also undergone research for alcohol use disorder. It is considered safe and usually well-tolerated. Studies indicate it can help with withdrawal symptoms, such as cravings and anxiety, with few side effects.

Overall, both naltrexone and gabapentin have a strong safety record for treating alcohol use disorder. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for alcoholism because they combine medications in a unique way to enhance effectiveness. Unlike the standard care options, which typically involve counseling and medications like disulfiram or acamprosate, this approach uses naltrexone, available both as an injection and a pill, alongside gabapentin. This combination not only targets cravings more effectively but also uses a new delivery method with the naltrexone injection, potentially making treatment easier for patients. Additionally, the Brief Negotiation Interview component aims to motivate patients during their emergency department visits, linking immediate care with long-term treatment goals. This innovative approach could lead to more immediate and sustained recovery outcomes.

What evidence suggests that this trial's treatments could be effective for alcohol use disorder?

Research shows that naltrexone, available as a shot or a pill, effectively treats alcohol use disorder (AUD). It reduces the number of heavy drinking days and supports sobriety in many cases. Studies have found that taking a 50 mg naltrexone pill daily is a recommended treatment for AUD. In this trial, participants in the SBIRT+ED-MAUD arm will receive either an injection or oral form of naltrexone, supplemented by gabapentin.

Gabapentin has also been shown to help people with AUD by reducing cravings and supporting sobriety. It can improve sleep and lessen the urge to drink alcohol. Together, naltrexone and gabapentin may provide a strong approach for those looking to cut down on alcohol and improve their recovery. Participants in the SBIRT+ED-MAUD arm will receive their first doses of gabapentin in the ED, with additional take-home doses to support their treatment. ^{1 2 5 6 7}

Who Is on the Research Team?

Kathryn Hawk, MD, MHS

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with moderate to severe Alcohol Use Disorder not in remission. Participants must be willing and able to follow the study procedures, available for its duration, and speak English well enough to understand it. Women of childbearing age must test negative for pregnancy and agree to effective birth control during the study.

Inclusion Criteria

Diagnosed with moderate to severe Alcohol Use Disorder

Clinical Alcohol Withdrawal Scale (CIWA-Ar) ≥ 4

Reproductive aged females will have a negative pregnancy test within the past 24 hours and agree to use of highly effective family planning during study participation period

Exclusion Criteria

My kidney function test shows reduced creatinine clearance.

Currently pregnant or breast feeding

History of complicated alcohol withdrawal

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive ED-initiated medications for alcohol use disorder, including naltrexone and gabapentin, with a brief intervention and referral to ongoing treatment

4 weeks

1 visit (in-person), daily medication adherence monitoring

Follow-up

Participants are monitored for safety and effectiveness, including treatment engagement and reduction in heavy drinking days

4 weeks

1 visit (in-person), self-reported outcomes

Extension

Participants may continue to receive support and monitoring for ongoing AUD treatment engagement

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Brief Negotiation Interview
• Gabapentin Pill
• Naltrexone Injection
• Naltrexone Pill

Trial Overview The trial tests if starting medications (Naltrexone Pill or Injection, Gabapentin Pill) in the emergency department helps people with alcohol use disorder engage better in treatment after 30 days compared to just a brief intervention and referral. It's a phase 3 study where participants are randomly assigned treatments.

How Is the Trial Designed?

Group I: SBIRT+ED-MAUD Experimental Treatment 4 Interventions

Participants with receive BNI, Referral to Treatment, and MAUD. In the MAUD component, either XR-NTX or oral naltrexone will be provided, supplemented by ancillary treatment with gabapentin. Participants will receive their first doses of XR-NTX (injection) and gabapentin in the ED and will receive 7 days of gabapentin take-home doses. Those who prefer to initiate treatment in ED with oral naltrexone receive their first doses of naltrexone and gabapentin in the ED and receive 29-day take-home doses of naltrexone and 7 days of gabapentin.

Group II: SBIRT Experimental Treatment 1 Intervention

Participants will receive the Brief Negotiation Interview (BNI) and Referral to Treatment. The BNI has four key components: (1) permission to discuss substance use, (2) feedback on the health consequences of ongoing substance use, including making a connection between the ED visit and substance use, (3) motivational enhancement, and (4) negotiation and advice.

Brief Negotiation Interview is already approved in United States, European Union for the following indications:

Approved in United States as Campral for:

• Maintenance of abstinence from alcohol in patients with alcohol dependence

Approved in European Union as Acamprosate for:

• Maintenance of abstinence from alcohol in patients with 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+

Published Research Related to This Trial

In a study of 169 alcohol-dependent individuals over 12 weeks, naltrexone showed a significant benefit in preventing relapse for those with low levels of depression and alcohol dependence, while acamprosate did not demonstrate any efficacy.

Overall, there were no significant differences in drinking outcomes between naltrexone, acamprosate, and placebo, indicating that naltrexone may be more effective for specific subgroups rather than the general population of alcohol-dependent individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone versus acamprosate in the treatment of alcohol dependence: A multi-centre, randomized, double-blind, placebo-controlled trial. Morley, KC., Teesson, M., Reid, SC., et al.[2022]

In a study involving 24 healthy adult volunteers, the combination of acamprosate and naltrexone was found to enhance the absorption of acamprosate, leading to a 33% increase in its maximum plasma concentration without affecting naltrexone's pharmacokinetics.

