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

NCT ID: NCT00723177

Last Updated: 2016-12-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2012-06-30

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.

Detailed Description

Opioid-induced cytokine release and glial activation has been proposed to directly contribute to the affective and physiological aspects of withdrawal. Furthermore, cytokine release following opioid administration has been hypothesized to be a limiting factor in both the duration and magnitude of opioid-induced analgesia. The two primary goals of our study are to assess AV411's ability to 1) reduce the opioid-withdrawal syndrome and 2) increase and prolong the analgesic effects of the mu-opioid agonist, oxycodone. To explore whether AV411 decreases opioid-induced glial cell activation, some participants assigned to the placebo and high dose AV411 groups (n = 6 for each dose condition) will be studied twice with [11C]PK11195, a positron emission tomography (PET) radiotracer used to measure the peripheral benzodiazepine receptor (PBR) in the human brain. The PBR is a receptor located on the mitochondria of the microglia and can be used to examine microglial activation in various brain regions.

Conditions

Opioid-Related Disorders

Keywords

opioid withdrawal, analgesia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Placebo

This group will receive placebo drug

Group Type: PLACEBO_COMPARATOR

Placebo (PCB)

Intervention Type: DRUG

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

Low-dose AV411

This group will receive a low dose of AV411

Group Type: EXPERIMENTAL

AV411

Intervention Type: DRUG

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

High-dose AV411

This group will receive a high dose of AV411

Group Type: EXPERIMENTAL

AV411

Intervention Type: DRUG

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

Interventions

AV411

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

Intervention Type: DRUG

Placebo (PCB)

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

Intervention Type: DRUG

Other Intervention Names

ibudilast; PCB or 0 mg

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• 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.
• Lifetime exposure to radiation in the workplace, or participation in nuclear medicine procedures, including research protocols, in the past year
• Positive Allen Test indicating lack of collateral blood flow to hand
• History of Reynaud's syndrome

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

New York State Psychiatric Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sandra D Comer, PhD

Role: PRINCIPAL_INVESTIGATOR

New York State Psychiatric Institute and Columbia University

Locations

New York State Psychiatric Institute/Columbia University

New York, New York, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 25975386 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25175864 (View on PubMed)

Other Identifiers

P50DA009236

Identifier Type: NIH

Identifier Source: secondary_id

View Link

#5725

Identifier Type: -

Identifier Source: org_study_id