Phase 2
N=28
Effects of Ibudilast on Oxycodone Self-administration in Opioid Abusers
Opioid Abuse · Opioid Dependence
Bottom Line
View on ClinicalTrials.gov: NCT01740414 ↗Enrolled (actual)
28
Serious AEs
0.0%
Results posted
Aug 2017
Primary outcome: Primary: Drug Self-administration Breakpoint — 347; 363; 1472; 43 Clicks on a computer mouse
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- MN-166 (50 mg) First (Drug); Placebo First (Drug)
- Age
- Adult · 21+ yrs
- Sex
- All
- Sponsor
- New York State Psychiatric Institute
- Primary completion
- Dec 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Drug Self-administration Breakpoint |
347; 363; 1472; 43; 1650; 2459 | — |
| SECONDARY Positive Subjective Effects to Oxycodone |
.8; 10.9; 24.2; .9; 15.5; 22.7 | — |
Summary
Opioid drugs increase glial cell activation which may be related to the abuse liability of opioid drugs. Data supporting this hypothesis have demonstrated that glial cell attenuators decrease the positive rewarding aspect of opioids in laboratory animals. Ibudilast (MN-166, formerly AV411) is a compound that inhibits the activation of glia. Recent preclinical studies demonstrate that while ibudilast increases the analgesic effects of opioids, it decreases the rewarding effects of such drugs. It has also been shown that ibudilast suppresses morphine-induced release of dopamine, a primary neurotransmitter involved in the rewarding and reinforcing effects of abused drugs. Additionally, we recently found that ibudilast decreases subjective symptoms of opioid withdrawal in opioid dependent humans during detoxification.
Therefore, the primary aim of this 6-7 week inpatient study is to investigate the ability of MN-166 to dose-dependently alter the reinforcing, analgesic, subjective, performance, and physiological effects of oxycodone, a commonly abused prescription opioid.
This study includes a 10-day morphine taper phase, followed by two study phases (approximately 18 days each) with daily active ibudilast and placebo administration, respectively. After the detoxification phase, participants are randomized to receive placebo or MN-166, and then be stabilized on the medication. Thereafter, participants will complete laboratory sessions. Subsequently, during Phase 2, participants will cross over to the other treatment arm, stabilize, and complete laboratory sessions.
Eligibility Criteria
Inclusion Criteria
- Adults between the ages of 21 and 55
- Current opioid dependence according to DSM-IV criteria
- currently not seeking treatment
Exclusion Criteria
- Female patients that are currently pregnant, or breastfeeding. Lack of effective birth control.
- Participants who have a positive history of neurological illness (including epilepsy) or those who have received anticonvulsant therapy during the past 5 years.
- Liver disease requiring medication or medical treatment, and/or aspartate or alanine aminotransferase levels greater than 3 times the upper limit of normal.
- Gastrointestinal or renal disease that would significantly impair absorption, metabolism or excretion of study drug, or require medication or medical treatment.
- Neurological or psychiatric disorders including psychosis, bipolar disorder, organic brain disease, any seizure history or other disorders that require treatment or that could make study compliance difficult.
- Positive tuberculosis (PPD) TB skin test, clinical history, and chest X-ray indicative of active tuberculosis. (Individuals with a positive PPD test and negative chest X-ray who are not symptomatic for tuberculosis, and do not require antituberculosis therapy will be eligible to participate. Participants will be asked if they ever tested positive for tuberculosis. If so, they will not be given a PPD and chest X-ray and clinical history will be used for evaluation purposes).
- Presence or positive history of severe medical illness or cardiovascular disease or heart abnormality, such as low hemoglobin (Hb 140/90.
- Participants on any current psychoactive prescription medications that may interfere with the study measures.
- Current physical dependence on any substance, other than opioids, nicotine or caffeine (ex., methadone, benzodiazepines, LAAM, marijuana, alcohol, etc.).
- Participants for whom detoxification is not "clinically recommended" such as those with a significant history of overdose following detoxification.
- Participation in an investigational drug study within the past 3 months.
- Hypersensitivity to any of the medications used in this study.
- Current (within the last 3 months) chronic pain.
- Platelet and white blood cell count that are not within the normal range (platelet = 120 x103/μl -400 x103/μl; WBC= 3.5 x106/μl -10.8x106/μl).
- Use of Theophylline (PDE-3 inhibitor) or Roflumilast (PDE-4 inhibitor).
Data sourced from ClinicalTrials.gov (NCT01740414). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.