Development of Ibudilast for Alcohol Use Disorder

Phase 1

Completed

• Conditions: Alcohol Use Disorders
• Interventions: Drug: Ibudilast; Other: Matched placebo

• Registration Number: NCT02025998
• Lead Sponsor: University of California, Los Angeles

Brief Summary

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.

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 Timeline

• Study Start: 2013-12
• Study First Submitted: 2013-12-19
• Study First Submitted QC: 2013-12-30
• Study First Posted: 2014-01-01
• Primary Completion: 2015-06
• Study Completion: 2015-06
• Status Verified: 2016-02
• Last Update Submitted: 2016-02-19
• Last Update Posted: 2016-02-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Ibudilast	Ibudilast	Ibudilast will be administered for 7 days at the target dose of 50 mg/bid
Sugar pill	Matched placebo	Placebo pills will be administered for 7 days and taken twice daily

Primary Outcome Measures

Name	Time	Method
Subjective response to alcohol	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)

Secondary Outcome Measures

Name	Time	Method
Cue-Induced Alcohol Craving	During the cue-exposure and observation period which is expected to last a total of 2 hours	Alcohol Urge Questionnaire (AUQ)
Stress-Induced Craving	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)

Trial Locations

Locations (1)

UCLA Addictions Laboratory; 🇺🇸 Los Angeles, California, United States