Ibudilast for the Treatment of Alcohol Use Disorder

A Randomized Controlled Clinical Trial of the Neuroimmune Modulator Ibudilast for the Treatment of Alcohol Use Disorder

This study is a double-blind, placebo-controlled randomized clinical trial of IBUD (50mg BID) for the treatment of Alcohol Use Disorder (AUD). Eligible participants will undergo a 12-week medication treatment period and 5 in-person visits over 16 weeks.

Study Overview

• Status: Completed
• Conditions: Alcohol Use Disorder
• Intervention / Treatment: Drug: Ibudilast; Drug: Placebo oral capsule

Detailed Description

The study design consists of a 12-week, double-blind, placebo-controlled randomized clinical trial of IBUD (50mg BID) for the treatment of Alcohol Use Disorder (AUD). The investigators will randomize 132 treatment-seekers with current AUD over the course of 4 years. As a behavioral support platform, all participants will complete the NIAAA-developed and computer-delivered program "Take Control" during the study. Participants will complete telephone screening, followed by in-person eligibility assessment, a physical exam for medical eligibility, randomization to study medication or matched placebo, and in-person follow-up visits at 4, 8, and 12 weeks of treatment. TLFB assessment of drinking outcomes will also occur by telephone on weeks 2, 6, and 10. A final safety check visit will occur on week 16, consisting of repeated clinical labs and ECG.

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Be between the ages of 18 and 65
2. Meet current (i.e., past 12 months) DSM-5 diagnostic criteria for alcohol use disorder moderate or severe
3. Be treatment-seeking for AUD
4. Report drinking at least 28 drinks per week if male (21 drinks per week if female) in the 28 days prior to consent

Exclusion Criteria:

1. Have a current (last 12 months) DSM-5 diagnosis of substance use disorder for any psychoactive substances other than alcohol and nicotine
2. Have a lifetime DSM-5 diagnosis of schizophrenia, bipolar disorder, or any psychotic disorder
3. Have a positive urine screen for narcotics, amphetamines, or sedative hypnotics;
4. Have clinically significant alcohol withdrawal symptoms as indicated by a score ≥ 10 on the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-R)

5. Be pregnant, nursing, or planning to become pregnant while taking part in the study; and must agree to one of the following methods of birth control (if female), unless she or partner are surgically sterile:

   • Oral contraceptives
   • Contraceptive sponge
   • Patch
   • Double barrier
   • Intrauterine contraceptive device
   • Etonogestrel implant
   • Medroxyprogesterone acetate contraceptive injection
   • Complete abstinence from sexual intercourse
   • Hormonal vaginal contraceptive ring
6. Have a medical condition that may interfere with safe study participation (e.g., unstable cardiac, renal, or liver disease, uncontrolled hypertension or diabetes)
7. Have AST, ALT, or GGT ≥ 3 times upper normal limit
8. Have attempted suicide in the past 3 years and/or have had serious suicidal intention or plan in the past year
9. Currently be on prescription medication that contraindicates use of IBUD, including alpha or beta agonists, theophylline, or other sympathomimetic
10. Currently be on any medications for AUD or any psychotropic medications (e.g., psychostimulants and benzodiazepines) with the exception of stable antidepressants (stable dose for ≥4 weeks)
11. Have any other circumstances that, in the opinion of the investigators, compromises participant safety.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ibudilast; 10mg delayed-release capsules, target dose 50mg BID (5 x 10mg capsules twice daily) for 12 weeks	Drug: Ibudilast; targets neurotrophin signaling and neuroimmune function; Other Names: MN-166; Pinatos
Placebo Comparator: Placebo Oral Capsule; matched to experimental drug	Drug: Placebo oral capsule; matched to active drug, ibudilast; Other Names: Sugar Pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent heavy drinking days	Heavy drinking days defined as 5+ drinks for men and 4+ for women	12 week-treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drinks per day	secondary alcohol consumption endpoint	12-week treatment period
Drinks per drinking day	secondary alcohol consumption endpoint	12-week treatment period
Percent days abstinent	secondary alcohol consumption endpoint	12-week treatment period
Percent subjects with no heavy drinking days	secondary alcohol consumption endpoint	12-week treatment period
Percent subjects abstinent	secondary alcohol consumption endpoint	12-week treatment period

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depressive Symptomatology	Responses from Beck Depression Inventory II (BDI-II) will be used to test this outcome	12-week treatment period
Neuroinflammation	Blood levels of proinflammatory markers	12-week treatment period

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA); MediciNova
• Investigators: Principal Investigator: Lara A. Ray, PhD, University of California, Los Angeles

Publications and helpful links

General Publications

• Burnette EM, Baskerville WA, Grodin EN, Ray LA. Ibudilast for alcohol use disorder: study protocol for a phase II randomized clinical trial. Trials. 2020 Sep 11;21(1):779. doi: 10.1186/s13063-020-04670-y.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Actual): April 19, 2023
• Study Completion (Actual): April 19, 2023

Study Registration Dates

• First Submitted: July 11, 2018
• First Submitted That Met QC Criteria: July 11, 2018
• First Posted (Actual): July 20, 2018

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: ibudilast, treatment, medication development
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Alcohol Drinking; Alcoholism; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Phosphodiesterase Inhibitors; Ibudilast
• Other Study ID Numbers: 18-000963; R01AA026190 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No