Biomarkers of Injectable Extended Release Naltrexone Treatment

Study Overview
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Brief Summary
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This study evaluates the biological markers of treatment of opioid dependent individuals with an extended release formulation of the opioid antagonist naltrexone. The biological measures include functional MRI, blood levels of naltrexone and its metabolites, urine toxicology and behavioral tests probing various aspects of personality, memory, reward processing and attention.

Detailed Description
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This study is using blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) to examine the brain predictors of adherence and outcomes of opioid antagonist therapy. Opioid-dependent intravenous heroin users are offered up to 3 monthly injections of the extended-release naltrexone (XRNTX) contingent upon successful outpatient non-opioid detoxification, with an additional 4 weeks of follow up. Brain responses to heroin-related pictures are recorded using fMRI prior to the 1st XRNTX injection and approximately 2 weeks thereafter the 1st XRNTX injection. Primary clinical variables include the number of injections (maximum of 3) accepted by participants, change in self-reported craving for opioids after exposure to drug-related visual cues during the brain fMRI sessions, urine levels of ten commonly abused substances and self-report of cigarette use.

Official Title
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Biomarkers of Disease and Response to Treatment in Opioid Addiction

Conditions
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Heroin Dependence, Opioid Dependence

Intervention / Treatment
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* Drug: Naltrexone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DSM-IV-TR diagnosis of opioid dependence, active opioid use, confirmed by urine toxicology screen and self-reported monthly intravenous heroin use for more than 2 weeks in the past 3 months urine toxicology screen negative for opioids after detoxification good physical health as indicated by history and physical examination, screening blood work-up and urinalysis. Exclusion Criteria: chronic medical illnesses; current use of medications potentially confounding brain activity, such as anti-dopaminergic agents, anti-depressants and beta-blockers; current DSM-IV-TR Axis I psychiatric disorders other than opioid and nicotine dependence; life time history of concurrent IV cocaine and heroin (speedball) administration; pregnancy or breastfeeding; history of clinically significant head trauma; contraindications for naltrexone treatment including medical conditions requiring opioid analgesics, e.g. chronic pain or planned surgery, obesity, elevated liver enzymes (> 3 times upper limit of normal), failure to complete opioid detoxification contraindications for MRI, i.e. indwelling magnetically active foreign bodies and phobia to enclosed spaces

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Naltrexone Intervention<br>Eligible participants receive up to three monthly injections of 380 mg of naltrexone contained in dissolvable polymer microspheres and administered by deep intramuscular injection and slowly released over a period of approximately 4 weeks. | Drug: Naltrexone<br>* Up to three monthly injections of 380 mg of naltrexone suspended in dissolvable polymer microspheres and administered intramuscularly<br>* Other names: Vivitrol ®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain response to heroin-related visual cues | Brain, behavioral and motivational (e.g. craving) response to audiovisual drug-related and control stimuli (images, smells and sounds) and to standard tasks of decision making, self-appraisal, response inhibition, social interaction and reward processing. | 1 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cigarettes smoked per day | behavioral | 6 months | 
| Urine toxicology | Urine toxicology for methamphetamine, amphetamines, cannabis, cocaine, oxycodone, buprenophine, methadone, opioids, benzodiazepines and barbiturates. | 6 months | 
| Injections | Number of injections (maximum of 3) accepted by participants | 3 months | 
| Motivational response to opioid-related visual cues measured by self-reported craving for opioids | Change in self-reported craving for opioids after exposure to opioid-related visual cues during functional MRI sessions | 2 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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opioid, naltrexone, neuroimaging, heroin, addiction, dependence, Vivitrol®, functional magnetic resonance imaging