Ibudilast for Methamphetamine Addiction

(Ibudilast Trial)

Overseen By Milky Kohno, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

Must not be taking: Psychotropic medications

Disqualifiers: Neurological, Endocrine, Psychiatric, 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: Unknown

Duration: 6 weeks

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called ibudilast to determine if it can help people stop using methamphetamine, which currently has no treatments for addiction. Methamphetamine addiction poses a significant problem in the U.S., and new solutions are needed. Participants will receive either ibudilast or a placebo (a pill with no active drug) for six weeks. This trial suits individuals with methamphetamine addiction who only use methamphetamine and marijuana, with negative drug tests on test days. 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 advancements in addiction treatment.

Will I have to stop taking my current medications?

The trial requires that participants do not use any recreational or prescriptive psychotropic medications (drugs that affect the mind) during the study.

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

Research has shown that ibudilast has been tested for safety in people. In earlier studies, more than 450 participants took ibudilast, and it was generally well-tolerated, with no serious side effects linked to its use. Another study tested ibudilast with methamphetamine and found no additional heart problems or serious issues when both drugs were used together. Overall, the evidence suggests that ibudilast is safe for people, even those using methamphetamine. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for methamphetamine addiction?

Researchers are excited about ibudilast for methamphetamine addiction because it offers a new approach by targeting neuroinflammation, which isn't directly addressed by current treatments. Unlike other options that focus on replacing the drug or managing withdrawal symptoms, ibudilast works by reducing inflammation in the brain, potentially decreasing cravings and improving cognitive function. This novel mechanism of action could provide a more comprehensive solution for individuals struggling with methamphetamine addiction.

What evidence suggests that ibudilast might be an effective treatment for methamphetamine addiction?

Research has shown that ibudilast, which participants in this trial may receive, might help reduce methamphetamine addiction by addressing brain inflammation. Studies have found that ibudilast can lessen the effects of methamphetamine, potentially helping people use the drug less. In one study, participants taking ibudilast reported feeling fewer effects from methamphetamine, which could make quitting easier. Researchers are also examining the safety of ibudilast as a treatment for methamphetamine dependence, a promising sign. While more research is needed, these early findings suggest that ibudilast could be a useful option for treating methamphetamine addiction. ^{1 3 6 7 8}

Who Is on the Research Team?

Milky Kohno, PhD

Principal Investigator

VA Portland Health Care System, Portland, OR

Are You a Good Fit for This Trial?

This trial is for individuals who are currently using methamphetamine but not other drugs, except marijuana. They must have a recent diagnosis of Methamphetamine-Use Disorder and cannot be pregnant or breastfeeding, nor can they have neurodegenerative diseases, severe liver disease, certain psychiatric disorders, or be on psychotropic medications.

Inclusion Criteria

Meet diagnosis for recent Methamphetamine-Use Disorder (DSM-V) or does not meet any substance-use disorders

I only use marijuana or methamphetamine and will test negative for other drugs.

Exclusion Criteria

My genetic test shows low TSPO binding, reducing radiation risk.

I do not have major health issues that could affect my safety or the study results.

I have a brain disorder that causes brain swelling.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ibudilast or placebo for 6 weeks with pre/post evaluations for neuroinflammation and associated behaviors

6 weeks

Pre and post evaluations

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ibudilast

Trial Overview The study is testing Ibudilast—a potential medication to help with methamphetamine addiction—against a placebo (a pill without active drug). Participants will receive either the study drug or placebo to assess if Ibudilast reduces neuroinflammation associated with meth use.

How Is the Trial Designed?

Group I: Controls Active Control 1 Intervention

Healthy controls will only undergo baseline evaluations and will not be enrolled in the drug portion of the study.

Group II: Ibudilast Active Control 1 Intervention

Ibudilast Group will be dosed with ibudilast twice daily for 6 weeks. The first 2 weeks will be 20 mg twice daily followed by 4 weeks of 50 mg twice daily. Participants will have pre/post evaluations for neuroinflammation and associated behaviors

Group III: Placebo Placebo Group 1 Intervention

Placebo Group will be dosed with a placebo oral tablet twice daily for 6 weeks. Participants will have pre/post evaluations for neuroinflammation and associated behaviors

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?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Portland VA Medical Center

Collaborator

Trials

44

Recruited

7,800+

Published Research Related to This Trial

In a randomized, placebo-controlled trial involving 125 participants with methamphetamine use disorder, ibudilast (50 mg twice daily) did not significantly improve rates of methamphetamine abstinence compared to placebo, with both groups showing similar abstinence rates (14% for ibudilast vs. 16% for placebo).

Ibudilast was well tolerated by participants, but the study did not find a correlation between serum ibudilast levels and methamphetamine use, suggesting that targeting neuroinflammation with this medication may not be an effective treatment strategy for methamphetamine use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, Placebo-Controlled Trial of Targeting Neuroinflammation with Ibudilast to Treat Methamphetamine Use Disorder. Heinzerling, KG., Briones, M., Thames, AD., et al.[2021]

In a study involving 11 adult volunteers with methamphetamine dependence, ibudilast significantly reduced several subjective effects of methamphetamine, such as feelings of being 'High' and 'Good', particularly at the higher dose of 100 mg.

