Naltrexone for Alcoholism

Overseen By Serge Simpson, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Albert Einstein Healthcare Network

Must be taking: Naltrexone

Must not be taking: Opioids

Disqualifiers: Opioid dependence, Liver disease, Pregnant, others

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

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: 4

20 Participants Needed

Trial Summary

What is the purpose of this trial?

Alcohol use disorder (AUD) is a treatable and common condition encountered in the emergency department, but unfortunately is rarely directly addressed in emergency departments nationwide. To our knowledge, initiation of medication assisted therapy (MAT) for AUD in the emergency department setting has not been widely adopted. Our project is novel for its scope to use a medication well-tested in the outpatient environment and bring it to the emergency department in order to more effectively link patients to outpatient alcohol use reduction therapy as part of a medication assisted therapy (MAT). The investigators are proposing a feasibility project to initiate oral naltrexone to eligible ED patients deemed to have alcohol use disorder and who are interested in cutting down their drinking. The investigators plan to connect these patients with outpatient follow-up in our own community practice center (CPC) for intramuscular (IM) Vivitrol injections under the supervision of the Einstein Toxicology Department. Through the CPC, patients can also be referred to other supporting services such as Alcoholics Anonymous for multidisciplinary care. The investigators are optimistic that this innovative warm hand off from the initial ED visit to outpatient follow-up will ultimately decrease problematic drinking, improve patient's health, and benefit the hospital. Our main objective is to establish a pathway to encourage patients who present to the emergency room with acute sequelae of alcohol use disorder to enter outpatient treatment. Our intervention will be the initiation of oral naltrexone with warm handoff to the Community Practice Center where patients will be transitioned to intramuscular (IM) Vivitrol for chronic maintenance therapy. Thus success will be measured by primarily: percentage of patients who make it to their first outpatient visit for the Vivitrol injection, percentage of patients who continue with treatment and continue to receive Vivitrol for their second injection.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are dependent on opioid medications or street drugs, you cannot participate in the trial.

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

Research shows that Naltrexone can help reduce alcohol cravings and drinking, and lower relapse rates in people with alcohol dependence. It is more effective when combined with counseling and support, and a long-acting injectable form may improve adherence and outcomes. ^{1 2 3 4 5}

Is naltrexone safe for humans?

Naltrexone, used for alcohol and opioid dependence, is generally safe but can have side effects. Injectable forms like Vivitrol have fewer side effects than oral versions, but there is a potential risk of liver issues and overdose after stopping treatment. ^{1 3 6 7 8}

What makes the drug Naltrexone unique for treating alcoholism?

Naltrexone is unique for treating alcoholism because it works by blocking opioid receptors in the brain, which reduces the pleasurable effects of alcohol and helps decrease cravings. Unlike some other treatments, it can be administered as a monthly injection (Vivitrol) or taken as a daily pill (ReVia, Depade), offering flexibility in how it is used. ^{9 10 11 12 13}

Research Team

David Hui, MD

Principal Investigator

Albert Einstein Medical Center

Eligibility Criteria

This trial is for adults over 18 who show up at the emergency department with alcohol-related issues, want to cut down or stop drinking, and have an AUDIT score of 16 or higher. It's not for those with severe liver disease, allergies to naltrexone, pregnant women, prisoners, non-English speakers without contact means, opioid users, or anyone unable to consent.

Inclusion Criteria

I am 18 years old or older.

I want to cut down or stop drinking alcohol.

AUDIT score greater or equal to 16

Exclusion Criteria

Elevated liver transaminase (AST or ALT) that is greater than 5 times the upper limit of normal

I will be admitted to the hospital.

My liver is not working properly.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment Initiation

Participants receive their first dose of oral naltrexone in the ED and are discharged with a week's prescription for daily oral naltrexone

1 week

1 visit (in-person)

Outpatient Transition

Participants are transitioned to outpatient MAT clinic for intramuscular Vivitrol injections and multidisciplinary care

4 weeks

1 visit (in-person) for initial injection, monthly follow-up visits

Follow-up

Participants are monitored for treatment adherence and effectiveness, including assessment of alcohol use severity and cravings

4 weeks

1 follow-up visit (in-person)

Treatment Details

Interventions

• Naltrexone

Trial Overview The study tests if starting oral naltrexone in the emergency department can help link patients with alcohol use disorder to outpatient therapy. Success will be measured by how many follow-up for Vivitrol injections at a community center and continue treatment.

Participant Groups

Group I: Participant Experimental Treatment 1 Intervention

All participants who meet inclusion criteria will be offered oral naltrexone in the ED, a bridge prescription for oral naltrexone, and be referred to outpatient MAT clinic where participants will be offered monthly IM naltrexone injections.

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?

Albert Einstein Healthcare Network

Lead Sponsor

Trials

65

Recruited

869,000+

Findings from Research

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]

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]

In a study involving 99 men, naltrexone treatment significantly reduced alcohol cravings and drinking, and led to lower relapse rates compared to placebo, indicating its efficacy in treating alcohol dependence.

