Development of Ivermectin for Alcohol Use Disorders

Condition(s) targeted: Alcohol Use Disorder

Intervention: Ivermectin (Drug); Placebo (Drug); Alcohol (Drug)

Phase: Phase 1/Phase 2

Status: Completed

Sponsored by: University of California, Los Angeles

Official(s) and/or principal investigator(s):
Lara Ray, PhD, Principal Investigator, Affiliation: University of California, Los Angeles
Daniel Roche, PhD, Study Director, Affiliation: University of California, Los Angeles

Current pharmacotherapies for alcohol use disorders (AUDs) have limited efficacy. Thus, the development of effective treatments for AUDs represents an important public health objective. Repositioning, i. e. using existing approved drugs for other indications, represents a fast and economically feasible approach for drug development. Ivermectin (IVM) is an FDA-approved antiparasitic medication that can significantly reduce alcohol intake in mice, suggesting that it may be useful in the treatment of AUDs in humans. The goal of this project is to provide key clinical evidence that IVM can be repositioned as a novel therapeutic agent to treat AUDs.

Official title: Repositioning Ivermectin for the Treatment of Alcohol Use Disorders

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome:

Heart rate, blood pressure (Safety)

Subjective effects using the Alcohol urge questionnaire (AUQ), Drug Effects Questionnaire, and Biphasic Alcohol Effects Scale (BAES)

Cue-induced craving using the Alcohol Urge Questionnaire (AUQ)

Adverse effects scores on the SAFTEE

Secondary outcome:

Stress-induced alcohol craving

Ivermectin pharmacokinetics: peak concentration (Cmax)

Ivermectin pharmacokinetics: time to Cmax (Tmax)

Ivermectin pharmacokinetics: area under the time-concentration curve (AUC)

Ivermectin pharmacokinetics: half-life

Detailed description: Current pharmacotherapies for alcohol use disorders (AUDs) have limited efficacy. Thus, the development of effective treatments for AUDs represents an important public health objective. Repositioning, i. e. using existing approved drugs for other indications, represents a fast and economically feasible approach for drug development. Ivermectin (IVM) is an FDA-approved antiparasitic medication that can significantly reduce alcohol intake in mice, suggesting that it may be useful in the treatment of AUDs in humans. The goal of this project is to provide key clinical evidence that IVM can be repositioned as a novel therapeutic agent to treat AUDs. We will enroll 10 alcohol dependent individuals in a placebo-controlled randomized pilot safety trial of IVM (30 mg orally once) over a 2-day (1-night) inpatient stay at the UCLA CTRC and employ a well-characterized battery of behavioral paradigms (i. e., alcohol administration and cue exposure). The goals of the study are to test: (a) the safety of combining IVM, at a dose currently shown to be safe in humans (30 mg), with moderate doses of alcohol (0. 08 g/dl); and (b) whether IVM reduces the reinforcing effects of alcohol during alcohol administration and whether it reduces alcohol craving during cue exposure, as compared to placebo.

Minimum age: 21 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- age between 21 and 65;

- meet current DSM-V diagnostic criteria for an alcohol use disorder

Exclusion Criteria:

- current treatment for alcohol problems, a history of treatment in the 30 days before

enrollment or current treatment seeking;

- a current (last 12 months) DSM-V diagnosis of dependence on any psychoactive

substances other than alcohol and nicotine;

- a lifetime DSM-IV diagnosis of schizophrenia, bipolar disorder, or any psychotic

disorder;

- positive urine screen for narcotics, amphetamines, or sedative hypnotics;

- serious alcohol withdrawal symptoms as indicated by a score ≥ 10 on the Clinical

Institute Withdrawal Assessment for Alcohol-Revised (CIWA-R);

- pregnancy, nursing, or refusal to use reliable method of birth control (if female);

- a medical condition that may interfere with safe study participation (e. g., unstable

cardiac, renal, or liver disease, uncontrolled hypertension or diabetes);

- AST, ALT, or GGT ≥ 3 times upper normal limit;

- currently on prescription medication that contraindicates use of IVN;

- any other circumstances that, in the opinion of the investigators, compromises

participant safety.

UCLA Addictions Laboratory, Los Angeles, California 90095, United States

UCLA Addictions Laboratory

Starting date: February 2014
Last updated: August 18, 2015