The Safety, Tolerability and Preliminary Efficacy of AV411, a Glial Activation Inhibitor, in Heroin Abusers Under Conditions of Morphine Maintenance and Withdrawal
Overview
- Phase
- Phase 2
- Intervention
- Placebo (PCB)
- Conditions
- Opioid-Related Disorders
- Sponsor
- New York State Psychiatric Institute
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Subjective Opioid Withdrawal Scale Score (SOWS)
- Status
- Completed
- Last Updated
- 9 years ago
Overview
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.
Investigators
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/
- •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
Arms & Interventions
Placebo
This group will receive placebo drug
Intervention: Placebo (PCB)
Low-dose AV411
This group will receive a low dose of AV411
Intervention: AV411
High-dose AV411
This group will receive a high dose of AV411
Intervention: AV411
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- The Effects of AV411 on the Analgesic Effects of Oxycodone.(Measured at the end of each AV411 of the three two-week maintenance periods)