Effects of alirocumab on liver health in heavy drinkers
A Phase I, Randomized, Double-Blind, Placebo-Controlled, Study of Safety, Tolerability, and Bioeffects of Alirocumab in Non-treatment Seeking Heavy Drinkers
This study is testing if the drug alirocumab is safe for heavy drinkers aged 21 to 65 and if it can help improve their liver health.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 100 (estimated) |
| Ages | 21 Years to 65 Years |
| Sex | All |
| Sponsor | National Institutes of Health Clinical Center (CC) NIH |
| Drugs / interventions | alirocumab |
| Locations | 1 site (Bethesda, Maryland) |
| Trial ID | NCT04781322 on ClinicalTrials.gov |
What this trial studies
This study investigates the safety and tolerability of alirocumab, a PCSK9 inhibitor, in non-treatment seeking heavy drinkers aged 21 to 65 who consume an average of 20 or more alcoholic drinks per week. Participants will receive either alirocumab or a placebo via injection and undergo various assessments including blood and urine tests, physical exams, and imaging studies to evaluate liver function and inflammation. The primary goal is to determine the incidence of adverse events, while secondary objectives will explore changes in biomarkers related to liver damage and inflammation.
Who should consider this trial
Good fit: Ideal candidates are healthy adults aged 21 to 65 who are non-treatment seeking heavy drinkers consuming 20 or more drinks per week.
Not a fit: Patients seeking treatment for alcohol use disorder may not benefit from this study.
Why it matters
Potential benefit: If successful, this study could provide a novel treatment option for individuals with alcohol-associated liver disease.
How similar studies have performed: While the approach of using alirocumab in this context is novel, previous studies have shown its potential to reduce liver damage in animal models.
Eligibility criteria
Show full inclusion / exclusion criteria
* 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 (an average of \>= 20 standard drinks per week for at least 12 weeks).
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 screening.
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 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 at screening.
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 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).
Where this trial is running
Bethesda, Maryland
- National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)
Study contacts
- Principal investigator: Falk W Lohoff, M.D. — National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Study coordinator: Nada M Saleh
- Email: nada.saleh@nih.gov
- Phone: (301) 496-3799
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.