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

October 11, 2016 updated by: New York State Psychiatric Institute

The Safety, Tolerability and Preliminary Efficacy of AV411, a Glial Activation Inhibitor, in Heroin Abusers Under Conditions of Morphine Maintenance and Withdrawal

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10032
        • New York State Psychiatric Institute/Columbia University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
This group will receive placebo drug
Drug: Placebo (PCB)
Placebo drug will be administered orally twice a day (BID) for two consecutive weeks
Other Names:
  • PCB or 0 mg
Experimental: Low-dose AV411
This group will receive a low dose of AV411
Drug: AV411
Low (20 mg), and high dose (40 mg) of AV411 will be administered orally twice a day (BID) for two consecutive weeks
Other Names:
  • ibudilast
Experimental: High-dose AV411
This group will receive a high dose of AV411
Drug: AV411
Low (20 mg), and high dose (40 mg) of AV411 will be administered orally twice a day (BID) for two consecutive weeks
Other Names:
  • ibudilast

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Subjective Opioid Withdrawal Scale Score (SOWS)
Time Frame: Measured at the end of each two-week maintenance period (i.e., Placebo, Low AV411, High AV411).
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Effects of AV411 on the Analgesic Effects of Oxycodone.
Time Frame: Measured at the end of each AV411 of the three two-week maintenance periods
The McGill Pain Questionnaire (Melzack, 1987) was used to assess pain experience immediately following the immersion of the hand in 4 degree Celsius water. Scores were added across all 15 items to generate a sum score, which ranged between 15 and 60. Larger scores indicate greater pain levels.
Measured at the end of each AV411 of the three two-week maintenance periods

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

New York State Psychiatric Institute

Collaborators

National Institute on Drug Abuse (NIDA)

Investigators

  • Principal Investigator: Sandra D Comer, PhD, New York State Psychiatric Institute and Columbia University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2008

Primary Completion (Actual)

April 1, 2010

Study Completion (Actual)

June 1, 2012

Study Registration Dates

First Submitted

July 24, 2008

First Submitted That Met QC Criteria

July 24, 2008

First Posted (Estimate)

July 28, 2008

Study Record Updates

Last Update Posted (Estimate)

December 5, 2016

Last Update Submitted That Met QC Criteria

October 11, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • #5725
  • P50DA009236 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Data have been published in a peer-reviewed journal.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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