Lemborexant + Naltrexone for Alcoholism

Overseen By Nadine Obeid, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Baylor College of Medicine

Must not be taking: Opioids, Benzodiazepines, Hypnotics

Disqualifiers: Unstable medical conditions, Drug use disorder, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

8 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a combination of naltrexone, which reduces alcohol cravings, and lemborexant, a sleep aid, in people with alcohol use disorder and insomnia. The goal is to see if this combination can better manage both alcohol cravings and sleep problems compared to using naltrexone alone. Improving sleep may help reduce the risk of relapse in these patients. Naltrexone has been widely studied and shown to reduce alcohol cravings and intake in alcohol-dependent individuals.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot use naltrexone, lemborexant, opioid medications, scheduled benzodiazepines, or hypnotics before joining. Other stable medications might be allowed.

What data supports the effectiveness of the drug Lemborexant + Naltrexone for treating alcoholism?

Research shows that naltrexone, one of the drugs in the treatment, has been effective in reducing heavy drinking and improving outcomes when combined with psychosocial support. The extended-release form of naltrexone, Vivitrol, has been particularly noted for its effectiveness in treating alcohol dependence. ^{1 2 3 4 5}

Is the combination of Lemborexant and Naltrexone safe for humans?

Naltrexone, especially in its extended-release form (Vivitrol), is generally considered safe for treating alcohol dependence, with a more stable level in the body that may lead to fewer side effects. However, it can have liver-related side effects, particularly in people with liver conditions like hepatitis C. There is no specific safety data available for Lemborexant in combination with Naltrexone. ^{2 3 6 7 8}

How is the drug Lemborexant + Naltrexone unique for treating alcoholism?

The combination of Lemborexant and Naltrexone for treating alcoholism is unique because it potentially combines the effects of Naltrexone, which reduces alcohol cravings, with Lemborexant, a medication that may help with sleep issues often associated with alcohol withdrawal. This combination could address both the physical and psychological aspects of alcohol dependence, offering a novel approach compared to using Naltrexone alone. ^{3 7 9 10 11}

Eligibility Criteria

This trial is for adults aged 18-65 with alcohol use disorder and insomnia, as diagnosed by DSM-5 criteria. Participants must not have used opioids or certain sedatives recently, be free from acute alcohol withdrawal, and cannot have liver issues or other drug disorders (except nicotine/cannabis). Pregnant/breastfeeding individuals or those with a known sensitivity to the study drugs are excluded.

Inclusion Criteria

diagnosis of alcohol use disorder using the DSM-5 criteria confirmed with SCID-5 and

You have a history of alcohol use disorder and meet the criteria for alcohol use disorder as specified in the DSM-5.

I am between 18 and 65 years old.

Exclusion Criteria

My liver function tests are not more than 3 times the normal limit.

You have a substance use disorder, except for nicotine and cannabis.

I have been diagnosed with narcolepsy and may have other stable health conditions or use psychiatric medications.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either Lemborexant plus Naltrexone or Placebo plus Naltrexone for alcohol craving and sleep issues

4 weeks

Weekly visits (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Lemborexant
• Naltrexone

Trial Overview The study aims to see if adding Lemborexant to Naltrexone helps reduce alcohol cravings more than just Naltrexone alone in people with both alcoholism and sleep problems. It also looks at how this combination affects sleep quality, mood, and thoughts of self-harm.

Participant Groups

Group I: Lemborexant plus Naltrexone Active Control 2 Interventions

10 milligrams of Lemborexant will be given daily at nighttime and 50 milligrams of Naltrexone will be given daily for a total of 4 weeks

Group II: Placebo plus Naltrexone Placebo Group 1 Intervention

10 milligrams of placebo will be given daily at nighttime and 50 milligrams of Naltrexone will be given daily for a total of 4 weeks

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

Approved in United States as Vivitrol for:

• Alcohol dependence
• Opioid use disorder

Approved in European Union as Naltrexone for:

• Opioid dependence
• Alcohol dependence

Approved in Canada as Vivitrol for:

• Opioid use disorder
• Alcohol dependence

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Findings from Research

A systematic review of 29 randomized placebo-controlled trials involving 5997 alcohol-dependent patients found that naltrexone significantly reduces heavy drinking in 70% of the studies, highlighting its efficacy in this area.

However, naltrexone showed less effectiveness in promoting abstinence, with only 36% of trials demonstrating an advantage over placebo, suggesting that its primary benefit lies in reducing excessive drinking rather than achieving complete sobriety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The status of naltrexone in the treatment of alcohol dependence: specific effects on heavy drinking. Pettinati, HM., O'Brien, CP., Rabinowitz, AR., et al.[2013]

The FDA-approved extended-release injectable formulation of naltrexone (Vivitrol) offers a promising alternative to daily oral medication for alcohol dependence, potentially improving adherence and treatment outcomes.

When combined with psychosocial support, long-acting naltrexone has shown significant improvements in drinking outcomes, particularly for patients who are abstinent at the start of treatment, suggesting its efficacy in managing alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting injectable naltrexone for the treatment of alcohol dependence. Mannelli, P., Peindl, K., Masand, PS., et al.[2013]

A systematic review of 49 trials found that only 14% of studies on naltrexone for alcohol dependence had high adherence assurance, which may explain the variability in treatment efficacy observed.

The study revealed a significant correlation between adherence levels and treatment outcomes, suggesting that improving adherence monitoring could enhance the effectiveness of naltrexone in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence monitoring in naltrexone pharmacotherapy trials: a systematic review. Swift, R., Oslin, DW., Alexander, M., et al.[2022]

In a study of 149 alcohol-dependent patients, those receiving broad-spectrum treatment (BST) combined with naltrexone had significantly more days of abstinence compared to those receiving motivational-enhancement therapy (MET) with naltrexone.

