Don't get left behind! The modernized ClinicalTrials.gov is coming. Check it out now.
Say goodbye to ClinicalTrials.gov!
The new site is coming soon - go to the modernized ClinicalTrials.gov
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Development of Ivermectin for Alcohol Use Disorders

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02046200
Recruitment Status : Completed
First Posted : January 27, 2014
Results First Posted : April 13, 2017
Last Update Posted : August 8, 2018
Sponsor:
Information provided by (Responsible Party):
Lara Ray, PhD, University of California, Los Angeles

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
Alcohol Use Disorder Drug: Ivermectin Drug: Placebo Drug: Alcohol Phase 1 Phase 2

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.
Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Repositioning Ivermectin for the Treatment of Alcohol Use Disorders
Study Start Date : February 2014
Actual Primary Completion Date : March 2015
Actual Study Completion Date : March 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Alcohol

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Ivermectin
Ivermectin 30 mg single dose
 Drug: Ivermectin
Ivermectin is a semi-synthetic macrocyclic lactone used worldwide as a broad-spectrum antiparasitic avermectin.
Other Name: Stromectol

Drug: Alcohol
Other Name: 5% ethanol IV solution
Placebo Comparator: Sugar pill
Matched placebo, single dose
 Drug: Placebo
Matched placebo
Other Name: Sugar pill

Drug: Alcohol
Other Name: 5% ethanol IV solution


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Heart Rate [ Time Frame: 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 ]

    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.


  2. Systolic Blood Pressure [ Time Frame: 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 ]

    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.


  3. Diastolic Blood Pressure [ Time Frame: 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 ]

    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.


  4. Subjective Effects of Alcohol Using the Alcohol Urge Questionnaire (AUQ) [ Time Frame: 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 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).

  5. Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - "Feel" Subscale [ Time Frame: 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 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).

  6. Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - "Like" Subscale [ Time Frame: 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 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).

  7. Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - "More" Subscale [ Time Frame: 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 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).

  8. Subjective Effects of Alcohol Using the Drug Effects Questionnaire (DEQ) - "High" Subscale [ Time Frame: 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 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).

  9. Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Stimulant Subscale [ Time Frame: 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 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.

  10. Subjective Effects of Alcohol Using the Biphasic Alcohol Effects Scale (BAES) - Sedative Subscale [ Time Frame: 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 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.

  11. Cue-induced Craving Using the Alcohol Urge Questionnaire (AUQ) [ Time Frame: 6 hours post-medication administration ]
    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.

  12. Adverse Effects [ Time Frame: During alcohol infusion at BrAC = 0.00, 0.04, 0.08 g/dl ]
    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.


Secondary Outcome Measures :
  1. Ivermectin Pharmacokinetics: Peak Concentration (Cmax) [ Time Frame: Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48 ]
    This study will collect blood samples for pharmacokinetic (PK) and pharmacodynamic profiling in order to examine whether IVM metabolism corresponds to its effects on alcohol response. Maximum plasma concentration (Cmax), measured in ng/mL, provided below.

  2. Ivermectin Pharmacokinetics: Time to Cmax (Tmax) [ Time Frame: Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48 ]
    This study will collect blood samples for pharmacokinetic (PK) and pharmacodynamic profiling in order to examine whether IVM metabolism corresponds to its effects on alcohol response. Time to Cmax (Tmax), measured in hours, provided below.

  3. Ivermectin Pharmacokinetics: Area Under the Time-concentration Curve (AUC) [ Time Frame: Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48 ]
    This study will collect blood samples for pharmacokinetic (PK) and pharmacodynamic profiling in order to examine whether IVM metabolism corresponds to its effects on alcohol response. Area under the time-concentration curve (AUC) from 0 to 48 hours after IVM administration, provided below.

  4. Ivermectin Pharmacokinetics: Half-life (T1/2) [ Time Frame: Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48 ]
    This study will collect blood samples for pharmacokinetic (PK) and pharmacodynamic profiling in order to examine whether IVM metabolism corresponds to its effects on alcohol response. Half-life of ivermectin (T1/2), measured in hours, provided below.

  5. Stress-induced Alcohol Craving [ Time Frame: pre-post exposure to an imaginal stress script ]
    Alcohol Urge Questionnaire (AUQ)


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   21 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02046200


Locations
Layout table for location information
United States, California
UCLA Addictions Laboratory
Los Angeles, California, United States, 90095
Sponsors and Collaborators
University of California, Los Angeles
Investigators
Layout table for investigator information
Principal Investigator: Lara Ray, PhD University of California, Los Angeles
Study Director: Daniel Roche, PhD University of California, Los Angeles
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Layout table for additonal information
Responsible Party: Lara Ray, PhD, Associate Professor, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT02046200    
Other Study ID Numbers: IVM
UL1TR000124 ( U.S. NIH Grant/Contract )
First Posted: January 27, 2014    Key Record Dates
Results First Posted: April 13, 2017
Last Update Posted: August 8, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Lara Ray, PhD, University of California, Los Angeles:
ivermectin, alcoholism, alcohol use disorder, treatment
Additional relevant MeSH terms:
Layout table for MeSH terms
Disease
Alcoholism
Alcohol Drinking
Pathologic Processes
Drinking Behavior
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
 Mental Disorders
Ethanol
Ivermectin
Anti-Infective Agents, Local
Anti-Infective Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Antiparasitic Agents