Clinical trial NCT02046200: Development of Ivermectin for Alcohol Use Disorders
Official title: Repositioning Ivermectin for the Treatment of Alcohol Use Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Alcohol Use Disorder
Keywords: ivermectin, alcoholism, alcohol use disorder, treatment
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
First posted: 2014-01-27
Enrollment: 11
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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.

Primary outcomes:
measure: Heart Rate
timeFrame: Post-medication administration (hours): 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48; During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl
measure: Systolic Blood Pressure
timeFrame: Post-medication administration (hours): 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48; During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl
measure: Diastolic Blood Pressure
timeFrame: Post-medication administration (hours): 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48; During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl
measure: Subjective Effects of Alcohol Using the Alcohol Urge Questionnaire (AUQ)
timeFrame: During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours.
measure: Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - "Feel" Subscale
timeFrame: During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours.
measure: Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - "Like" Subscale
timeFrame: During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours.
measure: Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - "More" Subscale
timeFrame: During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours.
measure: Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - "High" Subscale
timeFrame: During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours.
measure: Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Stimulant Subscale
timeFrame: During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours.
measure: Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Sedative Subscale
timeFrame: During alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl period; which is expected to last approximately 6 hours.
measure: Cue-induced Craving Using the Alcohol Urge Questionnaire (AUQ)
timeFrame: 6 hours post-medication administration
measure: Adverse Effects
timeFrame: During alcohol infusion at BrAC = 0.00, 0.04, 0.08 g/dl
Secondary outcomes:
measure: Ivermectin Pharmacokinetics: Peak Concentration (Cmax)
timeFrame: Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48
measure: Ivermectin Pharmacokinetics: Time to Cmax (Tmax)
timeFrame: Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48
measure: Ivermectin Pharmacokinetics: Area Under the Time-concentration Curve (AUC)
timeFrame: Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48
measure: Ivermectin Pharmacokinetics: Half-life (T1/2)
timeFrame: Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48
measure: Stress-induced Alcohol Craving
timeFrame: pre-post exposure to an imaginal stress script
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Addictions Laboratory
state: California
Study officials:
affiliation: University of California, Los Angeles
name: Lara Ray, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Los Angeles
name: Daniel Roche, PhD
role: STUDY_DIRECTOR
References: