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Protocol Details

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 currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

000036-AA

Sponsoring Institute

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 21 Years
Max Age: 65 Years

Referral Letter Required

No

Population Exclusion(s)

Children

Keywords

Alcohol;
Liver;
PCSK9;
Fatty Liver;
Inflammation

Recruitment Keyword(s)

None

Condition(s)

Alcohol associated Liver disease;
Heavy Drinking Behavior

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

Drug: Alirocumab
Other: Placebo

Supporting Site

National Institute on Alcohol Abuse and Alcoholism

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.

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Eligibility

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 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 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 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).


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Citations:

Not Provided

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Contacts:

Principal Investigator

Referral Contact

For more information:

Falk W. Lohoff, M.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
NIHBC 10 - CRC BG RM 2-2330
10 CENTER DR
BETHESDA MD 20892
(301) 827-1542
falk.lohoff@nih.gov

Nada M. Saleh
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institutes of Health
Building 60
Room 265
60 Cloister Court
Bethesda, Maryland 20892
(301) 435-9376
nada.saleh@nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1
ccopr@nih.gov

Clinical Trials Number:

NCT04781322

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