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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Methamphetamine-dependence
• Intervention / Treatment: Drug: Placebo Oral Tablet; Drug: Ibudilast

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Laura Dennis, BS; Phone Number: 56707 (503) 220-8262; Email: laura.dennis@va.gov
• Study Contact Backup: Name: Milky Kohno, PhD; Phone Number: (503) 721-7964; Email: kohno@ohsu.edu

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97207-2964
      • Recruiting
      • VA Portland Health Care System, Portland, OR
      • Contact: Milky Kohno, PhD; Phone Number: 503-721-7964; Email: kohno@ohsu.edu
      • Principal Investigator: Milky Kohno, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 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; Placebo capsules will be orally ingested twice daily for 6 weeks.
Active Comparator: Ibudilast; 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; Ibudilast capsules will be orally ingested twice daily for 6 weeks.
No Intervention: Controls; Healthy controls will only undergo baseline evaluations and will not be enrolled in the drug portion of the study.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: Oregon Health and Science University; Portland VA Medical Center
• Investigators: Principal Investigator: Milky Kohno, PhD, VA Portland Health Care System, Portland, OR

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: October 26, 2017
• First Submitted That Met QC Criteria: November 8, 2017
• First Posted (Actual): November 14, 2017

Study Record Updates

• Last Update Posted (Estimated): January 8, 2024
• Last Update Submitted That Met QC Criteria: January 5, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Neuroinflammation; Methamphetamine; Ibudilast
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Inflammation; Neuroinflammatory Diseases; 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: NURA-001-17F; 16768 (Other Identifier: Portland VA Medical Center); 18176 (Other Grant/Funding Number: OHSU); 20053 (Other Grant/Funding Number: OHSU Circle of Giving)

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
• product manufactured in and exported from the U.S.: No