The effectiveness of BST was particularly pronounced in patients with supportive social networks, indicating that BST may provide a meaningful clinical advantage over MET when used alongside naltrexone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Building better cognitive-behavioral therapy: is broad-spectrum treatment more effective than motivational-enhancement therapy for alcohol-dependent patients treated with naltrexone? Davidson, D., Gulliver, SB., Longabaugh, R., et al.[2019]

In a 12-week clinical trial with 202 alcohol-dependent patients, naltrexone significantly reduced the relapse rate to heavy drinking (7.9% for naltrexone vs. 18.8% for placebo), indicating its efficacy in treating alcoholism.

Naltrexone was well-tolerated with low rates of adverse events, such as abdominal pain and headache, and it did not negatively affect liver function or biochemical markers of heavy drinking, demonstrating its safety in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, placebo-controlled study of naltrexone in the treatment of alcohol-dependence disorder: results from a multicenter clinical trial. Guardia, J., Caso, C., Arias, F., et al.[2013]

A study involving 250 opioid-dependent patients, many of whom had chronic hepatitis C virus (HCV) and HIV, found that intramuscular extended-release naltrexone (XR-NTX) did not significantly increase liver enzyme levels compared to a placebo, indicating its safety in this population.

Even though some patients experienced elevated liver enzymes, these levels improved over time, and no specific symptoms were linked to these elevations, suggesting that XR-NTX can be safely administered to patients with mild to moderate chronic HCV and/or HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic safety of injectable extended-release naltrexone in patients with chronic hepatitis C and HIV infection. Mitchell, MC., Memisoglu, A., Silverman, BL.[2019]

A population pharmacokinetic analysis of 453 subjects showed that the clearance and distribution of naltrexone, used for alcohol dependence, are influenced by factors like weight and age, but these differences are not clinically significant enough to require dosage adjustments.

The study found that naltrexone clearance was higher in individuals with alcohol and/or opioid dependence compared to healthy subjects, indicating that while there are variations in pharmacokinetics, standard dosing of XR-NTX remains appropriate across different subpopulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics of extended-release injectable naltrexone (XR-NTX) in patients with alcohol dependence. Dunbar, JL., Turncliff, RZ., Hayes, SC., et al.[2019]

In a 1-year open-label extension study involving 114 patients, injectable extended-release naltrexone (XR-NTX) demonstrated long-term efficacy, with 50.9% of participants remaining abstinent from opioids throughout the study.

The treatment was generally safe, with only 21.1% of patients reporting adverse events and no severe adverse events noted, although 16.7% experienced elevated liver function tests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Injectable extended-release naltrexone for opioid dependence: an open label study of long-term safety and efficacy]. Krupitsky, EM., Nunes, EV., Ling, W., et al.[2016]

A pilot study involving 30 alcohol-dependent patients showed that the long-acting injectable naltrexone (Vivitrex) is generally safe and well tolerated, with mild to moderate adverse events that resolved without intervention.

The study confirmed that therapeutic levels of naltrexone were maintained throughout the 4-month treatment period, suggesting that this formulation could improve patient adherence by eliminating the need for daily dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot evaluation of the safety and tolerability of repeat dose administration of long-acting injectable naltrexone (Vivitrex) in patients with alcohol dependence. Johnson, BA., Ait-Daoud, N., Aubin, HJ., et al.[2019]

Extended-release naltrexone (XR-NTX) is being studied as a potentially more effective treatment for alcohol dependence compared to daily oral naltrexone (O-NTX), particularly due to its once-a-month injection format which may improve adherence and retention in treatment.

The study involves 237 participants over 24 weeks and aims to evaluate the effectiveness of XR-NTX in achieving abstinence or moderate drinking, while also assessing its cost-effectiveness compared to O-NTX in a primary care setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended-release vs. oral naltrexone for alcohol dependence treatment in primary care (XON). Malone, M., McDonald, R., Vittitow, A., et al.[2020]

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]

References

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

The status of naltrexone in the treatment of alcohol dependence: specific effects on heavy drinking. [2013]

2. England pubmed.ncbi.nlm.nih.gov

Long-acting injectable naltrexone for the treatment of alcohol dependence. [2013]

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

Adherence monitoring in naltrexone pharmacotherapy trials: a systematic review. [2022]

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

Building better cognitive-behavioral therapy: is broad-spectrum treatment more effective than motivational-enhancement therapy for alcohol-dependent patients treated with naltrexone? [2019]

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

A double-blind, placebo-controlled study of naltrexone in the treatment of alcohol-dependence disorder: results from a multicenter clinical trial. [2013]

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

Hepatic safety of injectable extended-release naltrexone in patients with chronic hepatitis C and HIV infection. [2019]

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

Population pharmacokinetics of extended-release injectable naltrexone (XR-NTX) in patients with alcohol dependence. [2019]

8. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Injectable extended-release naltrexone for opioid dependence: an open label study of long-term safety and efficacy]. [2016]

9. England pubmed.ncbi.nlm.nih.gov

A pilot evaluation of the safety and tolerability of repeat dose administration of long-acting injectable naltrexone (Vivitrex) in patients with alcohol dependence. [2019]

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

Extended-release vs. oral naltrexone for alcohol dependence treatment in primary care (XON). [2020]

11. New Zealand pubmed.ncbi.nlm.nih.gov

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