Development of Ivermectin for Alcohol Use Disorders

NCT02046200 | Completed Phase 1 Results DMC

• 2 other identifiers: IVMUL1TR000124
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Alcohol Use Disorder

Keywords

ivermectin, alcoholism, alcohol use disorder, treatment

Outcome Measures

Primary Outcomes (12)

• Heart Rate

  Heart rate (measured in beats per minute; BPM) will be monitored to determine the safety of combining IVM (30 mg) with moderate doses of alcohol (0.08 g/dl). During the infusion, the times for collecting HR will vary based on how long it takes participants to reach the targeted BrACs.

  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

• Systolic Blood Pressure

  Blood pressure (measured in mmHg) will be monitored to determine the safety of combining IVM (30 mg) with moderate doses of alcohol (0.08 g/dl). Blood pressure is measured at 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post-medication administration; and during alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl. During the infusion, the times for collecting BP will vary based on how long it takes participants to reach the targeted BrACs.

  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

• Diastolic Blood Pressure

  Blood pressure (measured in mmHg) will be monitored to determine the safety of combining IVM (30 mg) with moderate doses of alcohol (0.08 g/dl). Blood pressure is measured at 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48 hours post-medication administration; and during alcohol infusion at BrAC = 0.00, 0.02, 0.04, 0.06, 0.08 g/dl. During the infusion, the times for collecting BP will vary based on how long it takes participants to reach the targeted BrACs.

  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

• Subjective Effects of Alcohol Using the Alcohol Urge Questionnaire (AUQ)

  Subjective effects of alcohol will be measured using the Alcohol Urge Questionnaire (AUQ), which consists of 8 items associated with urge to drink alcohol, rated on a 7 point scale (1 = strongly disagree, 7 = strongly agree).

  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.

• Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - "Feel" Subscale

  Subjective effects of alcohol will be measured using the Drug Effects Questionnaire, which consists of 4 items that capture subjective effects, (feeling effects, liking effects, wanting more and being high). The question "Do you feel any drug effects?" was rated on an 11 point scale from 0 to 10 (higher values represent more effects).

  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.

• Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - "Like" Subscale

  Subjective effects of alcohol will be measured using the Drug Effects Questionnaire, which consists of 4 items that capture subjective effects, (feeling effects, liking effects, wanting more and being high). The question "Do you like the effects you are feeling right now?" was rated on an 11 point scale from 0 to 10 (higher values represent more effects).

  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.

• Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - "More" Subscale

  Subjective effects of alcohol will be measured using the Drug Effects Questionnaire, which consists of 4 items that capture subjective effects, (feeling effects, liking effects, wanting more and being high). The question "Would you like more of the drug right now?" was rated on an 11 point scale from 0 to 10 (higher values represent more effects).

  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.

• Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - "High" Subscale

  Subjective effects of alcohol will be measured using the Drug Effects Questionnaire, which consists of 4 items that capture subjective effects, (feeling effects, liking effects, wanting more and being high). The question "Are you high?" was rated on an 11 point scale from 0 to 10 (higher values represent more effects).

  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.

• Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Stimulant Subscale

  Subjective effects of alcohol will be measured using the Biphasic Alcohol Effects Scale (BAES) , which consists of 14 items designed to capture the stimulant and sedative effects of alcohol, each rated on an 11-point scale (0 = not at all, 10 = extremely). The total score for the Stimulant Subscale ranges from 0 to 70. Mean scores across all subjects are reported below.

  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.

• Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Sedative Subscale

  Subjective effects of alcohol will be measured using the Biphasic Alcohol Effects Scale (BAES) , which consists of 14 items designed to capture the stimulant and sedative effects of alcohol, each rated on an 11-point scale (0 = not at all, 10 = extremely). The total score for the Sedative Subscale ranges from 0 to 70. Mean scores across subjects are reported below.

  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.

• Cue-induced Craving Using the Alcohol Urge Questionnaire (AUQ)

  Cue-induced craving will be measured using the Alcohol Urge Questionnaire (AUQ), which consists of 8 items associated with urge to drink alcohol, rated on a 7 point scale (0 = strongly disagree, 6 = strongly agree). Item scores were averaged and the total score also ranges from 0-6.

  6 hours post-medication administration

• Adverse Effects

  Adverse effects will be monitored to determine the safe of combining IVM (30 mg) with moderate doses of alcohol (0.08 g/dl) using the Systematic Assessment for Treatment Emergent Effects (SAFTEE). The SAFTEE is a 24-item checklist in which the participant can identify whether a symptom is present (yes/no), its severity (mild, moderate, severe) and whether it was caused by the medication (yes/no). Data below represents a count of individual adverse effects reported on the SAFTEE during the alcohol infusion.

  During alcohol infusion at BrAC = 0.00, 0.04, 0.08 g/dl

Secondary Outcomes (5)

• Ivermectin Pharmacokinetics: Peak Concentration (Cmax)

  Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48

• Ivermectin Pharmacokinetics: Time to Cmax (Tmax)

  Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48

• Ivermectin Pharmacokinetics: Area Under the Time-concentration Curve (AUC)

  Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48

• Ivermectin Pharmacokinetics: Half-life (T1/2)

  Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48

• Stress-induced Alcohol Craving

  pre-post exposure to an imaginal stress script

Study Arms (2)

Ivermectin

EXPERIMENTAL

Ivermectin 30 mg single dose

Drug: Ivermectin; Drug: Alcohol

Sugar pill

PLACEBO COMPARATOR

Matched placebo, single dose

Drug: Placebo; Drug: Alcohol

Interventions

Ivermectin DRUG

Ivermectin is a semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum antiparasitic avermectin.

Also known as: Stromectol

Ivermectin

Placebo DRUG

Matched placebo

Also known as: Sugar pill

Sugar pill

Alcohol DRUG

Also known as: 5% ethanol IV solution

Ivermectin; Sugar pill

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age between 21 and 65;
• meet current DSM-V diagnostic criteria for an alcohol use disorder

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (1)

UCLA Addictions Laboratory

Los Angeles, California, 90095, United States

Location

Related Links

• UCLA Addictions Laboratory

MeSH Terms

Conditions

Alcoholism

Interventions

Ivermectin; Sugars; Ethanol

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Macrolides; Polyketides; Lactones; Organic Chemicals; Carbohydrates; Alcohols

Results Point of Contact

• Title: Dr. Lara Ray
• Organization: UCLA Department of Psychology

lararay@psych.ucla.edu

310-794-5383

Study Officials

• Lara Ray, PhD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

• Daniel Roche, PhD

  University of California, Los Angeles

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 14, 2014
• First Posted: January 27, 2014
• Study Start: February 1, 2014
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: August 8, 2018
• Results First Posted: April 13, 2017

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)