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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assist individuals with alcohol use disorder (AUD) who visit the emergency department. It begins by offering oral naltrexone, a medication known to reduce alcohol cravings, to interested patients in the emergency room. Patients will then connect to outpatient care for ongoing treatment with monthly Vivitrol injections, a form of naltrexone. This trial suits individuals visiting the emergency department due to alcohol issues and who wish to reduce their drinking. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, providing an opportunity to benefit from established care.

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 is the safety track record for Naltrexone?

Research has shown that naltrexone is generally safe for people with alcohol use disorder. The FDA has approved this medication, indicating it has passed strict safety tests. Studies have found that naltrexone can help reduce heavy drinking days when combined with counseling.

Some individuals might experience side effects like nausea or headaches, but serious issues are rare. It is also safe for people with liver disease, though monitoring may be necessary. Overall, naltrexone's safety offers reassurance for those considering it as a treatment. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Naltrexone is unique because it targets alcohol dependence by blocking the pleasurable effects of alcohol in the brain, which can reduce the craving and urge to drink. Unlike some other treatments that focus on abstinence, naltrexone can help people manage their drinking by making the experience less rewarding. Researchers are particularly excited about the injectable form of naltrexone offered in this trial, which provides a monthly dose, increasing adherence and convenience compared to daily oral medications. This approach helps ensure that individuals receive consistent treatment, potentially improving their outcomes in battling alcohol dependence.

What is the effectiveness track record for naltrexone in treating alcohol use disorder?

Research has shown that naltrexone can assist individuals with alcohol use disorder (AUD). One study found that those taking naltrexone achieved 15% better results than those who did not. Naltrexone also reduces the risk of returning to heavy drinking. In this trial, participants will initially receive oral naltrexone, followed by monthly injections of Vivitrol, an injectable form of naltrexone. Studies indicate that individuals who received Vivitrol along with counseling experienced fewer days of heavy drinking compared to those who only received counseling. Overall, naltrexone aids in managing AUD by reducing drinking and preventing relapse. ^{1 5 6 7}

Who Is on the Research Team?

David Hui, MD

Principal Investigator

Albert Einstein Medical Center

Are You a Good Fit for This Trial?

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 want to cut down or stop drinking alcohol.

AUDIT score greater or equal to 16

Presents to the ED with chief complaint of alcohol use or judged to have alcohol use as a significant contributing factor to their presentation to the emergency department

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2565602/

Naltrexone for the Management of Alcohol Dependence - PMC In the group that received naltrexone, there was an absolute increase of approximately 15% in good clinical outcomes (73.7%, as compared with 58.2% in the ...

2. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2811435

Pharmacotherapy for Alcohol Use Disorder: A Systematic ... Compared with placebo, oral naltrexone (50 mg/d) was associated with lower rates of return to heavy drinking, with a number needed to treat of ...

3. vivitrolhcp.com vivitrolhcp.com/alcohol-dependence-pivotal-study

Alcohol Dependence: VIVITROL ® Efficacy and Safety Data Patients in the VIVITROL and counseling group had a greater reduction in days of heavy drinking than those in the placebo and counseling group. 1,2. 25%. Fewer ...

4. psychiatryonline.org psychiatryonline.org/doi/full/10.1176/appi.ajp.20220821

Naltrexone and Alcohol Use | American Journal of Psychiatry They have been shown to improve numerous drinking outcomes, including a return to any drinking and a return to heavy drinking (5). As an opioid ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9701476/

Naltrexone for alcohol use disorder: Hepatic safety in ... Naltrexone is an approved drug for management of alcohol use disorder (AUD), but data in patients with liver disease (LD) are limited.

6. samhsa.gov samhsa.gov/substance-use/treatment/options/naltrexone

What is Naltrexone? Side Effects, Uses, Dose & Risk Intramuscular extended release naltrexone is a medication approved by the Food and Drug Administration (FDA) to treat both opioid use ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2013/018932s017lbl.pdf

REVIA (naltrexone hydrochloride tablets USP) 50 mg Opioid ... REVIA is a pure opioid antagonist. It markedly attenuates or completely blocks, reversibly, the subjective effects of intravenously administered opioids. When ...