Alcohol Associated Liver DiseasePhase 1NCT04781322
Safety, Tolerability, and Bioeffects of Alirocumab in Non-treatment Seeking Heavy Drinkers
A Phase 1 study testing Alirocumab in people with Alcohol Associated Liver Disease and Heavy Drinking Behavior, run by National Institute on Alcohol Abuse and Alcoholism (NIAAA) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 21 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Alcohol Associated Liver Disease, Heavy Drinking Behavior
- What is being tested?
- Alirocumab
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Oct 2021to 31 Dec 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male or female between the age of 21 and 65 years.
- Ability to provide written informed consent.
- Females: Negative urine pregnancy test, not currently breastfeeding, agree to abstain or use accepted form of contraception including use of oral contraceptives; use of barrier method of contraceptive, such as condoms; use of an approved IUD or other long-acting reversible contraceptive (LARC); have a male sexual partner who is surgically sterilized; or have exclusively female sexual partner(s).
- Males: Agree to abstain or use accepted form of contraception, such as condoms.
- Current chronic alcohol use, non-treatment seeking heavy drinker (an average of >= 20 standard drinks per week for at least 12 weeks).
Who cannot join
- Treatment seeking for alcohol use disorder.
- History of a serious hypersensitivity reaction to PCSK9 inhibitors, monoclonal antibodies, or any component of the drug product.
- Chronic use of statins within eight weeks of the study to treat hypercholesteremia, or fibrates, with the exception of fenofibrates, within six weeks of the study.
- Current/past use of PCSK9 inhibitors.
- Clinically significant and/or unstable cardiovascular-disease over the past 12 months.
- Current or prior history of any clinically significant disease, including, fibromyalgia, severe neuropathic pain, seizure disorder, uncontrolled endocrine disease known to influence serum lipids or lipoproteins, hemorrhagic stroke, cancer within the past 5 years (except for adequately treated basal skin cancer, squamous cell skin cancer, or in situ cervical cancer), uncontrolled (defined as Hgb A1c >8%) or newly diagnosed (within 3 months prior to screening) diabetes, or any other significant abnormality identified at the time of screening that, in the judgment of the investigator or study clinician, would preclude safe completion of the study.
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- Positive HIV test or positive Hepatitis B surface antigen (HBsAg), and/or positive Hepatitis C antibody (HCV) at screening.
- Alanine aminotransferase or aspartate aminotransferase exceeding 5 times the upper limit of normal levels at screening will be excluded. Bilirubin 2x UNL or Creatinine > 1.5 mg/dl at screening will be excluded.
- Triglycerides > 400mg/dL (>4.52 mmol/L) at screening.
- Chronic renal failure as estimated by glomerular filtration rate (GFR) < 60mL/min/1.73 m^2 at screening.
- Any underlying clinically significant and/or unstable acute or chronic liver disease unrelated to alcohol use at screening.
- Patients with coagulopathy defined as INR >1.5, prothrombin time prolonged by > 3s, and/or platelets <75,000 / mm^3 at screening.
- Use of any medications that interfere with blood clotting.
- Patients with significant hematologic abnormalities.
- Significant obesity (Obesity Class III) defined as BMI greater than or equal to 40 at screening.
- History of previous bariatric surgery or transplant surgery.
- History of plasmapheresis treatment within 2 months prior to screening or plans to undergo plasmapheresis during the study.
- Use of the following medications: Any medication that requires intramuscular administration injections. Systemic corticosteroids, unless used as replacement therapy for pituitary/adrenal disease with a stable regimen for at least 6 weeks prior to screening. Estrogen or testosterone therapy, unless regimen stable for 6 weeks prior to screening visit.
- Use of any investigational drugs within 1 month, or five half-lives, whichever is longer, of the study procedures.
- Plan to use red yeast rice during the study.
- Presence of any current suicidality.
- History of epilepsy or alcohol-related seizures in the last 12 months.
- Any other severe condition, which in the opinion of the investigators would impede the patient s participation or compliance in the study, such as psychosis, delirium or acute change of mental status.
- For optional MRI: a) Presence of ferromagnetic objects in the body that may be adversely affected by or contraindicated for MRI, fear of enclosed spaces, or other standard contraindication to MRI, as determined by self-report b) Use of MRI-incompatible intrauterine device (IUD).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY8664111010, prpl@cc.nih.gov
About this study
Official title: A Phase I, Randomized, Double-Blind, Placebo-Controlled, Study of Safety, Tolerability, and Bioeffects of Alirocumab in Non-treatment Seeking Heavy Drinkers
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.
Read more
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.
Read the detailed description
Study Description:
The PCSK9 inhibitor alirocumab has been recently shown to attenuate alcohol-induced hepatic triglyceride accumulation, hepatocellular injury and hepatic inflammation in a rat model of chronic alcohol exposure. Given the unmet clinical need for novel treatment options for alcohol-associated liver disease (ALD), we are proposing to conduct a safety and tolerability study of alirocumab in this new target population.
We hypothesize that alirocumab will be well tolerated and safe in this new target population and alirocumab will attenuate alcohol-induced liver damage and inflammatory biomarkers.
Objectives:
Primary Objective: The primary objective is to assess the safety and tolerability of alirocumab in subjects who are heavy drinkers.
