Phase IIa Study of AV411, a Glial Activation Inhibitor, for Opioid Withdrawal - Full Text View

Purpose

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.

Condition	Intervention	Phase
Opioid-Related Disorders	Drug: AV411	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Outcomes Assessor) Primary Purpose: Basic Science
Official Title:	The Safety, Tolerability and Preliminary Efficacy of AV411, a Glial Activation Inhibitor, in Heroin Abusers Under Conditions of Morphine Maintenance and Withdrawal

Further study details as provided by New York State Psychiatric Institute:

Primary Outcome Measures:

Total Subjective Opioid Withdrawal Scale score [ Time Frame: Twice daily for the duration of the trial ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Pupil diameter, heart rate, blood pressure, respiratory rate, body temperature, other subjective measures, plasma levels of AV411 [ Time Frame: Various time points throughout trial ] [ Designated as safety issue: Yes ]

Enrollment:	30
Study Start Date:	October 2008
Estimated Study Completion Date:	December 2013
Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: Placebo This group will receive placebo AV411	Drug: AV411 Placebo, low, and high dose of AV411 will be administered orally BID for two consecutive weeks Other Name: ibudilast
Experimental: Low-dose AV411 This group will receive a low dose of AV411	Drug: AV411 Placebo, low, and high dose of AV411 will be administered orally BID for two consecutive weeks Other Name: ibudilast
Experimental: High-dose AV411 This group will receive a high dose of AV411	Drug: AV411 Placebo, low, and high dose of AV411 will be administered orally BID for two consecutive weeks Other Name: ibudilast

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.

Eligibility

Ages Eligible for Study:	21 Years to 45 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Adults between the ages of 21 and 45
Current dependence on heroin according to 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, PhD, Lippincott Williams and Wilkins, NY 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00723177

Locations

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

Sponsors and Collaborators

New York State Psychiatric Institute

National Institute on Drug Abuse (NIDA)

Investigators

Principal Investigator:

Sandra D Comer, PhD

New York State Psychiatric Institute and Columbia University

More Information

No publications provided

Responsible Party:	New York State Psychiatric Institute
ClinicalTrials.gov Identifier:	NCT00723177 History of Changes
Other Study ID Numbers:	#5725, P50DA009236, P50 DA009236
Study First Received:	July 24, 2008
Last Updated:	December 18, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by New York State Psychiatric Institute:

opioid withdrawal, analgesia

Additional relevant MeSH terms:

Opioid-Related Disorders
Substance-Related Disorders
Mental Disorders
Analgesics, Opioid
Analgesics
Sensory System Agents

Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Central Nervous System Depressants

ClinicalTrials.gov processed this record on May 16, 2013