ED-Initiated Naltrexone + Gabapentin for Alcoholism
Recruiting in Palo Alto (17 mi)
Overseen byKathryn Hawk, MD, MHS
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Yale University
Must not be taking: Opioids, Gabapentin, Naltrexone
Disqualifiers: OUD, Cognitive impairment, Psychosis, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?The proposed study will be the first randomized clinical trial to evaluate a comprehensive Emergency Department (ED)-based intervention for moderate to severe Alcohol Use Disorder (AUD) combining Screening, Brief Intervention and Referral to Treatment (SBIRT) with ED-initiated medications for treatment of alcohol use disorder (MAUD).
The primary objective of this phase 3 study is to evaluate for differences in treatment engagement 30 days after ED visit between emergency department patients with moderate to severe alcohol use disorder (AUD) who are randomized to initiate medications for the treatment for AUD in the ED in addition to receiving a brief intervention and referral to ongoing treatment, which all participants will receive.
The secondary objective of this study is to evaluate the difference in reduction of heavy drinking days between the two ED treatment models during the 30 days post ED visit.
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.
What data supports the effectiveness of the drugs used in the ED-Initiated Naltrexone + Gabapentin for Alcoholism trial?
Research shows that naltrexone and acamprosate are effective drugs for treating alcohol dependence, with naltrexone being particularly effective in reducing alcohol cravings. Gabapentin may help with symptoms like insomnia and mood instability during early abstinence, potentially preventing early relapse.
12345Is the combination of naltrexone and gabapentin safe for treating alcohol dependence?
Naltrexone and acamprosate have been shown to be safe in treating alcohol dependence, with naltrexone's injectable form having fewer side effects than the oral form. Gabapentin, when combined with naltrexone, may help reduce symptoms like insomnia and mood instability during early abstinence, suggesting it is generally safe for this use.
12567How does the drug combination of naltrexone and gabapentin differ from other treatments for alcoholism?
This treatment is unique because it combines naltrexone, which helps reduce cravings for alcohol, with gabapentin, which may alleviate withdrawal symptoms like insomnia and mood instability, potentially preventing early relapse. This combination targets both the craving and withdrawal aspects of alcohol dependence, which might make it more effective than using naltrexone alone.
12389Eligibility Criteria
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
Clinical Alcohol Withdrawal Scale (CIWA-Ar) ≥ 4
I am between 18 and 80 years old.
Diagnosed with moderate to severe Alcohol Use Disorder
+3 more
Exclusion Criteria
Current diagnosis of OUD, self-reported past 7 day opioid or opioid pain medication use, or a positive urine opioid screen (opiates, methadone, buprenorphine, oxycodone, hydrocodone, tramadol and fentanyl)
In police custody
History of complicated alcohol withdrawal
+14 more
Trial Timeline
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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: SBIRT+ED-MAUDExperimental Treatment4 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: SBIRTExperimental Treatment1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Yale New Haven HospitalNew Haven, CT
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Who Is Running the Clinical Trial?
Yale UniversityLead Sponsor
National Institute on Alcohol Abuse and Alcoholism (NIAAA)Collaborator
References
Gabapentin combined with naltrexone for the treatment of alcohol dependence. [2022]Naltrexone, an efficacious medication for alcohol dependence, does not work for everyone. Symptoms such as insomnia and mood instability that are most evident during early abstinence might respond better to a different pharmacotherapy. Gabapentin may reduce these symptoms and help prevent early relapse. This clinical trial evaluated whether the combination of naltrexone and gabapentin was better than naltrexone alone and/or placebo during the early drinking cessation phase (first 6 weeks), and if so, whether this effect persisted.
Pharmacotherapy of alcoholism - an update on approved and off-label medications. [2018]Only a few medications are available for the treatment of alcohol use disorders (AUDs). Areas covered: This paper discusses approved AUD medications, including the opioid antagonists naltrexone and nalmefene (the latter is licensed for reduction of alcohol consumption only), the putative glutamate receptor antagonist acamprosate and the aldehyde dehydrogenase inhibitor disulfiram. It also covers off-label medications of interest, including topiramate, gabapentin, ondansetron, varenicline, baclofen, sodium oxybate and antidepressants. Clinical implications, benefits and risks of treatment are discussed. Expert opinion: Acamprosate, naltrexone, nalmefene and disulfiram are the only approved 'alcohol-specific' drugs. Acamprosate and naltrexone have been evaluated in numerous clinical trials and represent evidence-based treatments in AUDs. Nalmefene use, however, is controversial. Supervised disulfiram is a second-line treatment approach. Compounds developed and licensed for different neuropsychiatric disorders are potential alternatives. Encouraging results have been reported for topiramate, gabapentin and also varenicline, which might be useful in patients with comorbid nicotine dependence. The GABA (γ-aminobutyric acid)-B receptor agonist baclofen has shown mixed results; it is currently licensed for the treatment of AUDs in France only. Gabapentin may be close to approval in the USA. Further studies of these novel treatment approaches in AUDs are needed.
