Phase IIa Study of AV411, a Glial Activation Inhibitor, for Opioid Withdrawal

NCT00723177 | Completed Phase 2 Results

• 2 other identifiers: #5725P50DA009236
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Repeated use and/or abuse of opioid medications is generally associated with a characteristic withdrawal syndrome that develops after cessation of drug administration. The present study is designed to evaluate the effectiveness of AV411 to alter opioid-induced withdrawal symptoms.

Conditions

Opioid-Related Disorders

Keywords

opioid withdrawal, analgesia

Outcome Measures

Primary Outcomes (1)

• Subjective Opioid Withdrawal Scale Score (SOWS)

  Measures severity of opioid withdrawal in opioid dependent populations (0-64). Larger values indicate more severe withdrawal.

  Measured at the end of each two-week maintenance period (i.e., Placebo, Low AV411, High AV411).

Secondary Outcomes (1)

• The Effects of AV411 on the Analgesic Effects of Oxycodone.

  Measured at the end of each AV411 of the three two-week maintenance periods

Study Arms (3)

Placebo

PLACEBO COMPARATOR

This group will receive placebo drug

Drug: Placebo (PCB)

Low-dose AV411

EXPERIMENTAL

This group will receive a low dose of AV411

Drug: AV411

High-dose AV411

EXPERIMENTAL

This group will receive a high dose of AV411

Drug: AV411

Interventions

AV411 DRUG

Low (20 mg), and high dose (40 mg) of AV411 will be administered orally twice a day (BID) for two consecutive weeks

Also known as: ibudilast

High-dose AV411; Low-dose AV411

Placebo (PCB) DRUG

Placebo drug will be administered orally twice a day (BID) for two consecutive weeks

Also known as: PCB or 0 mg

Placebo

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Adults between the ages of 21 and 45
• Current dependence on heroin according to (Diagnostic and Statistical Manual) DSM-IV criteria
• Non-treatment seeking

You may not qualify if:

• Female participants who are currently pregnant or breastfeeding. Lack of effective birth control 10 days before Study Day 1 (15 days prior to the first PET scan)
• Self-reported use of methadone, buprenorphine, or levo-alpha-acetylmethadol (LAAM) in the past 14 days
• Participants who have a positive history of neurological illness (including epilepsy) or those who have received anti-convulsant 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 along with a clinical history and chest X-ray indicative of active tuberculosis. (Individuals who have a positive PPD test and have a negative chest X-ray, are not symptomatic for tuberculosis, and do not require anti-tuberculosis 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 a chest X-ray and clinical history will be used for evaluation purposes).
• Presence or positive history of severe medical illness or any cardiovascular disease or heart abnormality, such as low hemoglobin (Hb \< 13 g/dL in males, Hb \< 11 g/dL in females), or BP \> 150/90.
• Requirement for any of the following medications (current or within the past 4 weeks): psychotropics (including sedative/hypnotics, antidepressants, neuroleptics), anticonvulsants, antihypertensives, antiarrhythmics, or antiretroviral medications,. Participants on any current psychoactive prescription medications will be excluded.
• Current dependence (by DSM-IV criteria) on methadone, LAAM, or buprenorphine
• 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
• Participants who are positive for HIV or chronic active hepatitis
• Metal implants or paramagnetic objects contained within the body which may interfere with the MRI scan, as determined in consultation with a neuroradiologist and according to the guidelines set forth in the following reference book commonly used by neuroradiologists: "Guide to MR procedures and metallic objects" Shellock Frank G., Lippincott Williams \& Wilkins Healthcare, Philadelphia, 2001.

Sponsors & Collaborators

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

Study Sites (1)

New York State Psychiatric Institute/Columbia University

New York, New York, 10032, United States

Location

Related Publications (2)

• Cooper ZD, Johnson KW, Pavlicova M, Glass A, Vosburg SK, Sullivan MA, Manubay JM, Martinez DM, Jones JD, Saccone PA, Comer SD. The effects of ibudilast, a glial activation inhibitor, on opioid withdrawal symptoms in opioid-dependent volunteers. Addict Biol. 2016 Jul;21(4):895-903. doi: 10.1111/adb.12261. Epub 2015 May 14.

  PMID: 25975386 RESULT

• 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; Agnosia

Interventions

ibudilast

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Sandra Comer PhD
• Organization: NYSPI/Columbia University

SDC10@columbia.edu

646 774-6146

Study Officials

• Sandra D Comer, PhD

  New York State Psychiatric Institute and Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2008
• First Posted: July 28, 2008
• Study Start: October 1, 2008
• Primary Completion: April 1, 2010
• Study Completion: June 1, 2012
• Last Updated: December 5, 2016
• Results First Posted: December 5, 2016

Record last verified: 2016-10

Data Sharing

• IPD Sharing: Will share

Locations

US (1)