The co-administration of these two medications showed no negative interactions on safety or cognitive function, suggesting that they can be safely used together in treating alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pharmacokinetic and pharmacodynamic drug interaction study of acamprosate and naltrexone. Mason, BJ., Goodman, AM., Dixon, RM., et al.[2018]

Acamprosate significantly improves abstinence rates and cumulative abstinence duration in individuals with alcohol dependence, making it particularly effective for achieving complete abstinence.

Naltrexone effectively reduces relapse rates in the short term but does not significantly increase abstinence rates; it is better suited for programs focused on controlled drinking. Both medications are generally safe and well-tolerated, but compliance remains a challenge.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of naltrexone and acamprosate in the treatment of alcohol dependence: a systematic review. Bouza, C., Angeles, M., Muñoz, A., et al.[2018]

In a study of 160 patients with alcoholism, both naltrexone and acamprosate were found to be significantly more effective than placebo in preventing relapse over a 12-week period.

The combination of naltrexone and acamprosate resulted in the lowest relapse rates compared to placebo and acamprosate alone, indicating that using both medications together enhances their effectiveness in relapse prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism: a double-blind, placebo-controlled study. Kiefer, F., Jahn, H., Tarnaske, T., et al.[2019]

Acamprosate and naltrexone are the only two medications approved for treating alcohol use disorders (AUDs) that have strong evidence from numerous clinical trials, making them effective options for patients.

Several off-label medications, such as topiramate and gabapentin, show promise for treating AUDs, but more research is needed to confirm their efficacy and safety in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy of alcoholism - an update on approved and off-label medications. Soyka, M., Müller, CA.[2018]

In a clinical trial with 150 alcohol-dependent individuals, combining gabapentin with naltrexone significantly improved drinking outcomes during the first 6 weeks of abstinence, leading to longer intervals before heavy drinking and fewer heavy drinking days compared to naltrexone alone.

The benefits of adding gabapentin diminished after the first 6 weeks, indicating that while it can help manage early abstinence symptoms, its effects do not persist once treatment is stopped.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gabapentin combined with naltrexone for the treatment of alcohol dependence. Anton, RF., Myrick, H., Wright, TM., et al.[2022]

Acamprosate, an oral medication for alcohol dependence, has been shown to effectively restore normal glutamatergic neurotransmission disrupted by chronic alcohol use, making it a valuable treatment option.

The drug has an excellent safety profile and has been validated through multiple Phase I, II, and III clinical trials, indicating its suitability for a wide range of alcohol-dependent patients when used alongside psychosocial interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The neurobiology, clinical efficacy and safety of acamprosate in the treatment of alcohol dependence. Mason, BJ., Heyser, CJ.[2018]

Acamprosate and naltrexone, both effective in treating alcohol dependence, can be safely combined without significant adverse effects, as shown by pharmacokinetic studies that indicate increased acamprosate levels when used together.

The combination of these two medications may enhance clinical benefits, suggesting that further large-scale trials are warranted to explore their efficacy and safety in treating alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale for combining acamprosate and naltrexone for treating alcohol dependence. Mason, BJ.[2019]

Injectable formulations of naltrexone, such as Vivitrex/Vivitrol and Naltrel, show promise in treating alcohol dependence with potentially fewer side effects compared to oral naltrexone, which has limitations like a small treatment effect size and plasma level fluctuations.

Vivitrex/Vivitrol has been effective in reducing heavy drinking in alcohol-dependent males, while Naltrel has been shown to promote abstinence and reduce relapse rates, indicating that these depot formulations may offer improved therapeutic options for alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone long-acting formulation in the treatment of alcohol dependence. Johnson, BA.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7063541/

Efficacy of Gabapentin for the Treatment of Alcohol Use ... This study showed that gabapentin is efficacious in promoting abstinence and reducing drinking in individuals with alcohol use disorder.

2. psychiatrist.com psychiatrist.com/pcc/gabapentin-and-withdrawal-in-alcohol-use-disorder/

Effectiveness of Gabapentin in Reducing Cravings and ... Objective: The current meta-analysis synthesizes previous findings on the effect of gabapentin on alcohol withdrawal and craving.

3. jamanetwork.com jamanetwork.com/journals/jamainternalmedicine/fullarticle/1764009

Gabapentin Treatment for Alcohol Dependence Results Gabapentin significantly improved the rates of abstinence and no heavy drinking. The abstinence rate was 4.1% (95% CI, 1.1%-13.7%) in the placebo group, ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5957503/

Gabapentin for the treatment of alcohol use disorder - PMC Studies showing reduced drinking and decreased craving and alcohol-related disturbances in sleep and affect in the months following alcohol cessation suggest ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0091305722001617

Gabapentin increases the abuse liability of alcohol alone ... In patients with AUD, gabapentin 1200 mg/day appears effective in reducing alcohol consumption, improving sleep, and decreasing alcohol craving (Mason et al., ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2542454820301041

Retrospective Analysis of Gabapentin for Alcohol ... Available evidence suggests that gabapentin is associated with low rates of adverse effects and often improves withdrawal symptoms, including cravings, anxiety, ...

7. ccjm.org ccjm.org/content/86/12/815

Gabapentin for alcohol use disorder: A good option, or ... Gabapentin has been shown to be safe and effective for mild alcohol withdrawal but is not appropriate as mono-therapy for severe withdrawal ...