Alirocumab for Alcohol Use Disorder

Recruiting in Palo Alto (17 mi)

Overseen by Falk W Lohoff, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

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

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

Disqualifiers: Cardiovascular disease, Diabetes, Cancer, others

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.

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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.

Trial 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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

National Institutes of Health Clinical Center Bethesda, MD

Who Is Running the Clinical Trial?

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

References

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

Novel Agents for the Pharmacological Treatment of Alcohol Use Disorder. [2022] Alcohol use disorder (AUD) is a highly prevalent but severely under-treated disorder, with only three widely-approved pharmacotherapies. Given that AUD is a very heterogeneous disorder, it is unlikely that one single medication will be effective for all individuals with an AUD. As such, there is a need to develop new, more effective, and diverse pharmacological treatment options for AUD with the hopes of increasing utilization and improving care. In this qualitative literature review, we discuss the efficacy, mechanism of action, and tolerability of approved, repurposed, and novel pharmacotherapies for the treatment of AUD with a clinical perspective. Pharmacotherapies discussed include: disulfiram, acamprosate, naltrexone, nalmefene, topiramate, gabapentin, varenicline, baclofen, sodium oxybate, aripiprazole, ondansetron, mifepristone, ibudilast, suvorexant, prazosin, doxazosin, N-acetylcysteine, GET73, ASP8062, ABT-436, PF-5190457, and cannabidiol. Overall, many repurposed and novel agents discussed in this review demonstrate clinical effectiveness and promise for the future of AUD treatment. Importantly, these medications also offer potential improvements towards the advancement of precision medicine and personalized treatment for the heterogeneous AUD population. However, there remains a great need to improve access to treatment, increase the menu of approved pharmacological treatments, and de-stigmatize and increase treatment-seeking for AUD.

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

Medications for treating alcohol use disorder: A narrative review. [2023] Chronic heavy alcohol use impacts all major neurotransmitter systems and is associated with multiple medical, psychiatric, and social problems. Available evidence-based medications to treat alcohol use disorder (AUD) are underutilized in clinical practice. These medications promote abstinence or reduce alcohol consumption, though there are questions regarding their optimal dosage, length of treatment, and utility in combination with one another. Pharmacogenetic approaches, which use a patient's genetic make-up to inform medication selection, have garnered great interest but have yet to yield results robust enough to incorporate them in routine clinical care. This narrative review summarizes the evidence both for medications approved by the Food and Drug Administration (disulfiram, oral naltrexone, acamprosate, and extended-release naltrexone) and those commonly used off-label (e.g., gabapentin, baclofen, and topiramate) for AUD treatment. We discuss these drugs' mechanisms of action, clinical use, pharmacogenetic findings, and treatment recommendations. We conclude that the most consistent evidence supporting the pharmacotherapy of AUD is for the opioid antagonists, naltrexone and nalmefene (which is not approved in the United States), and topiramate. These medications demonstrate consistent small or moderate effects in reducing the frequency of drinking and/or heavy drinking. Lastly, we make suggestions for research needed to refine and expand the current literature on effective pharmacotherapy for AUD.

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

Pharmacogenetics of alcohol use disorders and comorbid psychiatric disorders. [2018] Alcohol use disorders (AUDs) represent a significant health burden worldwide. Currently, there are three medications approved by the U.S. Food and Drug Administration for the treatment of AUDs, and other drugs are being prescribed off-label for this purpose. However, response rates for pharmacologic treatment are low, and extant research suggests that treatment effects may partially depend on genetic factors. Personalized medicine, or using a patient's genetics and/or personal history to determine efficacy of treatment prior to prescription, is an emerging tool that will help clinicians treat their patients more effectively and safely. This review systematically discusses current findings from AUD pharmacotherapy trials examining disulfiram, acamprosate, naltrexone, the injectable naltrexone, and topiramate. Furthermore, it presents pharmacogenetics findings associated with these medications in an attempt to further the field of personalized medicine. Research from trials examining AUDs and comorbid major depressive disorder and anxiety disorders is also presented, and pharmacogenetic findings for these treatments are discussed. Lastly, the authors comment on the present and future states of the field of personalized medicine for AUD.

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] Alcohol Use Disorder (AUD) is a major problem with more than an estimated 76 million people worldwide meeting the diagnostic criteria. Current treatments are limited to three FDA-approved medications that are largely ineffective even when combined with psychosocial intervention, as is evident by the high relapse rate. As such, the search for more novel treatments represents an important public health goal. To this end, the following protocol utilizes two simple rodent drinking models to assess the preclinical efficacy of lead anti-alcohol compounds: two-bottle choice (TBC) and drinking in the dark (DID). The former allows mice to voluntary drink in moderation while the latter induces mice to voluntary consume a large amount of alcohol in a short period that mimics binge drinking. The simple and high throughput nature of both of these paradigms allow for rapid screening of pharmacological agents or for identifying strains of mice that exhibit certain voluntary drinking behavior.

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] This 12-week, open-label, primary care study (NCT02195817) evaluated the efficacy and safety of nalmefene, taken as needed, to reduce alcohol consumption in adults with a diagnosis of alcohol dependence and drinking at least at high drinking risk levels (DRL, > 60 g/day for men, > 40 g/day for women).