Effects of Ibudilast on Oxycodone Self-administration in Opioid Abusers

NCT01740414 | Completed Phase 2 Results

• 2 other identifiers: #6021P50DA009236
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Opioid Abuse; Opioid Dependence

Keywords

prescription opioid abuse; pain; opioid withdrawal; oxycodone; ibudilast

Outcome Measures

Primary Outcomes (1)

• Drug Self-administration Breakpoint

  Participants are allowed to perform an operant task (click on a mouse) in order to receive a dose drug under investigation (oxycodone dose 0 mg, 15 mg, or 30 mg). The drug breakpoint is the maximum number of responses (mouse clicks) the participant was willing to make to receive the drug. Within the context of abuse liability studies, larger breakpoints represent greater abuse potential of a drug.

  42 days

Secondary Outcomes (1)

• Positive Subjective Effects to Oxycodone

  42 days

Other Outcomes (1)

• Pain Intensity

  42 days

Study Arms (2)

MN-166 (formerly AV411) First

ACTIVE COMPARATOR

Participants who began 14-day maintenance on MN-166 (50 mg) first, before switching to Placebo maintenance.

Drug: MN-166 (50 mg) First

Placebo First

PLACEBO COMPARATOR

Participants who began 14-day maintenance on Placebo first, before switching to MN-166 (50 mg) maintenance.

Drug: Placebo First

Interventions

MN-166 (50 mg) First DRUG

In this arm of the study participants were first maintained on 50 mg MN-166 BID for approximately 14 days, and were then switched onto placebo maintenance. The subjective and analgesic effects of Oxycodone (0 mg, 15 mg and 30 mg) were tested under each of the two maintenance conditions (Placebo \& MN-166).

Also known as: ibudilast/AV411

MN-166 (formerly AV411) First

Placebo First DRUG

This arm of the study participants were first maintained on placebo for approximately 14 days, and were then switched onto 50mg MN-166 BID maintenance. . The subjective and analgesic effects of Oxycodone (0 mg, 15 mg and 30 mg) were tested under each of the two maintenance conditions (Placebo \& MN-166).

Also known as: placebo

Placebo First

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adults between the ages of 21 and 55
• Current opioid dependence according to DSM-IV criteria
• currently not seeking treatment

You may not qualify if:

• 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 \< 13 gm/dL in males, Hb \< 11 gm/dL in females) with evidence of acute or chronic blood loss, or BP \> 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).

Sponsors & Collaborators

• New York State Psychiatric Institute: lead
• National Institute on Drug Abuse (NIDA): collaborator
• MediciNova: collaborator

Study Sites (1)

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

Related Publications (1)

• Jacobsen JH, Watkins LR, Hutchinson MR. Discovery of a novel site of opioid action at the innate immune pattern-recognition receptor TLR4 and its role in addiction. Int Rev Neurobiol. 2014;118:129-63. doi: 10.1016/B978-0-12-801284-0.00006-3.

  PMID: 25175864 DERIVED

MeSH Terms

Conditions

Opioid-Related Disorders; Pain

Interventions

ibudilast

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Sandra Comer
• Organization: New York State Psychiatric Institute

comersd@nyspi.columbia.edu

646-774-6146

Study Officials

• Sandra D Comer, PhD

  Department of Psychiatry, Columbia University and NYSPI

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2012
• First Posted: December 4, 2012
• Study Start: November 1, 2012
• Primary Completion: December 1, 2015
• Study Completion: May 1, 2017
• Last Updated: August 17, 2017
• Results First Posted: August 17, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will share

Locations

US (1)