Naltrexone is considered a safe and effective adjunct to psychosocial interventions for alcohol dependence, with better outcomes observed in patients who consistently attended all treatment visits, suggesting that adherence to the treatment program enhances its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone in the treatment of alcoholism: a clinical review. O'Brien, CP., Volpicelli, LA., Volpicelli, JR.[2019]

In a study of 603 participants from the COMBINE Study, family history of alcoholism (FHA) was linked to increased alcohol consumption per drinking occasion, indicating that individuals with a stronger FHA may drink more when they do drink.

While naltrexone showed a significant effect on reducing heavy drinking days over time, the study found that FHA did not significantly influence the effectiveness of naltrexone, suggesting that other factors may be more important in determining treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does family history of alcoholism moderate naltrexone's effects on alcohol use? Capone, C., Kahler, CW., Swift, RM., et al.[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]

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 review of 263 cases related to Vivitrol (extended-release naltrexone) found that 84.6% of fatal overdoses occurred within two months after the last injection, highlighting a critical period for overdose risk.

The study suggests that there may be a link between Vivitrol discontinuation and increased overdose risk, indicating the need for further investigation and monitoring during this time frame.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of Case Narratives from Fatal Overdoses Associated with Injectable Naltrexone for Opioid Dependence. Saucier, R., Wolfe, D., Dasgupta, N.[2019]

Falecalcitriol, a vitamin D analogue designed to avoid metabolism by CYP24A1, has been used since 2001 to treat secondary hyperparathyroidism, demonstrating its efficacy in managing this condition.

The 23-hydroxy metabolite of falecalcitriol retains biological activity and is resistant to further metabolism, which may enhance its therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent developments for introducing a hexafluoroisopropanol unit into the Vitamin D side chain. Kawagoe, F., Sugiyama, T., Uesugi, M., et al.[2019]

In a 12-week study involving 30 patients with stable plaque psoriasis, both calcipotriol and calcitriol combined with NBUVB phototherapy significantly reduced symptoms like erythema and scaling, showing effectiveness as treatments.

Calcipotriol was found to be more effective than calcitriol, leading to quicker plaque clearance and a lower relapse rate, while also requiring fewer NBUVB treatment sessions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative evaluation of efficacy and safety of calcipotriol versus calcitriol ointment, both in combination with narrow-band ultraviolet B phototherapy in the treatment of stable plaque psoriasis. Chakraborty, D., Aggarwal, K.[2023]

The study identified a novel VDR agonist, 22S-butyl-20-epi-25,26,27-trinorvitamin D derivative 5, which induces a unique structure in the vitamin D receptor's ligand-binding pocket, enhancing its potency.

In contrast, the compound 4 with the natural configuration at C(20) acts as a potent VDR antagonist, creating a new cavity in the receptor structure, marking the first instance of a VDR antagonist altering the canonical pocket architecture.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new class of vitamin D analogues that induce structural rearrangement of the ligand-binding pocket of the receptor. Inaba, Y., Yoshimoto, N., Sakamaki, Y., et al.[2019]

Gemini analogs of calcitriol, like BXL0124, are more effective agonists of the vitamin D receptor (VDR) than calcitriol, showing enhanced biological activity due to a structural rearrangement that allows for better binding.

BXL0124 demonstrated superior anti-cancer properties, specifically in inhibiting breast cancer cell growth and reducing tumor volume compared to its counterpart BXL0097, indicating its potential as a more potent therapeutic agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Structural analysis and biological activities of BXL0124, a gemini analog of vitamin D. Belorusova, AY., Suh, N., Lee, HJ., et al.[2018]

The active form of vitamin D(3), calcitriol, has been shown to inhibit the growth and spread of prostate and liver cancer cells, suggesting its potential use in cancer therapy.

Newly developed vitamin D analogs, such as MART-10 and MART-11, show promise as effective cancer treatments with reduced risk of hypercalcemia, making them safer alternatives for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potent 19-norvitamin D analogs for prostate and liver cancer therapy. Kittaka, A., Yoshida, A., Chiang, KC., et al.[2021]

References

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

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

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

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

3. England pubmed.ncbi.nlm.nih.gov

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

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

Naltrexone in the treatment of alcoholism: a clinical review. [2019]

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

Does family history of alcoholism moderate naltrexone's effects on alcohol use? [2019]

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

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

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

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

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

Review of Case Narratives from Fatal Overdoses Associated with Injectable Naltrexone for Opioid Dependence. [2019]

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

Recent developments for introducing a hexafluoroisopropanol unit into the Vitamin D side chain. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Comparative evaluation of efficacy and safety of calcipotriol versus calcitriol ointment, both in combination with narrow-band ultraviolet B phototherapy in the treatment of stable plaque psoriasis. [2023]

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

A new class of vitamin D analogues that induce structural rearrangement of the ligand-binding pocket of the receptor. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Structural analysis and biological activities of BXL0124, a gemini analog of vitamin D. [2018]

13. England pubmed.ncbi.nlm.nih.gov

Potent 19-norvitamin D analogs for prostate and liver cancer therapy. [2021]