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.
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).
Current chronic alcohol use, non-treatment seeking heavy drinker (an average of >= 20 standard drinks per week for at least 12 weeks).
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.
Parallel
Alirocumab
DrugAlirocumab 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.
Placebo
Other interventionHeavy drinking healthy volunteers
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.
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.
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