The Separate and Combined Effects of Vivitrol and Opiate Abstinence Reinforcement in the Treatment of Opioid Dependence

Study Overview
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Brief Summary
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In this 5-year study, the investigators propose to evaluate the separate and combined effects of the FDA-approved formulation of extended release naltrexone (Vivitrol®) and employment-based reinforcement of opiate abstinence in promoting opiate abstinence and reducing risky injection behavior in recently detoxified, opioid-dependent, injection drug users.

Detailed Description
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Injection heroin use is a chronic problem that fuels the transmission of HIV/AIDS through risky injection behaviors. Methadone and buprenorphine can reduce heroin use and risky injection behavior; however, they have abuse potential, produce physical dependence, can produce lethal overdose, are highly regulated, and some patients simply do not want agonist treatment. Opiate detoxifications can serve as an alternative to agonist treatment, but many injection drug users relapse to heroin use and resume risky injection behaviors after detoxification. Vivitrol®, an extended release formulation of naltrexone, was recently approved by the FDA for the treatment of opioid dependence, but its clinical utility is uncertain given the reluctance of many opioid-dependent adults to maintain its long-term use, and the fact that some patients continue to use opiates while under naltrexone blockade. The investigators research in the first period of this grant showed that employment-based reinforcement can be highly effective in promoting long-term adherence to Vivitrol®. Employment-based reinforcement may be ideally suited to address the limitations of extended release naltrexone by capitalizing on its potential to simultaneously reinforce naltrexone adherence and opiate abstinence. This grant will evaluate the effectiveness of employment-based reinforcement to simultaneously promote high rates of Vivitrol® adherence and increase opiate abstinence. After an opioid detoxification and induction onto oral naltrexone, participants will be invited to attend the Therapeutic Workplace for 24 weeks (where they can work and earn wages) and will be randomly assigned to one of four groups that will differ in whether they receive Vivitrol®, employment-based opiate abstinence reinforcement, both or neither. Participants in Vivitrol® conditions will be required to take scheduled injections to work and earn wages. Participants exposed to opiate abstinence reinforcement will receive a temporary decrease in their workplace pay if they fail to provide an opiate-free urine sample. The study will assess the effects of the interventions on weekly opiate urinalysis results, and on measures of injection drug use and cocaine use. If this study shows that the combined use of Vivitrol® and employment-based reinforcement of adherence and opiate abstinence is effective in maintaining long-term opiate abstinence, this model of employment-based addiction pharmacotherapy could be integrated into community workplaces to disseminate the effective use of Vivitrol®; it could be used to enhance the utility of other new antagonist-like addiction medications; and it could provide an effective means of reducing injection drug use in individuals who persist in injecting heroin and exposing themselves and others to the risk of acquiring or transmitting HIV infection due to their continued injection drug use and risky injection behaviors.

Official Title
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The Separate and Combined Effects of Vivitrol and Opiate Abstinence Reinforcement in the Treatment of Opioid Dependence

Conditions
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Opioid Dependence

Intervention / Treatment
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* Drug: Vivitrol
* Behavioral: Employment-based opiate abstinence reinforcement
* Other: Usual Care Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: meet the DSM-IV criteria for opioid dependence, report using heroin at least 21 of the last 30 days while living in the community, are unemployed, are 18-65 years old, are medically approved for naltrexone, live in or near Baltimore, MD. Exclusion Criteria: have current DSM-IV major Axis I disorders have current suicidal or homicidal ideation express interest in methadone treatment are required to use opioids for medical purposes earned over $200 in taxable income over the previous 30 days while living in the community have physical limitations that prevent them from using a keyboard are pregnant or breastfeeding have serum aminotransferase levels over three times normal have known intolerance and/or hypersensitivity to naltrexone, carboxymethylcellulose, or poly (lactide-co-glycolide) (PLG) or any other components of the diluents; are participating in any other clinical study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vivitrol Only<br>The VIVITROL group will be offered one injection of VIVITROL every 4 weeks. Participants in the VIVITROL group will be required to take their scheduled injections to work and earn wages. If a participant misses a scheduled VIVITROL injection (more than 3 days from the scheduled date of administration), the participant will not be allowed to work until the injection is accepted. Additionally, missing a scheduled injection will result in a base pay reset from $8 per hour to $1 per hour. After the reset, the participant's base pay will increase by $1/hour to the maximum of $8/hour for every day that the participant works at least 5 minutes. | Drug: Vivitrol<br>* Participants receiving this intervention will receive the FDA-approved dose, route, and schedule of administration of VIVITROL. The dose of VIVITROL of 380 mg will be delivered intramuscularly every 4 weeks.<br>|
| Experimental: VIVITROL&Opiate Abstinence Reinforcement<br>This group will be offered VIVITROL and will be required to take it to attend the workplace and to maintain maximum pay. This group will also receive employment-based opiate abstinence reinforcement. This contingency will require participants to provide opiate-negative urine samples on M,W, and F to maintain their maximum pay. If a participant in this group provides an opiate-positive urine sample, or fails to provide a scheduled sample, their base pay will be reset from $8 per hour to $1 per hour. On each day after the reset that the participant provides a urine sample that meets the opiate abstinence criteria and attends the workplace for at least 5 minutes, their base pay will increase by $1 per hour until it reaches the maximum of $8 per hour. | Drug: Vivitrol<br>* Participants receiving this intervention will receive the FDA-approved dose, route, and schedule of administration of VIVITROL. The dose of VIVITROL of 380 mg will be delivered intramuscularly every 4 weeks.<br>Behavioral: Employment-based opiate abstinence reinforcement<br>* This intervention will require participants to provide opiate-negative urine samples on Monday, Wednesday and Friday to maintain their maximum pay. If a participant provides an opiate-positive urine sample, or fails to provide a scheduled sample, their base pay will be reset from $8 per hour to $1 per hour. On each day after the reset that the participant provides a urine sample that meets the opiate abstinence criteria and attends the workplace for at least 5 minutes, their base pay will increase by $1 per hour until it reaches the maximum of $8 per hour.<br>|
| Experimental: Opiate Abstinence Reinforcement Only<br>This group would receive employment-based opiate abstinence reinforcement, but this group will not receive VIVITROL. | Behavioral: Employment-based opiate abstinence reinforcement<br>* This intervention will require participants to provide opiate-negative urine samples on Monday, Wednesday and Friday to maintain their maximum pay. If a participant provides an opiate-positive urine sample, or fails to provide a scheduled sample, their base pay will be reset from $8 per hour to $1 per hour. On each day after the reset that the participant provides a urine sample that meets the opiate abstinence criteria and attends the workplace for at least 5 minutes, their base pay will increase by $1 per hour until it reaches the maximum of $8 per hour.<br>|
| Other: Usual Care Control<br>This group will receive neither abstinence reinforcement nor VIVITROL injections, but they will be invited to attend the workplace and outpatient drug abuse counseling. | Other: Usual Care Control<br>* Participants receiving this intervention will be invited to attend the workplace and outpatient drug abuse counseling.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Weekly Urine Samples Negative for Opiates | Was the participant's urine sample negative for opiates at each of the 24 weekly assessments scheduled after random assignment (Y/N)? The outcome measure was the percentage of weekly urine samples that was negative for opiates. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Weekly Urine Samples Negative for Cocaine | Was the participant's urine sample negative for cocaine at each of the 24 weekly assessments scheduled after random assignment (Y/N)? The outcome measure was the percentage of weekly urine samples that was negative for cocaine. | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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opioid use disorder, treatment, heroin, extended-release naltrexone, incentives, cotningency management, employment-based reinforcement, therapeutic workplace