Safety, Tolerability, and Bioeffects of Alirocumab in Non-treatment Seeking Heavy Drinkers

This is an interventional basic science trial for Alcohol Associated Liver Disease focused on measuring Alcohol, Liver, PCSK9, Fatty Liver, Inflammation Read More

• INCLUSION CRITERIA:

  1. Male or female between the age of 21 and 65 years.
  2. Ability to provide written informed consent.

  3. 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.

  4. Current chronic alcohol use, non-treatment seeking heavy drinker (>20 standard drinks per week for at least 12 weeks).
  5. Alanine aminotransferase and/or aspartate aminotransferase and/or gamma-glutamyl transferase exceeding the upper normal limit of normal limits at the screen visit.

EXCLUSION CRITERIA:

1. Treatment seeking for alcohol use disorder.
2. History of a serious hypersensitivity reaction to PCSK9 inhibitors, monoclonal antibodies, or any component of the drug product.
3. 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.
4. Current/past use of PCSK9 inhibitors.
5. Clinically significant and/or unstable cardiovascular-disease over the past 12 months.
6. 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.
7. Positive HIV test or positive Hepatitis B surface antigen (HBsAg), and/or positive Hepatitis C antibody (HCV) at the screening visit.
8. 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, or glomerular filtration rate (GFR) <30ml/min) at screening will be excluded.
9. Triglycerides > 400mg/dL (>4.52 mmol/L) at screening.
10. Chronic renal failure as estimated by glomerular filtration rate (GFR) < 60mL/min/1.73 m^2 at screening.
11. Any underlying clinically significant and/or unstable acute or chronic liver disease unrelated to alcohol use at screening.
12. Patients with coagulopathy defined as INR >1.5, prothrombin time prolonged by > 3s, and/or platelets <75,000 / mm^3 at screening.
13. Use of any medications that interfere with blood clotting.
14. Patients with significant hematologic abnormalities.
15. Significant obesity (Obesity Class III) defined as BMI greater than or equal to 40.
16. History of previous bariatric surgery or transplant surgery.
17. History of plasmapheresis treatment within 2 months prior to screening or plans to undergo plasmapheresis during the study.
18. 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.
19. Use of any investigational drugs within 1 month, or five half-lives, whichever is longer, of the study procedures.
20. Plan to use red yeast rice during the study.
21. Presence of any current or past DSM-5 diagnosis of bipolar disorder or psychotic disorder (e.g. schizophrenia, schizoaffective disorders) or current suicidality.
22. History of epilepsy or alcohol-related seizures in the last 12 months.
23. 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).