Naltrexone Injection for Alcoholism

Overseen By Rachel Weyl, BS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Pennsylvania

Must not be taking: Psychotropics, Anticonvulsants, Opioids, Anticoagulants

Disqualifiers: Planned surgery, Physical disease, Psychotic disorder, Drug use disorder, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 8 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a long-acting naltrexone injection to determine if it helps individuals who drink heavily because they find it rewarding to reduce their alcohol consumption. Participants will receive either the naltrexone injection (XR-NTX 380 mg, intramuscular) or a placebo, along with guidance on managing their drinking. It suits individuals who consume over 24 drinks per week (for men) or 18 drinks per week (for women) and wish to reduce or stop drinking. As a Phase 4 trial, this research involves an FDA-approved treatment and aims to understand how it benefits more patients.

Will I have to stop taking my current medications?

Yes, if you are currently taking psychotropic, anticonvulsant, opioid, anticoagulant, or alcohol use disorder treatment medications, you will need to stop them to participate in this trial.

What is the safety track record for these treatments?

Research has shown that XR-NTX, the injectable form of naltrexone, is usually well-tolerated by people with alcohol use disorder. Studies have found no serious liver issues in patients, even those with advanced liver disease. This is important because the liver processes many medications, and some can harm it.

The FDA has already approved naltrexone for treating alcohol and opioid use disorders, indicating its safety. In studies, people using XR-NTX experienced fewer days of heavy drinking compared to those who received a placebo, demonstrating its effectiveness and safety.

Overall, evidence suggests that XR-NTX is safe for most people, with side effects being rare and generally mild. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike most treatments for alcoholism, which are typically oral medications like disulfiram, acamprosate, or oral naltrexone, XR-NTX 380 mg is administered as an intramuscular injection. This extended-release formulation provides a steady delivery of medication over a month, reducing the need for daily dosing and improving adherence. Researchers are excited because this method could lead to more consistent therapeutic effects and better patient outcomes, as it minimizes the risk of missed doses. Additionally, the injectable form bypasses the digestive system, which can enhance the drug's effectiveness and reduce potential side effects associated with oral intake.

What evidence suggests that XR-NTX could be an effective treatment for alcoholism?

Research has shown that monthly injections of extended-release naltrexone (XR-NTX), which participants in this trial may receive, can help people with alcohol use disorder reduce their drinking. One study found that patients receiving XR-NTX with counseling experienced fewer heavy drinking days compared to those receiving a placebo. This treatment blocks the rewarding effects of alcohol. The FDA has already approved it for treating alcohol dependence, and it has proven more effective than daily naltrexone pills. Overall, XR-NTX offers a promising option for those seeking to reduce their drinking. ^{2 4 6 7 8}

Who Is on the Research Team?

Henry Kranzler, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

Adults aged 18-65 with Alcohol Use Disorder (AUD) who drink heavily and want to cut down or stop. They must be able to understand the study, have a stable address, and use reliable birth control if applicable. Excluded are those with certain mental health conditions, on conflicting medications, facing potential incarceration soon, having significant physical diseases or abnormal lab results, drug disorders other than alcohol/nicotine/cannabis, needing detoxification from alcohol or with a history of bad reactions to XR-NTX.

Inclusion Criteria

Current DSM-5 diagnosis of AUD

Primarily a reward drinker [i.e., with a score of >22 on the reward subscale and a score of <14 on the relief subscale of the Inventory of Drinking Situations (IDS)]

I am using reliable birth control and not pregnant if I can have children.

Exclusion Criteria

I don't have any major health issues that could make joining the study unsafe for me.

Current psychotic disorder (bipolar, schizophrenia, major depression with suicidal ideation, or psychotic features) identified by clinical examination or the structured interview that could interfere with study participation or make it hazardous for the subject

History of allergy or other serious adverse event due to treatment with XR-NTX

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person or virtual)

Treatment

Participants receive monthly injections of XR-NTX or placebo and complete daily IVR calls

8 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Medical Management
• Placebo intramuscular injection
• XR-NTX 380 mg, intramuscular injection

Trial Overview

The trial is testing whether long-acting injectable naltrexone (XR-NTX) helps people who primarily drink for pleasure more than a placebo in reducing heavy drinking. Participants will receive either XR-NTX or placebo injections monthly along with four sessions of Medical Management counseling over eight weeks.

How Is the Trial Designed?

Group I: XR-NTX 380 mg, intramuscular injection Active Control 2 Interventions

Subjects will receive an injection of XR-NTX 380 mg (4 mL) repeated once after 4 weeks.

Group II: Inactive placebo intramuscular injection Placebo Group 2 Interventions

Subjects will receive a placebo injection repeated once after 4 weeks.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Alkermes, Inc.

Industry Sponsor

Trials

118

Recruited

27,200+

Richard Pops

Alkermes, Inc.

Chief Executive Officer since 1991

BA in Economics from Stanford University

Dr. Craig Hopkinson

Alkermes, Inc.

