Ibudilast for Alcohol Use Disorder

(Ibudilast Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Henry Kranzler, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Pennsylvania

Must not be taking: Psychotropics, Benzodiazepines, Anticonvulsants, others

Disqualifiers: Serious psychiatric illness, Drug dependence, others

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This is a research study involving 6 weeks of study medication, Ibudilast or a placebo (an inactive substance) and medical management counseling to reduce or stop drinking. Ibudilast is not approved by the U.S. FDA for clinical use in the United States, but it is has been used for many years in Japan for its anti-inflammatory effects. Its use in the treatment of alcohol dependence is experimental. By reducing inflammation, Ibudilast may help some people reduce or stop drinking. We have obtained an Investigational New Drug Application (IND) approval for this study from the FDA. Ibudilast has been used clinically for 20 years in Asia for treating bronchial asthma and, more recently, for post-stroke dizziness and ocular allergies and has been shown to be safe and well tolerated.

Will I have to stop taking my current medications?

If you are currently taking psychotropic medications (drugs that affect the mind) or medications to treat alcohol dependence, you will need to stop them to participate in this trial. However, if you are on a stable antidepressant treatment for at least one month, you can continue taking it.

What data supports the effectiveness of the drug Ibudilast for treating alcohol use disorder?

Research shows that Ibudilast may help reduce alcohol cravings and improve mood in people with alcohol use disorder, especially those with higher levels of depression. It also appears to have anti-inflammatory effects, which might contribute to its potential benefits in reducing alcohol consumption. ^{1 2 3 4 5}

Is Ibudilast safe for human use?

The provided research articles do not contain specific safety data for Ibudilast (also known as MN-166, AV-411, or Ketas) in humans. ^{5 6 7 8 9}

How is the drug Ibudilast unique in treating alcohol use disorder?

Ibudilast is unique because it is a neuroimmune modulator that targets inflammation pathways in the brain, which is different from most other treatments for alcohol use disorder. It works by reducing inflammation and altering mood and craving, potentially making it effective for people with depressive symptoms. ^{1 2 3 4 10}

Research Team

Henry Kranzler, MD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

This trial is for adults who drink heavily (over 24 drinks weekly for men, over 18 for women) and want to reduce or stop drinking. They must be physically healthy, not pregnant, able to understand English well, and have no serious mental illness or drug dependence other than alcohol, marijuana or nicotine.

Inclusion Criteria

Willingness to provide signed, informed consent and commit to completing the procedures in the study

I drink more than the recommended amount of alcohol weekly.

I am not breastfeeding, using birth control, and have a negative pregnancy test.

Exclusion Criteria

I do not have any significant current illnesses or abnormal lab results.

I am currently taking medication for mental health or alcohol dependence.

You have a severe mental illness at the moment.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person or virtual)

Treatment

Participants receive Ibudilast or placebo for 6 weeks with medical management counseling

6 weeks

1 visit (in-person) at week 1, biweekly visits (in-person) at weeks 2, 3, and 4, and an endpoint visit at week 6

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Ibudilast (Anti-inflammatory agent)

Trial Overview The study tests Ibudilast's ability to help people cut down or quit drinking by reducing inflammation. Participants will receive either Ibudilast or a placebo alongside counseling for six weeks. The effectiveness of Ibudilast in treating alcohol use disorder is experimental.

Participant Groups

Group I: Ibudilast Active Control 2 Interventions

IBUD at a dosage of 20 mg twice daily for 2 days, with an increase to 50 mg twice daily on day 3. The dosage will remain at 50 mg twice daily through most of the rest of the 6-week treatment period. However, for the last three days of week 6, participants will reduce the dosage gradually to 20 mg twice daily prior to discontinuing it at the end of the treatment period.

Group II: Inactive placebo Placebo Group 2 Interventions

Placebo twice daily for 6-week treatment period. Placebo will match active medication in appearance and size.

Ibudilast is already approved in Japan for the following indications:

Approved in Japan as Ibudilast for:

• Bronchial asthma
• Cerebral vasospasm following subarachnoid hemorrhage

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Dr. Joan Lau

University of Pennsylvania

Chief Executive Officer since 2020

PhD in Neuroscience from the University of Cincinnati College of Medicine, MBA from the Wharton School of Business, BS in Bioengineering from the University of Pennsylvania

Dr. Robert Iannone

University of Pennsylvania

Chief Medical Officer since 2019

MD from Yale University, MSCE from the University of Pennsylvania

Findings from Research

Ibudilast (IBUD) was found to effectively reduce alcohol craving in individuals with alcohol use disorder, but it did not suppress cravings for high-fat/high-sugar foods, indicating that it may not affect all appetitive behaviors.