Rationale for combining acamprosate and naltrexone for treating alcohol dependence. [2019]This article provides an evidence-based review of acamprosate and naltrexone, used alone and in combination. Both medications are gaining increasing availability worldwide by prescription for the treatment of alcohol dependence. There is scientific and clinical interest in examining these drugs in combination, given their high tolerability, moderate effect sizes, different pharmacological profiles and potentially different effects on drinking outcomes.
Naltrexone versus acamprosate in the treatment of alcohol dependence: A multi-centre, randomized, double-blind, placebo-controlled trial. [2022]To compare the efficacy of acamprosate and naltrexone in the treatment of alcohol dependence.
The neurobiology, clinical efficacy and safety of acamprosate in the treatment of alcohol dependence. [2018]Acamprosate, marketed under the brand name Campral, (Forest Pharmaceuticals, Inc., Saint Louis, MO, USA; Merck Sante s.a.s., Lyon, France) is an orally administered drug approved in the US and throughout much of the world for treating alcohol dependence. Its safety and efficacy have been demonstrated in a number of clinical trials worldwide and as with all pharmacotherapies for alcoholism, it is used in conjunction with psychosocial interventions.
Naltrexone long-acting formulation in the treatment of alcohol dependence. [2021]While oral naltrexone has a demonstrated ability to decrease alcohol reinforcement, it also has pharmacotherapeutic limitations, such as a small treatment effect size, adverse events, and plasma level fluctuations. The pharmacokinetic profile of naltrexone could be enhanced by intramuscular administration, which would sustain its release over several weeks and keep plasma levels relatively constant, ie, low enough to minimize side effects but high enough to reduce drinking. Vivitrex((R))/Vivitrol((R)) and Naltrel((R)) are injectable naltrexone depot formulations that have been tested as possible medications for treating alcohol dependence. Their adverse-event profiles appear to be less severe than that of oral naltrexone. Vivitrex((R))/Vivitrol((R)) has demonstrated efficacy at decreasing heavy drinking among alcohol-dependent males. Naltrel((R)) helped to promote abstinence and decrease the incidence of relapse in two samples of alcohol-dependent subjects. The data on a third formulation, Depotrex((R)), are still limited. All three formulations require further study of their efficacy.
Efficacy and safety of naltrexone and acamprosate in the treatment of alcohol dependence: a systematic review. [2018]To ascertain the efficacy and safety of naltrexone and acamprosate in the treatment of alcohol dependence.
A pharmacokinetic and pharmacodynamic drug interaction study of acamprosate and naltrexone. [2018]Acamprosate and naltrexone have each demonstrated safety and efficacy for alcohol dependence in placebo-controlled clinical trials. There is scientific and clinical interest in evaluating these drugs in combination, given their high tolerability, moderate effect sizes, different pharmacological profiles and potentially different effects on drinking outcomes. Thus, this is the first human pharmacokinetic and pharmacodynamic drug interaction study of acamprosate and naltrexone. Twenty-four normal, healthy adult volunteers participated in a double-blind, multiple dose, within subjects, randomized, 3-way crossover drug interaction study of the standard therapeutic dose of acamprosate (2 g/d) and the standard therapeutic dose of naltrexone (50 mg/d), given alone and in combination, with seven days per treatment condition and seven days washout between treatments. Blood samples were collected on a standardized schedule for pharmacokinetic analysis of naltrexone, 6-beta-naltrexol, and acamprosate. A computerized assessment system evaluated potential drug effects on cognitive functioning. Coadministration of acamprosate with naltrexone significantly increased the rate and extent of absorption of acamprosate, as indicated by an average 33% increase in acamprosate maximum plasma concentration, 33% reduction in time to maximum plasma concentration, and 25% increase in area under the plasma concentration-time curve. Acamprosate did not affect the pharmacokinetic parameters of naltrexone or 6-beta-naltrexol. A complete absence of negative interactions on measures of safety and cognitive function supports the absence of a contraindication to co-administration of acamprosate and naltrexone in clinical practice.
Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism: a double-blind, placebo-controlled study. [2019]Naltrexone and acamprosate have been shown to be effective in relapse prevention of alcoholism via different pharmacologic mechanisms. Since it remains uncertain whether both substances are equally efficient and whether a combination of both drugs potentiates the efficacy, we conducted the first published controlled study comparing and combining both compounds.