The results suggest that ibudilast may work by targeting neuroinflammation, a novel approach in treating methamphetamine dependence, indicating its potential for further clinical evaluation as a therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibudilast attenuates subjective effects of methamphetamine in a placebo-controlled inpatient study. Worley, MJ., Swanson, A-N., Heinzerling, KG., et al.[2023]

Ibudilast significantly increased cell viability and reduced cell death in methamphetamine-treated PC12 cells, demonstrating its potential as a neuroprotective agent against methamphetamine-induced toxicity.

The study found that ibudilast inhibited σ receptor activation, leading to decreased calcium levels, reduced oxidative stress, and lower caspase 3 activity, suggesting a mechanism of action that involves modulation of cAMP production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Signal Transduction of Improving Effects of Ibudilast on Methamphetamine Induced Cell Death. Tahvilian, R., Amini, K., Zhaleh, H.[2020]

Ibudilast, AV1013, and minocycline significantly reduced methamphetamine self-administration in rats, indicating that targeting glial cell activation may be an effective strategy for treating methamphetamine abuse.

The study involved Long-Evans hooded rats trained to self-administer methamphetamine, with the treatments administered over three days, showing that glial cell inhibitors can attenuate drug-seeking behavior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glial cell modulators attenuate methamphetamine self-administration in the rat. Snider, SE., Hendrick, ES., Beardsley, PM.[2021]

In a randomized, double-blind, placebo-controlled trial involving intravenous methamphetamine administration, ibudilast was found to be well tolerated, showing similar rates of adverse events compared to placebo.

Ibudilast did not significantly affect the cardiovascular response or the pharmacokinetics of methamphetamine, suggesting it may be a safe option for further studies on treating methamphetamine dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Intravenous Methamphetamine Administration During Ibudilast Treatment. DeYoung, DZ., Heinzerling, KG., Swanson, AN., et al.[2019]

In a study involving 11 participants with methamphetamine dependence, ibudilast (50mg twice daily) significantly improved attention by reducing variability in response times and decreasing perseverative responses compared to a placebo.

These results suggest that ibudilast may help protect sustained attention during early abstinence from methamphetamine, indicating its potential as a treatment option for improving attentional deficits associated with substance dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibudilast may improve attention during early abstinence from methamphetamine. Birath, JB., Briones, M., Amaya, S., et al.[2018]

In a clinical trial with 11 patients, treatment with Ibudilast (IBUD) significantly reduced inflammatory markers (sICAM-1, sVCAM-1, and cathepsin D) that increased after a methamphetamine (METH) challenge, suggesting its potential to mitigate inflammation associated with METH use.

The study indicates that IBUD may be beneficial in treating methamphetamine use disorder by attenuating the acute pro-inflammatory effects of METH, which could improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibudilast attenuates peripheral inflammatory effects of methamphetamine in patients with methamphetamine use disorder. Li, MJ., Briones, MS., Heinzerling, KG., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/ct2/show/results/NCT01860807?term=ibudilast

Trial of Ibudilast for Methamphetamine Dependence These trials gather additional information about a drug's safety, efficacy, or optimal use. Phase Not Applicable. Describes trials without FDA-defined phases ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31820289/

Randomized, Placebo-Controlled Trial of Targeting ... - PubMed Methamphetamine (MA) triggers neuroinflammation and medications that counteract MA-induced neuroinflammation may reduce MA-induced neurodegeneration and improve ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01217970

Safety Interaction Trial Ibudilast and Methamphetamine This study is designed to collect data to determine whether a medication, ibudilast, is safe for use as a potential treatment for methamphetamine-dependent ...

4. medicinova.com medicinova.com/clinical-development/core/mn-166/methamphetamine-addiction/

Methamphetamine Addiction Additional endpoints include the effect of ibudilast on methamphetamine use and neurocognitive performance as well as regulation of HIV-associated factors such ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5349508/

Ibudilast attenuates subjective effects of methamphetamine in ... The mean past-month drug use was 17.4 days (SD = 9.6) for methamphetamine, 10.2 (SD = 8.8) for alcohol, and 5.2 days (SD = 7.4) for marijuana. The ibudilast ...

6. reporter.nih.gov reporter.nih.gov/project-details/8284393

Phase I Safety Interaction Trial of Ibudilast ... - NIH RePORTER Results of this study will provide the safety-interaction data required before a Phase II clinical trial to assess the efficacy of ibudilast for treatment of MA ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27269956/

Safety of Intravenous Methamphetamine Administration ... Conclusions: Methamphetamine administration during ibudilast treatment was well tolerated without additive cardiovascular effects or serious adverse events, ...

8. openaccessjournals.com openaccessjournals.com/articles/ibudilast-for-the-treatment-of-drug-addiction-and-other-neurological-conditions.pdf

Ibudilast for the treatment of drug addiction and other ... In the completed Phase I and II clinical studies described above, over 450 subjects have been treated with ibudilast and safety and tolerability outcomes to ...