Naltrexone for Alcoholism

(ABSTAIN Trial)

Overseen By Jazryn Nagum

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Milky Kohno

Must not be taking: Psychotropics, Opioids

Disqualifiers: Neurological, Endocrine, Hepatic, 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: 10

Duration: 12 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests naltrexone, a drug that may help reduce cravings and support abstinence in individuals with Alcohol Use Disorder (AUD). Researchers aim to understand how factors like trauma and gender affect the brain and body's response to this treatment. Participants will take either naltrexone or a placebo (a pill with no active drug) for 12 weeks. Veterans using VA healthcare who have been diagnosed with AUD might be a good fit for this study. As a Phase 4 trial, naltrexone is already FDA-approved and proven effective, and this research seeks to understand how the treatment benefits more patients.

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 use psychotropic or opioid medications, or if you are on hormonal therapy other than contraceptives.

What is the safety track record for Naltrexone?

Research has shown that naltrexone is generally safe for treating alcohol use disorder (AUD). This FDA-approved medication helps reduce cravings and supports abstinence. Studies have found it effective for many people with AUD.

Naltrexone is usually easy to tolerate. Common side effects include nausea, headache, dizziness, and tiredness, which are typically mild and often improve over time. Serious side effects are rare, but informing a healthcare provider about any liver issues before starting the medication is important.

Naltrexone has been safely used in people with alcohol dependence. It helps control cravings and reduces the number of heavy drinking days, making it a reliable choice for those wanting to cut back on alcohol. Clinical trial participants are closely monitored to ensure their safety. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Naltrexone is unique because it works by blocking opioid receptors in the brain, reducing cravings and the rewarding effects of alcohol. Unlike some treatments for alcohol use disorder (AUD) that focus solely on counseling or behavioral therapy, Naltrexone directly targets the neurological pathways associated with alcohol dependence. Researchers are excited about Naltrexone because it offers a pharmacological approach that can complement therapy, potentially leading to better outcomes for individuals struggling with AUD. By addressing the biological aspect of addiction, Naltrexone provides a more comprehensive treatment strategy.

What is the effectiveness track record for Naltrexone in treating Alcohol Use Disorder?

Studies have shown that naltrexone helps people with Alcohol Use Disorder (AUD) drink less. Research indicates that taking naltrexone can reduce the urge to drink and increase the number of sober days. In this trial, participants with AUD will receive either oral naltrexone or a placebo. One study supported using oral naltrexone as a main treatment for AUD, showing it can help reduce days of heavy drinking. Another study found that naltrexone, when combined with counseling, led to fewer days of heavy drinking in people with alcohol dependence. Overall, naltrexone is a well-supported option for treating AUD and helping people reduce their drinking. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals with Alcohol Use Disorder (AUD) who are interested in how trauma and sex differences affect their condition. Participants will undergo various assessments, provide biological samples, take a daily study drug or placebo for 12 weeks, and attend regular follow-up exams.

Inclusion Criteria

Veteran enrolled in VHA healthcare

Alcohol Group: Must meet diagnosis for recent alcohol-use disorder (DSM-V)

Control Group: Must not meet DSM-V criteria for a use disorder other than nicotine

Exclusion Criteria

Current participation in an investigational drug study

MRI contraindications (e.g. metal in body)

Positive urine drug screen, except for nicotine and marijuana, on test days

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Participants complete behavioral, neuropsychological, and neurocognitive assessments, and provide biological samples

1-2 weeks

1 visit (in-person)

Treatment

Participants take a study drug (Naltrexone or placebo) once daily for 12 weeks, with weekly assessment calls and bi-weekly medical follow-up safety exams

12 weeks

6 visits (in-person), 6 calls (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Naltrexone

Trial Overview The trial tests Naltrexone's effectiveness in reducing alcohol cravings and promoting abstinence in AUD patients. It explores the impact of trauma on emotion regulation, inflammation, brain function, and whether treatment effects differ between sexes.

How Is the Trial Designed?

Group I: Alcohol Use Disorder (AUD) Experimental Treatment 1 Intervention

Drug: Naltrexone Half of the study participants with AUD will take an oral tablet of 50 mg naltrexone once daily for one week followed by 11 weeks of 100 mg naltrexone orally, once daily. Drug: Placebo oral tablet The other half of study participants will receive an identical looking placebo in tablet form and take the medication using an identical schedule as the real drug. Drug type will be randomized.

Group II: Healthy Controls Active Control 1 Intervention

Baseline measures will be taken but controls will not continue to the drug trial.

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?

Milky Kohno

Lead Sponsor

Trials

1

Recruited

100+

Portland VA Medical Center

Collaborator

Trials

44

Recruited

7,800+

Published Research Related to This Trial

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 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]

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 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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6881114/

Treatment outcomes of long-acting injectable naltrexone ... In veterans, the prevalence of 12-month and lifetime alcohol use disorder (AUD) is 14.8% and 42.2%, respectively. Alcohol use disorder ...

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

Pharmacotherapy for Alcohol Use Disorder: A Systematic ... These findings support the use of oral naltrexone at 50 mg/d and acamprosate as first-line pharmacotherapies for alcohol use disorder.

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

Alcohol Dependence: VIVITROL ® Efficacy and Safety Data VIVITROL and counseling may help your appropriate patients with alcohol dependence achieve fewer heavy drinking days.

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

Naltrexone and Alcohol Use | American Journal of Psychiatry Prescribing naltrexone for alcohol misuse continues to be one of the most underutilized interventions in medicine. Alcohol use disorder (AUD) ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2376083/

Naltrexone long-acting formulation in the treatment of alcohol ... Vivitrex ® /Vivitrol ® and Naltrel ® are injectable naltrexone depot formulations that have been tested as possible medications for treating alcohol dependence.

6. 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.

7. 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 ...

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK534811/

Naltrexone - StatPearls - NCBI Bookshelf Naltrexone is an FDA-approved opioid antagonist used to treat alcohol use disorder and opioid dependence. Naltrexone blocks the effect of ...

9. 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 ...