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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00723177
Recruitment Status : Completed
First Posted : July 28, 2008
Results First Posted : December 5, 2016
Last Update Posted : December 5, 2016
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
New York State Psychiatric Institute

Tracking Information
First Submitted Date  ICMJE July 24, 2008
First Posted Date  ICMJE July 28, 2008
Results First Submitted Date  ICMJE March 23, 2015
Results First Posted Date  ICMJE December 5, 2016
Last Update Posted Date December 5, 2016
Study Start Date  ICMJE October 2008
Actual Primary Completion Date April 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 11, 2016)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 24, 2008)
Total Subjective Opioid Withdrawal Scale score [ Time Frame: Twice daily for the duration of the trial ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 11, 2016)
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.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 24, 2008)
Pupil diameter, heart rate, blood pressure, respiratory rate, body temperature, other subjective measures, plasma levels of AV411 [ Time Frame: Various time points throughout trial ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Phase IIa Study of AV411, a Glial Activation Inhibitor, for Opioid Withdrawal
Official Title  ICMJE The Safety, Tolerability and Preliminary Efficacy of AV411, a Glial Activation Inhibitor, in Heroin Abusers Under Conditions of Morphine Maintenance and Withdrawal
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE Opioid-Related Disorders
Intervention  ICMJE
  • 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 Name: ibudilast
  • Drug: Placebo (PCB)
    Placebo drug will be administered orally twice a day (BID) for two consecutive weeks
    Other Name: PCB or 0 mg
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    This group will receive placebo drug
    Intervention: Drug: Placebo (PCB)
  • Experimental: Low-dose AV411
    This group will receive a low dose of AV411
    Intervention: Drug: AV411
  • Experimental: High-dose AV411
    This group will receive a high dose of AV411
    Intervention: Drug: AV411
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 24, 2008)
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 2012
Actual Primary Completion Date April 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00723177
Other Study ID Numbers  ICMJE #5725
P50DA009236 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Data have been published in a peer-reviewed journal.
Responsible Party New York State Psychiatric Institute
Study Sponsor  ICMJE New York State Psychiatric Institute
Collaborators  ICMJE National Institute on Drug Abuse (NIDA)
Investigators  ICMJE
Principal Investigator: Sandra D Comer, PhD New York State Psychiatric Institute and Columbia University
PRS Account New York State Psychiatric Institute
Verification Date October 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP