Pilot Study of the Effect of Ibudilast on Neuroinflammation in Methamphetamine Users

Study Overview
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Brief Summary
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Addiction to methamphetamine is a serious health problem in the United States. Right now, there are no medications that a doctor can give someone to help them stop using methamphetamine. More research is needed to develop drugs for methamphetamine addiction. Ibudilast (the study drug) is a drug that could help people addicted to methamphetamine.

Detailed Description
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Addiction to methamphetamine is a serious health problem in the United States. Right now, there are no medications that a doctor can give someone to help them stop using methamphetamine. More research is needed to develop drugs for methamphetamine addiction. Ibudilast (the study drug) is a drug that could help people addicted to methamphetamine. The investigators are interested to know if the study drug can help some symptoms that methamphetamine can cause, specifically inflammation in the brain. Inflammation has been shown to affect decision-making. The study drug has anti-inflammatory properties, however it is not yet known whether the drug will reduce inflammation in the brain.

Official Title
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Brain Function and Connectivity in Methamphetamine Dependence: The Link to Neuroinflammation and the Effects of Ibudilast

Conditions
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Methamphetamine-dependence

Intervention / Treatment
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* Drug: Ibudilast
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: abstinent from all drugs except marijuana and methamphetamine and have a negative urine drug screen on test days Meet diagnosis for recent Methamphetamine-Use Disorder (DSM-V) or does not meet any substance-use disorders Exclusion Criteria: Known sensitivity to ibudilast Left handed MRI contraindications Clinically significant neurological, endocrine, renal, hepatic, or systemic diseases that would compromise safe participation or confound outcomes Any psychiatric diagnoses or primary psychotic or mood disorders (past depression diagnoses allowed) Any drug use disorder diagnosis besides methamphetamine or tobacco Any recreational or prescriptive use of psychotropic medications Claustrophobia Women who are pregnant or breast-feeding Neurodegenerative diseases that present with neuroinflammation More than 4 weeks abstinent from methamphetamine rs6971 genotype that confers low translocator protein (TSPO) binding affinity to prevent unnecessary radiation exposure Liver disease requiring medication or medical treatment and/or aspartate or alanine aminotransferase levels greater than 3 times the upper limit Participation in any drug study in the last 3 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Healthy controls will be recruited and have baseline evaluations for neuroinflammation and associated behaviors. Participants with methamphetamine-use disorder will also be recruited and enrolled in a placebo controlled portion of this study. Participants in the placebo controlled portion of this study will be dosed with either the study drug or a placebo twice daily for 6 weeks and will have pre/post evaluations for neuroinflammation and associated behaviors.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>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 | Drug: Placebo Oral Tablet<br>* Placebo capsules will be orally ingested twice daily for 6 weeks.<br>|
| Active Comparator: Ibudilast<br>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 | Drug: Ibudilast<br>* Ibudilast capsules will be orally ingested twice daily for 6 weeks.<br>|
| No Intervention: Controls<br>Healthy controls will only undergo baseline evaluations and will not be enrolled in the drug portion of the study. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of ibudilast on neuroinflammation as assessed by positron emission tomography (PET) | Pre and post differences in brain neuroinflammation will be assessed. | 6 weeks | 
| Effects of ibudilast on brain function as assessed by magnetic resonance imaging (MRI) | Pre and post differences in brain function will be assessed. | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of ibudilast on overall cognitive battery score. | Pre and post differences in overall cognitive battery score will be assessed. | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ibudilast, Methamphetamine, Neuroinflammation