The study revealed that while IBUD did not change food cravings after alcohol infusion, it actually increased cravings for high-fat/high-sugar foods following psychological stress, particularly in individuals with lower depressive symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does the Neuroimmune Modulator Ibudilast Alter Food Craving? Results in a Sample With Alcohol Use Disorder. Cummings, JR., Tomiyama, AJ., Ray, LA.[2022]

A 12-week clinical trial involving 132 participants will evaluate the efficacy of ibudilast, a phosphodiesterase inhibitor, in treating alcohol use disorder (AUD), focusing on outcomes like percent heavy drinking days and alcohol craving.

Ibudilast has shown promising safety data and targets neurotrophin signaling and neuroimmune function, potentially offering a novel approach to AUD treatment if it proves more effective than placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibudilast for alcohol use disorder: study protocol for a phase II randomized clinical trial. Burnette, EM., Baskerville, WA., Grodin, EN., et al.[2021]

In a preliminary study involving 52 individuals with alcohol use disorder, ibudilast treatment for 2 weeks resulted in lower levels of certain inflammatory markers, suggesting it may have anti-inflammatory effects in humans.

The study found that changes in specific neurometabolite markers, particularly lower choline levels in the brain, were associated with reduced drinking behavior, indicating a potential mechanism through which ibudilast may help treat alcohol use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of ibudilast on central and peripheral markers of inflammation in alcohol use disorder: A randomized clinical trial. Grodin, EN., Nieto, SJ., Meredith, LR., et al.[2023]

In a 23-day study involving 23 non-treatment-seeking, alcohol-dependent individuals, both naltrexone and acamprosate were found to be behaviorally and pharmacologically safe, with only moderate and infrequent adverse events reported.

The combination of naltrexone and acamprosate resulted in more side effects compared to either medication alone, but overall, the increased symptoms did not lead to significant clinical deterioration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-ranging kinetics and behavioral pharmacology of naltrexone and acamprosate, both alone and combined, in alcohol-dependent subjects. Johnson, BA., O'Malley, SS., Ciraulo, DA., et al.[2018]

Current medications for alcohol use disorder (AUD), including disulfiram, naltrexone, acamprosate, and the newly approved nalmefene, have limited efficacy, benefiting only a small number of individuals with AUD.

Research is ongoing to develop new medications targeting various pharmacological pathways, with a focus on improving effectiveness and safety, which is crucial for better treatment outcomes for patients with AUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in Pharmacotherapy Development: Human Clinical Studies. Litten, RZ., Falk, DE., Ryan, ML., et al.[2022]

Ibudilast, a non-selective phosphodiesterase inhibitor, significantly reduced alcohol consumption by about 50% in alcohol-preferring rats and was effective in alcohol-dependent mice without affecting non-dependent mice.

These results suggest that ibudilast could be a promising pharmacotherapy for alcohol dependence, targeting neuroinflammatory pathways in the central nervous system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibudilast reduces alcohol drinking in multiple animal models of alcohol dependence. Bell, RL., Lopez, MF., Cui, C., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Development of the Neuroimmune Modulator Ibudilast for the Treatment of Alcoholism: A Randomized, Placebo-Controlled, Human Laboratory Trial. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Does the Neuroimmune Modulator Ibudilast Alter Food Craving? Results in a Sample With Alcohol Use Disorder. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Ibudilast for alcohol use disorder: study protocol for a phase II randomized clinical trial. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Effects of ibudilast on central and peripheral markers of inflammation in alcohol use disorder: A randomized clinical trial. [2023]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Novel Agents for the Pharmacological Treatment of Alcohol Use Disorder. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Pharmacological Treatment of Alcohol Dependence: Comprehensive Review of Evidence. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Pharmacotherapy of alcoholism - an update on approved and off-label medications. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Dose-ranging kinetics and behavioral pharmacology of naltrexone and acamprosate, both alone and combined, in alcohol-dependent subjects. [2018]

9. Germany pubmed.ncbi.nlm.nih.gov

Advances in Pharmacotherapy Development: Human Clinical Studies. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Ibudilast reduces alcohol drinking in multiple animal models of alcohol dependence. [2023]