Chief Medical Officer since 2017

MD

Published Research Related to This Trial

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 24-week study involving 624 alcohol-dependent patients, the 380 mg dose of extended-release naltrexone (XR-NTX) significantly improved quality of life in areas such as mental health, social functioning, and physical functioning compared to placebo.

Improvements in quality of life were correlated with reductions in drinking behaviors, indicating that XR-NTX not only helps reduce alcohol consumption but also enhances overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of extended-release naltrexone (XR-NTX) on quality of life in alcohol-dependent patients. Pettinati, HM., Gastfriend, DR., Dong, Q., et al.[2021]

In a study of 624 alcohol-dependent adults over 24 weeks, those receiving the higher dose of extended-release naltrexone (XR-NTX 380 mg) showed a slightly higher participation rate in counseling and support groups compared to placebo, suggesting that XR-NTX may encourage engagement in treatment.

Participation in self-help support groups was significantly associated with reduced heavy drinking across all treatment groups, indicating that combining XR-NTX with counseling and support can be beneficial for individuals in recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of treatment with intramuscular, injectable, extended-release naltrexone on counseling and support group participation in patients with alcohol dependence. Cisler, RA., Silverman, BL., Gromov, I., et al.[2011]

In a 24-week study involving 250 recently detoxified opioid-dependent adults, those treated with once-monthly extended-release naltrexone (XR-NTX) had a significantly higher rate of achieving 90% abstinence from opioids compared to those receiving a placebo (51% vs 31%).

The study found that XR-NTX was effective across various demographic and clinical severity characteristics, indicating that it can be a suitable treatment option for a broad range of patients without needing specific matching factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating Opioid Dependence With Injectable Extended-Release Naltrexone (XR-NTX): Who Will Respond? Nunes, EV., Krupitsky, E., Ling, W., et al.[2022]

In a study of 82 patients who had abstained from alcohol for at least 4 days, extended-release naltrexone (XR-NTX) 380 mg significantly increased the rate of abstinence compared to placebo, with a median time to first drink of 41 days versus 12 days.

XR-NTX 380 mg also led to a substantial reduction in heavy drinking days (93% decrease) and overall drinking days (90% decrease), indicating its efficacy in promoting sustained abstinence and reducing alcohol consumption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of extended-release naltrexone in alcohol-dependent patients who are abstinent before treatment. O'Malley, SS., Garbutt, JC., Gastfriend, DR., et al.[2013]

Extended release naltrexone (XR-NTX) significantly reduces relapse rates in individuals with opioid use disorder, showing effectiveness across diverse demographic and psychological backgrounds, based on a study involving 308 participants.

However, individuals who reported alcohol intoxication in the 30 days prior to treatment had similar relapse rates to those receiving standard treatment, suggesting that recent alcohol use may limit the effectiveness of XR-NTX.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do patient characteristics moderate the effect of extended-release naltrexone (XR-NTX) for opioid use disorder? Friedmann, PD., Wilson, D., Nunes, EV., et al.[2019]

Citations

1.

pmc.ncbi.nlm.nih.gov

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

Naltrexone long-acting formulation in the treatment of alcohol ...

Clinical evidence suggests that Vivitrex®/Vivitrol® can diminish heavy drinking among men but not women. The reason for this difference in efficacy is still ...

2.

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 ...

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1551714418305627

Extended-release vs. oral naltrexone for alcohol ...

Extended-release naltrexone (XR-NTX, Vivitrol®) and daily oral naltrexone tablets (O-NTX) are FDA-approved mu opioid receptor antagonist medications for ...

4.

recoveryanswers.org

recoveryanswers.org/research-post/underused-tool-alcohol-use-evaluating-effectiveness-extended-release-injectable-naltrexone/

An underused tool for alcohol use disorder: Evaluating the ...

Naltrexone is also available in an extended-release injectable formulation (XR naltrexone, also known as the brand name “Vivitrol”). Since XR naltrexone is ...

5.

pmc.ncbi.nlm.nih.gov

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

Treatment outcomes of long-acting injectable naltrexone ...

... naltrexone, alcohol use disorder, AUD, substance use disorder, SUD, veterans ... Vivitrol (naltrexone) injection. DailyMed. 1984 [rev. December ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40515940/

Safety and Tolerability of Injectable Extended-Release ...

In this case series, XR-NTX was well tolerated in patients with advanced ALD, without evidence of hepatotoxicity or liver decompensation.

7.

jamanetwork.com

jamanetwork.com/journals/jamanetworkopen/fullarticle/2818410

Rapid Initiation of Injection Naltrexone for Opioid Use ...

The results of this trial suggest that rapid initiation could make XR-naltrexone a more viable treatment for patients with OUD.

8.

samhsa.gov

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

What is Naltrexone? Side Effects, Uses, Dose & Risk

Naltrexone is a medication approved by the Food and Drug Administration (FDA) to treat both opioid use disorder (OUD) and alcohol use disorder (AUD).