Feasibility Study of Extended-release Naltrexone (Vivitrol) in Drug Court Settings

Study Overview
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Brief Summary
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In preparation for a large-scale randomized controlled trial (RCT) of Vivitrol® effectiveness in drug courts, investigators propose a feasibility study in the Wake County, North Carolina drug court, where an estimated 50% of clients are opioid dependent. Aim 1: Pilot RCT. Pilot-test the delivery of Vivitrol® treatment for 10-20 interested and eligible clients of the Wake County Drug Court.

Detailed Description
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Aim 1. Pilot RCT. The pilot delivery of Vivitrol® in the Wake County Drug Court will be carried out with 20-40 eligible drug court clients under treatment by Fellowship Health Resources, Inc. (FHR), the community behavioral health treatment agency that is the contracted treatment provider for the Wake County Drug Court. Participants will be randomized in equal number to receive Vivitrol® plus treatment as usual (TAU) or TAU only. TAU for drug court clients receiving services at FHR includes psychosocial treatment such as individual or group therapy, and sometimes also oral naltrexone for clients who are medically eligible and interested in taking the medication, the cost of which is covered by the agency for uninsured clients. (FHR currently administers Vivitrol® for a small number of interested agency clients with health insurance that covers the medication; the vast majority of their drug court clients are uninsured and so have no real access to the extended-release formulation due to its high cost.) Vivitrol® is an FDA-approved extended-release injectable form of naltrexone. Naltrexone is also available in oral, but not extended release, form. Naltrexone is an opioid antagonist that blocks opioid receptors in the brain to stop pleasurable feelings associated with taking opioids. Potentially eligible subjects will be drug court-referred FHR clients willing and eligible to take Vivitrol®, and willing to be randomly assigned to Vivitrol® or TAU. Potential subjects already under treatment with oral naltrexone at FHR would be eligible to enter the study if willing to switch to injectable Vivitrol® if randomly assigned. Study subjects who are randomized to Vivitrol® would receive a once-monthly injection of Vivitrol® for 12 months, or less if they decide to stop receiving Vivitrol® or to drop out of the study. Those randomized to TAU would continue with treatment as before, which could including (1) staying on oral naltrexone if already on it, (2) considering starting oral naltrexone, if interested, or (3) continuing with psychosocial treatment only. The Vivitrol® will be administered by study medical personnel at FHR. Randomization to the Vivitrol® arm would add urine pregnancy testing to FHR's existing Vivitrol® medical evaluation protocol and consent process, which currently screens for pregnancy without requiring a urine test. A urine pregnancy test will be administered once per month for female study participants of child-bearing age who are in the Vivitrol® group. All drug court clients, including study participants in both study groups, have urine drug tests at least once per week as part of program participation. In addition to participating in Vivitrol® and psychosocial treatment, pilot RCT participants will provide consent for FHR and the drug court to share information with the study team about their demographic and clinical characteristics, treatment participation (e.g., outpatient group therapy), and court-related events (e.g., type of conviction that led to their drug court participation, missed drug court appointments, sanctions for program violations, and the results of drug screens). Participants will also provide two face-to-face interviews at baseline and 6 months after baseline, about their interest and experience in Vivitrol® and/or other medication-assisted treatment (MAT), other treatment preferences, level of functioning, quality of life, and engagement in employment or education. Outcome measures include treatment participation, compliance with drug court conditions, arrests and incarcerations, treatment satisfaction, and self-reported subjective measures of functioning and quality of life. If a participant chooses not to participate in the study at any time, it will not affect his/her relationship with the court, FHR, right to health care, or participation in the study interview data collection. Site staff will follow participants for the purposes of collecting research and safety information. Investigators discontinue Vivitrol® or oral naltrexone in circumstances such as: adverse reactions to the medication; a change in medical status that makes it unsafe for a participant to continue receiving the medication, including pregnancy; or a participant becoming ill during the study. Participants who discontinue Vivitrol® or oral naltrexone for any reason may continue to participate in interviews for the study.

Official Title
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A Feasibility Study for Testing the Effects of Extended-release Naltrexone (Vivitrol) on Recidivism and Other Participant Outcomes in Drug Court Settings

Conditions
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Opioid-Related Disorders

Intervention / Treatment
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* Drug: Naltrexone for extended-release injectable suspension
* Drug: Oral naltrexone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Client of Wake County Drug Treatment Court Interested in medication-assisted treatment for opioid dependence 18-65 years old understands and speaks English understands that study participation is fully voluntary, with no effect on court standing willing and able to give written informed consent has an opioid use disorder (DSM-5 diagnosis of moderate or severe opioid use disorder) has at least 6 months remaining before anticipated Drug Court graduation (if female) does not intend to become pregnant or breastfeeding during the study period and is willing to adhere to contraception requirements during the study period is willing to adhere to the study requirements Has at least 7-10 days without opioid use before beginning extended-release injectable naltrexone given that detoxification from opioids before initiating or resuming extended-release injectable naltrexone is necessary to prevent withdrawal. Exclusion Criteria*: Is pregnant (i.e., has a positive pregnancy test), planning to become pregnant, or breastfeeding during the study Has a positive urine drug test for opioids, buprenorphine or methadone at the beginning of treatment and before each Vivitrol® injection Has used any opioid drug within 10 days prior to treatment Has a condition, disease state, previous medical history, or observed abnormalities (including physical examination, laboratory evaluation [e.g., kidney or liver function test result], or urinalysis finding) at screening that, in the opinion of the investigator, would preclude safe participation in the study or affect the ability of the subject to adhere to the protocol visit schedule, fulfill visit requirements, or would interfere with the study assessments, including, but not limited to, the following: Uncontrolled hypertension, uncontrolled diabetes, renal disease/impairment, stroke, seizures or neurological disorder, cardiovascular (eg, endocarditis), neoplastic disease Chronic pain condition requiring ongoing opioid analgesia Aspartate aminotransferase or alanine aminotransferase value ≥3 times the upper limit of normal Any contraindicated medical condition per the approved labeling for naltrexone Has had a DSM-5 diagnosis within the past 12 months of other psychiatric conditions or disorders that, in the investigator's opinion, could interfere with participation in the study Is currently physiologically dependent on any psychoactive substance (except caffeine, or tobacco) requiring medical intervention for detoxification Has a history of hypersensitivity or adverse reaction to naltrexone, or naloxone Has had significant suicidal ideation or behavior within the past year, as assessed with the Patient Health Questionnaire (PHQ-9) Note about exclusion criteria: If, after joining the study, a subject has a positive drug test, becomes pregnant, or acquires another exclusion condition that would have prevented him/her from joining the study, he or she may remain in the study but will not be permitted to receive Vivitrol®. Study staff will continue to gather interview data and administrative data on any enrolled, willing subjects.

