Ibudilast for Alcohol Use Disorder

(Ibudilast Trial)

Overseen By Rachel Weyl

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Pennsylvania

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

Disqualifiers: Serious psychiatric illness, Drug dependence, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the experimental drug Ibudilast can help people reduce or stop drinking alcohol. Used in Japan for its anti-inflammatory effects, Ibudilast might aid alcohol use reduction by decreasing inflammation. Participants will receive either Ibudilast or a placebo (a non-active substance) along with counseling over six weeks. The trial seeks physically healthy individuals who consume more than 24 (men) or 18 (women) standard drinks a week and wish to cut down or quit drinking. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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.

Is there any evidence suggesting that Ibudilast is likely to be safe for humans?

Research has shown that Ibudilast has been safely used for over 20 years in Asia for various health issues. Studies have found it well-tolerated for conditions like asthma and dizziness after a stroke. In one study, healthy volunteers took 60 mg of Ibudilast per day without problems. The drug appears to work similarly in both men and women.

Although the FDA has not yet approved Ibudilast for use in the United States, clinical trials have demonstrated its safety. Reports indicate that any side effects are usually mild and not serious. Overall, it has a good safety record, making it a potential option for those looking to reduce or stop alcohol use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for alcohol use disorder?

Ibudilast is unique because it offers a new approach to treating Alcohol Use Disorder by potentially targeting inflammation and neuroimmune pathways in the brain, unlike most current treatments that focus on altering neurotransmitter levels or blocking alcohol's effects. This drug is already known for treating other conditions like multiple sclerosis, which gives researchers hope that it can bring a fresh perspective to managing alcohol dependency. The excitement also stems from its potential dual action of reducing alcohol cravings and addressing underlying brain inflammation, which could make it a game-changer for those struggling with alcohol addiction.

What evidence suggests that Ibudilast might be an effective treatment for alcohol use disorder?

In this trial, participants will receive either ibudilast or a placebo. Research shows that ibudilast, a drug used in Japan for its anti-inflammatory effects, is under study as a potential treatment for alcohol use disorder. However, studies have found that taking 50 mg of ibudilast twice a day did not significantly reduce heavy drinking days compared to a placebo. While ibudilast may help with inflammation, its ability to reduce alcohol consumption remains unclear. Some research suggests it might benefit certain individuals, particularly those with pain, as ibudilast appears to weaken the connection between pain and heavy drinking. Overall, current evidence does not strongly support ibudilast as an effective treatment for reducing alcohol use in the general population. ^{6 7 8 9 10}

Who Is on the Research Team?

Henry Kranzler, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• Ibudilast

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.

How Is the Trial Designed?

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, United States for the following indications:

Approved in Japan as Ibudilast for:

• Bronchial asthma
• Cerebral vasospasm following subarachnoid hemorrhage

Approved in United States as MN-166 for:

• Multiple sclerosis
• Amyotrophic lateral sclerosis (ALS)
• Progressive multiple sclerosis
• Neuropathic pain

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

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]

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]

Ibudilast (IBUD) was found to be well tolerated in a study of 24 individuals with alcohol use disorder, but it did not significantly affect the primary measures of subjective response to alcohol.

However, IBUD showed promise in improving mood and reducing craving levels, particularly in individuals with higher depressive symptoms, suggesting it may help mitigate some effects of alcohol and could be a potential treatment for alcohol use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of the Neuroimmune Modulator Ibudilast for the Treatment of Alcoholism: A Randomized, Placebo-Controlled, Human Laboratory Trial. Ray, LA., Bujarski, S., Shoptaw, S., et al.[2022]

Pharmacological treatments for alcohol use disorders (AUD), such as acamprosate, naltrexone, nalmefene, and disulfiram, are effective but underused, highlighting the need for better implementation despite their proven efficacy.

Each medication has a distinct safety profile that must be carefully considered alongside individual patient circumstances, including their drinking patterns and any comorbid conditions, to optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Pharmacological Treatment of Alcohol Dependence: Comprehensive Review of Evidence. Sinclair, JM., Chambers, SE., Shiles, CJ., et al.[2018]

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]

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]

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]

Acamprosate and naltrexone are the only two medications approved for treating alcohol use disorders (AUDs) that have strong evidence from numerous clinical trials, making them effective options for patients.

Several off-label medications, such as topiramate and gabapentin, show promise for treating AUDs, but more research is needed to confirm their efficacy and safety in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy of alcoholism - an update on approved and off-label medications. Soyka, M., Müller, CA.[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]

Alcohol use disorder (AUD) is common but often under-treated, with only three approved medications, highlighting the need for more diverse and effective treatment options.

The review discusses various pharmacotherapies, including both approved and novel agents, showing promise for improving treatment efficacy and supporting personalized medicine approaches for individuals with AUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Agents for the Pharmacological Treatment of Alcohol Use Disorder. Burnette, EM., Nieto, SJ., Grodin, EN., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05414240

NCT05414240 | Ibudilast for Treating Alcohol Use Disorder By reducing inflammation, Ibudilast may help some people reduce or stop drinking. We have obtained an Investigational New Drug Application (IND) approval for ...

2. investors.medicinova.com investors.medicinova.com/news-releases/news-release-details/medicinova-announces-presentation-results-phase-2b-trial-mn-166

MediciNova Announces Presentation of Results from the ... MN-166 (ibudilast) treatment was not superior to placebo for reducing percent heavy drinking days. Also, MN-166 (ibudilast) treatment was not superior to ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0741832925001235

Ibudilast Attenuates the Association Between Pain Intensity ... Ibudilast attenuated the positive association between baseline pain intensity and heavy drinking, suggesting that pain intensity may identify an ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40305022/

A Neuroimmune Modulator for Alcohol Use Disorder - PubMed Registered exploratory analyses also tested whether ibudilast reduced inflammation compared with placebo, as indicated by circulating levels of ...

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2833329

A Neuroimmune Modulator for Alcohol Use Disorder A twice-daily 50 mg dose of ibudilast did not significantly reduce the percentage of heavy drinking days compared with placebo.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7488583/

Ibudilast for alcohol use disorder: study protocol for a ... This study will further develop ibudilast, a safe and promising novel compound with strong preclinical and clinical safety data for AUD, and will probe ...

7. investors.medicinova.com investors.medicinova.com/news-releases/news-release-details/medicinova-announces-completion-enrollment-phase-2b-clinical

MediciNova Announces Completion of Enrollment in the ... The clinical trial evaluated MN-166 (ibudilast) as a potential treatment to decrease alcohol consumption in treatment-seeking individuals ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03533387?term=IBUDILAST&rank=4

Study of MN-166 (Ibudilast) Extended Release Tablet ... Compare the number and frequency of treatment-emergent adverse events (serious and non-serious) profiles of two different formulations MN-166 50mg, extended ...

9. investors.medicinova.com investors.medicinova.com/news-releases/news-release-details/medicinova-announces-new-data-and-results-mn-166-ibudilast

MediciNova Announces New Data and Results of MN-166 ... The primary objective of this nonclinical efficacy study was to determine the safety and pharmacological activity of MN-166 (ibudilast) ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2675769/

Ibudilast in healthy volunteers: safety, tolerability and ... Overall, ibudilast administered at 60 mg day−1 was well tolerated. The PK data showed no apparent difference between men and women in ibudulast PK profiles.