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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how alirocumab, a cholesterol-lowering medication, affects liver health in people who consume alcohol. Researchers seek to determine if alirocumab can reduce liver swelling or injury from alcohol consumption. Participants will receive either the drug or a placebo via injection, and various tests will assess liver function and overall health. The study seeks healthy adults who regularly consume 20 or more alcoholic drinks per week. Participants will undergo several health assessments and meetings over 8 weeks. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

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.

Is there any evidence suggesting that alirocumab is likely to be safe for humans?

Research has shown that alirocumab is generally safe for people. One study found that participants taking alirocumab experienced about the same number of side effects as those taking a placebo, a harmless pill. However, those receiving alirocumab reported more injection site reactions, such as redness or swelling.

Animal studies suggest that alirocumab might reduce some harmful effects of alcohol, like stress on the brain, potentially protecting the liver and brain from alcohol-related damage.

Since this trial is in an early stage, the main goal is to assess the safety of alirocumab. Researchers are closely monitoring for any side effects. Although alirocumab is already approved for other uses, this trial is crucial to confirm its safety specifically for people who drink heavily. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for Alcohol Use Disorder focus on behavioral therapy or medications like naltrexone and acamprosate that target the brain's reward system. But alirocumab works differently, targeting cholesterol levels by inhibiting a protein called PCSK9. This unique mechanism might reduce cravings linked to alcohol consumption. Researchers are excited because this approach offers a fresh angle and could open up new pathways for managing Alcohol Use Disorder, especially for those who haven’t had success with traditional methods.

What evidence suggests that alirocumab might be an effective treatment for alcohol use disorder?

Research suggests that alirocumab, which participants in this trial may receive, might help with liver problems related to alcohol use. Studies have shown that alirocumab can lessen alcohol's harmful effects on the liver by lowering a protein called PCSK9, which can increase with alcohol use. This reduction may improve liver function by boosting the activity of certain receptors that help control cholesterol levels. Additionally, earlier research found that alirocumab reduces cell damage and improves brain health in heavy drinkers. While these findings are promising, they are based on early research, so more studies are needed to confirm these effects in people. ^{1 2 4 6 7}

Who Is on the Research Team?

Falk W Lohoff, M.D.

Principal Investigator

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01288443

Study Details | NCT01288443 | Efficacy and Safety ... Primary Objective: To evaluate the effect of alirocumab (SAR236553/REGN727) on low-density lipoprotein cholesterol (LDL-C) levels after 12 weeks of ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6868240/

PCSK9 inhibition as a novel therapeutic target for alcoholic ... Alirocumab treatment also attenuated alcohol-induced PCSK9 mRNA elevation and upregulated LDL-receptor (LDL-R) via modulation of the ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0889159124003702

PCSK9 inhibition attenuates alcohol-associated neuronal ... This study presents novel evidence that alirocumab diminishes oxidative stress and modifies neuroimmune interactions in the brain elicited by chronic ethanol ...

4. nature.com nature.com/articles/s41598-019-53603-6

PCSK9 inhibition as a novel therapeutic target for alcoholic ... Alirocumab treatment also attenuated alcohol-induced PCSK9 mRNA elevation and upregulated LDL-receptor (LDL-R) via modulation of the ...

5. link.springer.com link.springer.com/article/10.1007/s40801-024-00471-w

Lipid-Lowering Efficiency and Safety of Alirocumab 300 mg ... The ODYSSEY CHOICE I trial showed an LDL-C reduction after 12 weeks by 52.7% in patients receiving alirocumab 300 mg Q4W without concomitant ...

6. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT04781322

Safety, Tolerability, and Bioeffects of Alirocumab in Non- ... The primary endpoint in the study is to assess the incidence and severity of treatment-emergent adverse events in non-treatment seeking heavy drinkers treated ...

7. pro.campus.sanofi pro.campus.sanofi/uk/dyslipidaemia/articles/odyssey-outcomes-safety-praluent

ODYSSEY OUTCOMES Safety Profile Praluent® ... Patients treated with Praluent experienced a similar frequency of adverse events to those on placebo, but with more local injection site reactions.