Secondary/Exploratory Objectives: Secondary/exploratory objectives are to assess various biomarkers related to alcohol-induced liver damage and inflammation.
Endpoints:
Primary Endpoint: 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 with alirocumab or placebo. [Time Frame: baseline to week 8]
Secondary/exploratory Endpoints: The secondary endpoint is to explore effects of alirocumab on various biomarkers using change from baseline.
- Being tested
- Alirocumab, Placebo
- Keywords
- Alcohol, Liver, PCSK9, Fatty Liver, Inflammation
- Medical subject headings
- Fatty Liver, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlirocumabDrug
Alirocumab is a human monoclonal antibody (IgG1) that binds to and inhibits PCSK9 and was approved by the FDA in July of 2015. PCSK9 binds to and promotes degradation of low-density lipoprotein receptors (LDLR) on hepatocyte membranes.
PlaceboOther
Heavy drinking healthy volunteers
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | Heavy drinking healthy volunteers Receives: Drug: Alirocumab |
| Placebo | Placebo comparator | Heavy drinking healthy volunteers Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary objective is to assess the safety and tolerability of alirocumab in subjects who are heavy drinkers.
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 with alirocumab or placebo.
Measured: 8 weeks
Secondary outcomes (1)
Secondary/exploratory objectives are to assess various biomarkers related to alcohol-induced liver damage and inflammation.
These biomarkers will assess various biological processed in AUD, such as inflammation, liver biology and clinical alcohol-related outcomes.
Measured: ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2021
- Study start19 Oct 2021
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alcohol Associated Liver DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Falk W Lohoff, M.D., Principal investigator, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04781322
- Sponsor's protocol ID
- 10000036
- Other IDs
- 000036-AA
- Status last verified
- 16 Jul 2026
- First submitted
- 3 Mar 2021
- Last updated
- 20 Jul 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Randomized, Double-Blind, Placebo-Controlled, Study of Safety, Tolerability, and Bioeffects of Alirocumab in Non-treatment Seeking Heavy Drinkers
- ClinicalTrials.gov ID
- NCT04781322
- Acronym / sponsor ID
- 10000036
- Keywords
- Alcohol, Liver, PCSK9, Fatty Liver, Inflammation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)US National Institutes of Health
- Study start
- 19 Oct 2021 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 4 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Study Description:
The PCSK9 inhibitor alirocumab has been recently shown to attenuate alcohol-induced hepatic triglyceride accumulation, hepatocellular injury and hepatic inflammation in a rat model of chronic alcohol exposure. Given the unmet clinical need for novel treatment options for alcohol-associated liver disease (ALD), we are proposing to conduct a safety and tolerability study of alirocumab in this new target population.
We hypothesize that alirocumab will be well tolerated and safe in this new target population and alirocumab will attenuate alcohol-induced liver damage and inflammatory biomarkers.
Objectives:
Primary Objective: The primary objective is to assess the safety and tolerability of alirocumab in subjects who are heavy drinkers.
Secondary/Exploratory Objectives: Secondary/exploratory objectives are to assess various biomarkers related to alcohol-induced liver damage and inflammation.
Endpoints:
Primary Endpoint: 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 with alirocumab or placebo. [Time Frame: baseline to week 8]
Secondary/exploratory Endpoints: The secondary endpoint is to explore effects of alirocumab on various biomarkers using change from baseline.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Drug: AlirocumabHeavy drinking healthy volunteers |
| Placebo | Placebo comparator | Other: PlaceboHeavy drinking healthy volunteers |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Males: Agree to abstain or use accepted form of contraception, such as condoms.
Key exclusion criteria (24 listed)
- Treatment seeking for alcohol use disorder.
- History of a serious hypersensitivity reaction to PCSK9 inhibitors, monoclonal antibodies, or any component of the drug product.
- Chronic use of statins within eight weeks of the study to treat hypercholesteremia, or fibrates, with the exception of fenofibrates, within six weeks of the study.
- Current/past use of PCSK9 inhibitors.
- Clinically significant and/or unstable cardiovascular-disease over the past 12 months.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlirocumabAlirocumab is a human monoclonal antibody (IgG1) that binds to and inhibits PCSK9 and was approved by the FDA in July of 2015. PCSK9 binds to and promotes degradation of low-density lipoprotein receptors (LDLR) on hepatocyte membranes. | Drug | Intervention |
| PlaceboHeavy drinking healthy volunteers | Other | Placebo |
Primary outcome
The primary objective is to assess the safety and tolerability of alirocumab in subjects who are heavy drinkers.
Time frame: 8 weeks
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 with alirocumab or placebo.
1 secondary outcome
Secondary/exploratory objectives are to assess various biomarkers related to alcohol-induced liver damage and inflammation.
Time frame: ongoing
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Falk W Lohoff, M.D. principal investigator
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Alirocumab in people with Alcohol Associated Liver Disease and Heavy Drinking Behavior, run by National Institute on Alcohol Abuse and Alcoholism (NIAAA) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nada M Saleh ((301) 496-3799, nada.saleh@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary objective is to assess the safety and tolerability of alirocumab in subjects who are heavy drinkers. (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2026.