Alirocumab for Alcohol Use Disorder

Overseen By Nada M Saleh

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Must not be taking: Statins, PCSK9 inhibitors, Corticosteroids, others

Disqualifiers: Cardiovascular disease, Diabetes, Cancer, others

Compensation: Varies

Number of Visits: 9

Duration: 8 weeks

100 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: Drinking alcohol can lead to swelling and injury in the liver. Long-term heavy drinking may lead to liver disease. Researchers want to study the relationship between a drug called alirocumab, alcohol use, and liver functioning/swelling. Objective: To study the effects of alirocumab in people who drink alcohol. Eligibility: Healthy adults ages 21 to 65 who regularly consume an average of 20 or more drinks per week. Design: Participants will be screened under protocol 14-AA-0181. Participants will get alirocumab or a placebo as an injection under the skin. Participants will give blood and urine samples. They will have physical exams. Participants will have FibroScans . It measures liver and spleen stiffness. Participants will lie on a table. They will expose the lower right and left side of their chest. The machine will send a small vibration to the liver. Participants may have magnetic resonance imaging (MRI) scans of the liver. The MRI scanner is shaped like a cylinder. Participants will lie on a table that slides in and out of the scanner. A device called a coil will be placed over their liver. Participants will have a Doppler scan and ultrasound. These tests measure blood flow in the body. Participants will have an electrocardiogram. It measures heart function. Participants will fill out surveys about how they are feeling, their alcohol consumption, and other behaviors. They will complete cognitive tasks on a computer. Participants will meet with a clinician. They will discuss the participant s assessment results, patterns of drinking, and possibly stopping or cutting down on drinking. Participation will last for 8 weeks. Participants will have 9 study visits.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking certain medications, such as statins and fibrates, before participating. If you are on these medications, you must stop using them at least eight weeks (for statins) or six weeks (for fibrates) before the study begins. Other medications that interfere with blood clotting or require intramuscular injections are also not allowed.

How does the drug Alirocumab differ from other drugs for alcohol use disorder?

Alirocumab is unique because it is primarily used to lower cholesterol levels by targeting a protein called PCSK9, which is different from the usual drugs for alcohol use disorder that focus on neurotransmitter systems. This novel approach could offer a new pathway for treating alcohol use disorder, although its effectiveness for this condition is still being studied. ^{1 2 3 4 5}

Research Team

Falk W Lohoff, M.D.

Principal Investigator

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Eligibility Criteria

Adults aged 21-65 who are heavy drinkers (consuming over 20 drinks weekly) but not seeking treatment for alcohol use can join. They must be generally healthy, with liver tests showing some elevation. Women must test negative for pregnancy and agree to contraception; men also need to commit to using contraception.

Inclusion Criteria

Alanine aminotransferase and/or aspartate aminotransferase and/or gamma-glutamyl transferase exceeding the upper normal limit of normal limits at the screen visit

You drink a lot of alcohol regularly and are not seeking treatment for it.

I agree to use contraception or abstain from sex.

Exclusion Criteria

I have serious blood disorders.

I am taking medication that affects blood clotting.

You are seeking treatment for a problem with alcohol.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive alirocumab or placebo injections and undergo various assessments including blood and urine samples, FibroScans, MRI scans, Doppler scans, ultrasounds, and electrocardiograms.

8 weeks

9 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of treatment-emergent adverse events and changes in biomarkers.

4 weeks

Treatment Details

Interventions

• Alirocumab
• Placebo

Trial Overview The trial is testing alirocumab's safety and effects on the liver in heavy drinkers. Participants will receive either alirocumab or a placebo via injection and undergo various scans, blood tests, heart function tests, surveys about their well-being and drinking habits, as well as discussions about their alcohol consumption.

Participant Groups

Group I: Intervention Experimental Treatment 1 Intervention

Heavy drinking healthy volunteers

Group II: Placebo Placebo Group 1 Intervention

Heavy drinking healthy volunteers

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

Approved in European Union as Praluent for:

• High cholesterol - Familial Homozygous
• Cardiovascular Risk Reduction
• High cholesterol - Familial Heterozygous
• High Cholesterol

Approved in United States as Praluent for:

• High cholesterol - Familial Homozygous
• Cardiovascular Risk Reduction
• High cholesterol - Familial Heterozygous
• Primary hyperlipidemia

Who Is Running the Clinical Trial?

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Lead Sponsor

Trials

865

Recruited

1,091,000+

Findings from Research

Alcohol use disorder (AUD) is common but often under-treated, with only three approved medications, highlighting the need for more diverse and effective treatment options.

The review discusses various pharmacotherapies, including both approved and novel agents, showing promise for improving treatment efficacy and supporting personalized medicine approaches for individuals with AUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Agents for the Pharmacological Treatment of Alcohol Use Disorder. Burnette, EM., Nieto, SJ., Grodin, EN., et al.[2022]

Medications approved for treating alcohol use disorder (AUD), such as naltrexone and acamprosate, have shown consistent small to moderate effects in reducing alcohol consumption, but are often underutilized in clinical practice.

Pharmacogenetic approaches to personalize medication selection based on genetic makeup are promising but have not yet provided strong enough evidence for routine use in treating AUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medications for treating alcohol use disorder: A narrative review. Kranzler, HR., Hartwell, EE.[2023]

Current medications for alcohol use disorders (AUDs) have low response rates, highlighting the need for personalized medicine approaches that consider genetic factors to improve treatment efficacy and safety.

This review discusses the pharmacotherapy of AUDs, including medications like disulfiram, acamprosate, and naltrexone, and emphasizes the importance of pharmacogenetic findings to tailor treatments based on individual patient profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacogenetics of alcohol use disorders and comorbid psychiatric disorders. Helton, SG., Lohoff, FW.[2018]

Alcohol Use Disorder (AUD) affects over 76 million people globally, and current FDA-approved treatments are largely ineffective, highlighting the need for new therapeutic options.

The study employs two rodent drinking models—two-bottle choice (TBC) and drinking in the dark (DID)—to evaluate the effectiveness of new anti-alcohol compounds, providing a rapid and efficient way to screen potential treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Murine Drinking Models in the Development of Pharmacotherapies for Alcoholism: Drinking in the Dark and Two-bottle Choice. Huynh, N., Arabian, NM., Asatryan, L., et al.[2022]

In a 12-week study involving 378 adults with alcohol dependence, those taking nalmefene as needed significantly reduced their heavy drinking days by an average of 13.1 days per month, demonstrating its efficacy in lowering alcohol consumption.

The treatment was well tolerated, with common side effects including nausea (18.3%) and dizziness (17.7%), indicating that nalmefene can be a safe option for managing alcohol dependence in primary care settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nalmefene, Given as Needed, in the Routine Treatment of Patients with Alcohol Dependence: An Interventional, Open-Label Study in Primary Care. Castera, P., Stewart, E., Großkopf, J., et al.[2019]

References

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

Novel Agents for the Pharmacological Treatment of Alcohol Use Disorder. [2022]

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

Medications for treating alcohol use disorder: A narrative review. [2023]

3. Ireland pubmed.ncbi.nlm.nih.gov

Pharmacogenetics of alcohol use disorders and comorbid psychiatric disorders. [2018]

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

Murine Drinking Models in the Development of Pharmacotherapies for Alcoholism: Drinking in the Dark and Two-bottle Choice. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Nalmefene, Given as Needed, in the Routine Treatment of Patients with Alcohol Dependence: An Interventional, Open-Label Study in Primary Care. [2019]