Development of Ibudilast for Alcohol Use Disorder

February 19, 2016 updated by: Lara Ray, University of California, Los Angeles

Development of Ibudilast as a Novel Treatment for Alcohol Dependence

The objective of this proposal is to advance medication development for alcoholism by conducting a safety and initial efficacy study of ibudilast, a neuroimmune modulator and phosphodiesterase inhibitor, for alcohol use disorders.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Alcohol dependence (AD) is a chronic and relapsing condition affecting 10 million Americans. To date, only four pharmacotherapies are approved by the FDA for the treatment of alcoholism and their efficacy is modest. Therefore, medication development for AD represents a high priority area. Ibudilast (IBUD) is a glial cell modulator that inhibits phosphodiesterases (PDE) -4 and -10 and macrophage migration inhibitory factor (MIF). Preclinical data suggest that neuroimmune modulation is critical to the rewarding properties of drugs of abuse, including alcohol. Further, IBUD has been shown to enhance GDNF release in vivo and GDNF modulation has been implicated in alcohol reinstatement in animals, while PDE inhibition has been shown to reduce alcohol intake in mice. Together, these findings suggest that neuroimmune modulation constitutes a novel target for the treatment of alcoholism. The objective of this study is to advance medication development for alcoholism by conducting an initial Phase II study of IBUD for AD. Specifically, the proposed study consists of a randomized, double-blind, placebo-controlled within-subject crossover design to determine the safety, tolerability, and initial human laboratory efficacy of IBUD in a sample of 24 non-treatment seeking individuals with either alcohol abuse or dependence treated with IBUD (50mg BID) and placebo. Participants will complete two separate 7-day inpatient stays at the UCLA CTRC during which they will take the study medication, complete an IV alcohol challenge, and take part in a stress-exposure and cue-exposure paradigms. Specific aims are to test whether IBUD (a) is safe in the context of alcohol administration, (b) attenuates alcohol-induced reinforcement, and (c) dampens stress-induced and cue-induced alcohol craving. In sum, this study will efficiently evaluate safety and initial efficacy of IBUD thereby screening novel medications for AD and elucidating potential mechanisms by which IBUD may be clinically efficacious. Results from this study will inform whether a randomized controlled trial of IBUD for alcoholism is warranted.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • age between 21 and 65
  • meet DSM-IV diagnostic criteria for alcohol abuse or dependence
  • report drinking at least 48 standard drinks in a 30-day period, during the 90 days before enrollment

Exclusion Criteria:

  • current treatment for alcohol problems, a history of treatment in the 30 days before enrollment or current treatment seeking;
  • current (last 12 months) DSM-IV diagnosis of dependence on any psychoactive substances other than alcohol and nicotine;
  • 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);
  • 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;
  • attempted suicide in the past 3 years and/or serious suicidal intention or plan in the past year;
  • currently on prescription medication that contraindicates use of IBUD;
  • any other circumstances that, in the opinion of the investigators, compromises participant safety

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ibudilast
Ibudilast will be administered for 7 days at the target dose of 50 mg/bid
Drug: Ibudilast
Ibudilast is a glial cell modulator that inhibits phosphodiesterases -4 and -10 and macrophage migration inhibitory factor.
Other Names:
  • MN-166, AV411
Placebo Comparator: Sugar pill
Placebo pills will be administered for 7 days and taken twice daily
Other: Matched placebo
A matched placebo (suggar pill) will be administered as a control condition.
Other Names:
  • Suggar pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Subjective response to alcohol
Time Frame: During the alcohol administration and observation period which is expected to last a total of 4 hours
Biphasic Alcohol Effects Scale (BAES) Alcohol Urge Questionnaire (AUQ)
During the alcohol administration and observation period which is expected to last a total of 4 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Stress-Induced Craving
Time Frame: During the stress exposure and observation period which is expected to last a total of 2 hours
Alcohol Urge Questionnaire (AUQ) & Differential Emotion Scale (DES)
During the stress exposure and observation period which is expected to last a total of 2 hours
Cue-Induced Alcohol Craving
Time Frame: During the cue-exposure and observation period which is expected to last a total of 2 hours
Alcohol Urge Questionnaire (AUQ)
During the cue-exposure and observation period which is expected to last a total of 2 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, Los Angeles

Collaborators

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2013

Primary Completion (Actual)

June 1, 2015

Study Completion (Actual)

June 1, 2015

Study Registration Dates

First Submitted

December 19, 2013

First Submitted That Met QC Criteria

December 30, 2013

First Posted (Estimate)

January 1, 2014

Study Record Updates

Last Update Posted (Estimate)

February 23, 2016

Last Update Submitted That Met QC Criteria

February 19, 2016

Last Verified

February 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IBUD
  • R21AA022214 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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