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vivitrol<br>All drug court clients in the pilot RCT will receive standard psychosocial treatment for opioid dependence from FHR as part of their drug court program participation. Participants randomized to Vivitrol® will receive standard treatment along with monthly Vivitrol® injections administered by study staff at outpatient visits. Vivitrol® is naltrexone for extended-release injectable suspension. It is an injectable suspension containing 380 mg of naltrexone in a microsphere formulation and 4 mL diluent. The recommended dose of Vivitrol® is 380 mg delivered intramuscularly every 4 weeks or once a month. The injection should be administered by a healthcare provider as an intramuscular (IM) gluteal injection, alternating buttocks for each subsequent injection (see Links section of PRS for more information about Vivitrol). | Drug: Naltrexone for extended-release injectable suspension<br>* Opioid-dependent Drug Court clients enrolled in the study will receive monthly injections of Vivitrol for up to 12 months if they continue to be medically eligible and willing.<br>* Other names: Vivitrol;|
| Active Comparator: Oral naltrexone<br>Subjects randomized to oral naltrexone in addition to standard psychosocial treatment for opioid dependence from FHR as part of their drug court program participation. Oral naltrexone is the daily tablet formulation naltrexone that carries the same risks and benefits as the long-acting injectable formulation (Vivitrol®), except it does not have any of the risks related to injection (discomfort, potential for infection). Oral naltrexone is administered and provided by FHR to interested and eligible clients as part of the range of their usual care services. | Drug: Oral naltrexone<br>* Opioid-dependent Drug Court clients enrolled in the study will receive prescriptions for oral naltrexone for up to 12 months if they continue to be medically eligible and willing.<br>* Other names: Revia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With New Arrests | Any new arrests during the 12-month study period. This information will be collected from administrative records. | 12 months | 
| Number of Participants With New Incarcerations | Any new incarceration during the 12-month study period. This information will be collected from administrative records. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Positive Drug Screens | Number of times a client had a positive drug screen. This information will be collected from administrative records. | 12 months | 
| Number of Sanctions Imposed by the Court | Number of sanctions imposed by the court (e.g., brief stays in jail). This information will be collected from administrative records. | 12 months | 
| Number of Missed Court Appointments | Number of missed court appointments during the 12-month study period. This information will be collected from administrative records. | 12 months | 
| Vivitrol Participation | Number of Vivitrol injections from either arm of study. This information will be collected from administrative records. | 12 months | 
| Treatment Participation (Non-Vivitrol) | Number of oral naltrexone monthly prescriptions from either arm of study. This information will be collected from administrative records. | 12 months | 
| Change in Subjective Functioning: Medical Status | Subjective assessment of medical status using the Addiction Severity Index (ASI) Lite (a single measure with multiple domains) collected via interviews at baseline and approximately six months. | Baseline, 6 months | 
| Number of Participants Who Reported Improvement in Subjective Functioning: Employment/Support Status | Subjective assessment of employment opportunities collected via interviews at baseline and approximately six months. | Baseline, 6 months | 
| Number of Participants Who Reported Improvement in Substance Use | Subjective assessment of alcohol/drug use in past 30 days collected via interviews at baseline and approximately six months. | Baseline, 6 months | 
| Number of Participants Who Reported Illegal Behavior | Subjective assessment of illegal behavior using the question, Have you done anything that was against the law in the last 30 days? collected via interviews approximately six months after baseline. | approximately 6 months | 
| Number of Participants Who Reported Improvement in Subjective Functioning: Family/Social Relationships | Subjective assessment of family and social relationships using a single question about satisfaction with relationships over the past 30 days collected via interviews at baseline and approximately six months. | Baseline, approximately 6 months | 
| Change in Subjective Functioning: Psychiatric Status | Subjective assessment of psychiatric status using the Addiction Severity Index (ASI) Lite (a single measure with multiple domains) collected via interviews at baseline and approximately six months. | Baseline, approximately 6 months | 
| Treatment Satisfaction Score | Reported as average of 12-item treatment satisfaction score at approximately six months. A score of 5 indicates strong agreement with positive statements about treatment satisfaction; a score of 0 indicates strong disagreement. | Approximately 6 months | 
| Change in Medication-assisted Treatment (MAT) Attitudes | Change in MAT attitudes from baseline to follow-up. The average score of 4 questions about MAT for substance use disorder were calculated at baseline and follow-up, and the average score at baseline was subtracted from the average score at follow-up. The averages are based on questions for which a score of 5 indicates strong agreement with statements about MAT; a score of 1 indicates strong disagreement with such statements. | Baseline, approximately 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Court, Medication-assisted treatment, Pilot study, Opioid dependence, Criminal justice