Clinical Trial: Development of Ivermectin for Alcohol Use Disorders

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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 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. 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.
Sponsor: University of California, Los Angeles

Current Primary Outcome:

  • 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.

  • 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.

  • 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

    Original Primary Outcome:

    • Heart rate, blood pressure (Safety) [ 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 and blood pressure will be monitored to determine the safe of combining IVM (30 mg) with moderate doses of alcohol (0.08 g/dl).

      During the infusion, the times for collecting HR/BP will vary based on how long it takes participants to reach the targeted BrACs.

    • Subjective effects using the Alcohol urge questionnaire (AUQ), Drug Effects Questionnaire, and Biphasic Alcohol Effects Scale (BAES) [ Time Frame: during the alcohol infusion and observation; 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) [ Time Frame: 5.5 hours post-medication administration; 6 hours post-medication administration ]
    • Adverse effects scores on the SAFTEE [ 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 ]

      Side effects will be monitored to determine the safe of combining IVM (30 mg) with moderate doses of alcohol (0.08 g/dl).

      During the infusion, the times for collecting HR/BP will vary based on how long it takes participants to reach the targeted BrACs.



    Current Secondary Outcome:

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


    Original Secondary Outcome:

    • Stress-induced Alcohol Craving [ Time Frame: pre-post exposure to an imaginal stress script ]
      Alcohol Urge Questionnaire (AUQ) Profile of Mood States (POMS)
    • 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 also collect blood samples for pharmacokinetic (PK) and pharmacodynamic profiling in order to examine whether IVM metabolism corresponds to its effects on alcohol response.
    • 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 ]
    • 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 ]
    • Ivermectin pharmacokinetics: half-life [ Time Frame: Hours post-drug administration: 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 48 ]


    Information By: University of California, Los Angeles

    Dates:
    Date Received: January 14, 2014
    Date Started: February 2014
    Date Completion:
    Last Updated: March 1, 2017
    Last Verified: March 2017