Safety Interaction Trial Ibudilast and Methamphetamine

Sponsor

University of California, Los Angeles (Other)

Overall Status

Completed

CT.gov ID

NCT01217970

Collaborator

National Institute on Drug Abuse (NIDA) (NIH), MediciNova (Industry)

Enrollment

Location

Arms

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is designed to collect data to determine whether a medication, ibudilast, is safe for use as a potential treatment for methamphetamine-dependent people. For 18 years in Japan and South Korea, ibudilast has been used safely in humans as a treatment for asthma, pulmonary, and cardiovascular disease. It is not known whether ibudilast is safe to use in outpatient settings with people who have methamphetamine dependence. This would be the first study to collect this information. This study is important because individuals with methamphetamine dependence often relapse to meth use, even when in treatment; some number of individuals who participate in an outpatient study will relapse to methamphetamine while taking ibudilast. It is crucial to know whether there may be interactions between ibudilast and methamphetamine before planning an outpatient clinical trial.Ibudilast is an exciting medication candidate for treating methamphetamine dependence. When individuals become abstinent from methamphetamine during early recovery, the body starts an inflammatory process in neurons, especially glial cells. Glial cells are important in that they provide support to the nerve cells that are involved in thought, movement, and other human activities. By dampening inflammation in glial cells, ibudilast may preserve glial and other nerve cells during early abstinence, which in turn may help individuals feel better and think better during treatment.

The study specific aims are to determine whether ibudilast alters:

blood pressure and heart rate responses to methamphetamine;
the ratings of craving or other drug experiences from methamphetamine;
the reward/reinforcing effects of methamphetamine; and
the metabolism of methamphetamine.

Over an enrollment period of 24 months, 12 methamphetamine-dependent participants who are not looking for treatment will complete this study.

Condition or Disease	Intervention/Treatment	Phase
Methamphetamine-dependence Substance Abuse	Drug: Ibudilast Drug: Ibudilast Drug: Ibudilast	Phase 1

Detailed Description

The study will be conducted at the Harbor-UCLA hospital to ensure the medical safety of participants, especially if there are unexpected interactions between ibudilast and methamphetamine on cardiovascular function. Methamphetamine can cause substantial increases in heart rate and blood pressure that last for about 3 hours. This study will measure whether people who are meth-dependent (and not looking for treatment) show increases in their heart rate and blood pressures when given methamphetamine above what is expected by methamphetamine alone and when at the recommended doses of ibudilast.

Ibudilast is an exciting medication candidate for treating methamphetamine dependence. When individuals become abstinent from methamphetamine during early recovery, the body starts an inflammatory process in neurons, especially glial cells. Glial cells are important in that they provide support to the nerve cells that are involved in thought, movement, and other human activities. By dampening inflammation in glial cells, ibudilast may preserve glial and other nerve cells during early abstinence, which in turn may help individuals feel better and think better during treatment.

The study specific aims are to determine whether ibudilast alters:

blood pressure and heart rate responses to methamphetamine;
the ratings of craving or other drug experiences from methamphetamine;
the reward/reinforcing effects of methamphetamine; and
the metabolism of methamphetamine.

Over an enrollment period of 24 months, 12 methamphetamine-dependent participants who are not looking for treatment will complete this study. Each participant will complete assessments of safety/tolerability, perceived effects of methamphetamine, and an assessment where subjects make choices between different amounts of money and methamphetamine. Each patient will stay in the hospital for a total of 27 nights. The first two days consist of safety infusions to make sure methamphetamine is tolerable. Then, each subject will start study medication and take a 7-day course of three conditions: placebo, ibudilast 20mg BID, and ibudilast 50mg ibudilast. Low dose ibudilast always precedes high dose ibudilast. The order of placebo being first or last is random.

Study Design

Study Type:

Interventional

Actual Enrollment :

11 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Official Title:

Phase I Safety Interaction Trial of Ibudilast With Methamphetamine

Study Start Date :

Jan 1, 2011

Actual Primary Completion Date :

Mar 1, 2013

Actual Study Completion Date :

Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Ibudilast 20mg BID Ibudilast 20mg oral BID 7 days	Drug: Ibudilast Ibudilast oral 20mg BID for 7 days Other Names: MN166, AV411
Active Comparator: Ibudilast 50mg BID Ibudilast 50mg oral BID 7 days	Drug: Ibudilast Ibudilast oral 50mg BID for 7 days Other Names: MN166, AV411
Placebo Comparator: Placebo Placebo oral BID 7 days (0mg ibudilast)	Drug: Ibudilast Placebo oral BID 7 days Other Names: Sugar pill

Arm

Intervention/Treatment

Active Comparator: Ibudilast 20mg BID

Ibudilast 20mg oral BID 7 days

Drug: Ibudilast

Ibudilast oral 20mg BID for 7 days

Other Names:

MN166, AV411

Active Comparator: Ibudilast 50mg BID

Ibudilast 50mg oral BID 7 days

Drug: Ibudilast

Ibudilast oral 50mg BID for 7 days

Other Names:

MN166, AV411

Placebo Comparator: Placebo

Placebo oral BID 7 days (0mg ibudilast)

Drug: Ibudilast

Placebo oral BID 7 days

Other Names:

Sugar pill

Outcome Measures

Primary Outcome Measures

Number of Participants with Adverse Events as a Measure of Safety and Tolerability [35 days]
Number of Participants with Clinically Significant Changes in Cardiovascular Parameters as a Measure of Safety and Tolerability [35]

Secondary Outcome Measures

Number of participants with adverse outcomes on (1) VAS, drug-effect scale, subjective effects, etc., and (2) pharmacokinetics of methamphetamine as measures of efficacy [35 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

NOT seeking treatment for methamphetamine problems;
English-speaking;
Age 18-55;
Meet SCID criteria for MA dependence;
Self-reported history of MA use via injection or smoking AND at least one MA positive urine drug screening during eligibility;
Resting heart rate 50-100BPM; Systolic BP 105-150 mm Hg; Diastolic BP 45-90 mm Hg stabilized within 2 days of admission;
Baseline EKG demonstrating normal sinus rhythm, normal conduction, no clinically significant arrhythmias;
Use of acceptable barrier method of birth control;
If female, not pregnant or lactating;
Have medical history and physical examination demonstrating no additional clinically significant contraindications for study participation, in judgment of investigators.

Exclusion Criteria:

Current dependence on cocaine, opioids, marijuana, or alcohol;
Liver function tests GE 3x upper limit of normal, or kidney function tests GE 2x the upper limit of normal;
Current or past history of seizure disorder;
History of head trauma;