Development of Ibudilast for Alcohol Use Disorder

Alcohol Use Disorders Clinical Trial

Official title:

Development of Ibudilast as a Novel Treatment for Alcohol Dependence

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02025998
• Other study ID #: IBUD
• Secondary ID: R21AA022214
• Status: Completed
• Phase: Phase 1
• First received: December 19, 2013
• Last updated: February 19, 2016
• Start date: December 2013
• Est. completion date: June 2015

Study information

• Verified date: February 2016
• Source: University of California, Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 65 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alcohol Drinking
• Alcohol Use Disorders

Intervention

Drug:
• Ibudilast
Ibudilast is a glial cell modulator that inhibits phosphodiesterases -4 and -10 and macrophage migration inhibitory factor.

Other:
• Matched placebo
A matched placebo (suggar pill) will be administered as a control condition.

Locations

Country	Name	City	State
United States	UCLA Addictions Laboratory	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, Los Angeles	National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Subjective response to alcohol	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	No
Secondary	Stress-Induced Craving	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	No
Secondary	Cue-Induced Alcohol Craving	Alcohol Urge Questionnaire (AUQ)	During the cue-exposure and observation period which is expected to last a total of 2 hours	No

External Links

•   UCLA Addictions Laboratory