Extended-Release Naltrexone Opioid Treatment at Jail Re-Entry
Condition: Heroin Dependence; Opioid-Related Disorders
MeSH terms: Opioid-Related Disorders; Heroin Dependence
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to compare the effectiveness of extended-release naltrexone
      (XR-NTX) vs. enhanced treatment-as-usual (TAU) among opioid dependent adults leaving NYC
      jails. In parallel, we propose to recruit a matched, quasi-experimental methadone cohort,
      which will result in a naturalistic comparison of XR-NTX vs. an established jail-based
      methadone treatment program standard-of-care. Our primary aim is to compare time-to-relapse
      among participants treated with XR-NTX vs. randomized TAU controls and time-to-relapse among
      XR-NTX arm vs. jail-based MTP participants, following release from jail. Secondary aims will
      compare related opioid treatment outcomes post-release across all arms.
    

Detailed description: 
      This study is a randomized control trial of XR-NTX (n=85) vs. enhanced TAU (n=85) among
      opioid dependent adults leaving NYC jails who explicitly reject agonist treatment. Initiating
      treatment the week prior to release and continuing for 24 weeks post-release, we hypothesize
      the XR-NTX arm will demonstrate significantly longer time-to-relapse vs. TAU. In parallel, we
      propose to recruit a matched, quasi-experimental methadone cohort (n=85), which will result
      in a naturalistic comparison of XR-NTX vs. an established jail-based MTP standard-of-care.

      Rationale: Immediate relapse to drug, alcohol, and tobacco use is a nearly universal and
      expected near-term outcome among adults with addiction disorders leaving U.S. jails. Yet
      while opioid agonist therapies are proven and effective re-entry interventions, many US
      correctional facilities, including almost all large U.S. municipal jails, do not offer these
      treatments. However, in New York City (NYC), jail-to-community methadone treatment is, since
      1986, a well-studied standard-of-care, yet many inmates eligible to initiate the methadone
      treatment program (MTP) while incarcerated do not, possibly due to anti-methadone patient
      preferences. Rather, the vast majority of these jail detainees undergo a brief 6-day
      methadone taper following arrest, remain in jail for brief periods out-of-treatment while
      'drug free' and undergoing a decline in physiologic opioid tolerance, nearly universally
      relapse to heroin or other illicit opioid use following release, and are re-arrested in the
      next 12 months at rates of 50-75%. Extended-release naltrexone (XR-NTX, Vivitrol), now
      FDA-approved for opioid dependence, produces a 30-day mu opioid receptor antagonist blockade,
      and offers an potentially promising modality for 'inoculating' persons leaving jails against
      immediate opioid relapse. Persons injected with 380mg of XR-NTX are unable to effectively
      experience euphoria or respiratory depression when returning to average doses of illicit
      opioids for the ensuing 4-5 weeks. An injection prior to release would possibly give the
      individual a month or so to return home from jail, experience opioid abstinence, and then
      either continue XR-NTX, initiate agonist or behavioral treatments, or, resume a significantly
      postponed relapse to illicit use. Our team recently established the feasibility of
      administering XR-NTX to opioid dependent adults within a week of release in NYC jails. We now
      propose to conduct a large, definitive randomized controlled trial estimating the
      effectiveness of XR-NTX as opioid treatment at release from jail vs. a counseling- and
      referral-enhanced treatment-as-usual (TAU) condition. We also propose to recruit a
      non-randomized, quasi-experimental cohort of participants in a jail-based methadone
      maintenance program (MTP), allowing an additional comparison of XR-NTX to a methadone
      standard-of-care.

      Specific Aim 1: Randomized Effectiveness Trial of XR-NTX vs. TAU for Jail-to-Community
      Re-Entry Opioid Relapse Prevention. Our primary aim is to compare time-to-relapse among
      participants treated with XR-NTX vs. randomized TAU controls, following release from jail.

      Specific Aim 2: Quasi-Experimental Comparison of XR-NTX vs. a Methadone Treatment Program for
      Re-Entry Opioid Relapse Prevention. To compare time-to-relapse among the XR-NTX RCT arm vs.
      jail-based MTP participants using a quasi-experimental design.

      Specific Aim 3a-e: Related Opioid Treatment Outcomes. To compare re-entry rates of 5
      treatment outcomes across all arms: 3a) community treatment initiation and retention, 3b) any
      opioid and other illicit drug or alcohol use, defined as continuous counts of both days,
      amount/day, and urine toxicologies, 3c) injection drug use and HIV sexual risk factors, 3d)
      accidental drug overdose and mortality, and, 3e) rates of re-incarceration and an exploratory
      analysis of cost-effectiveness.

      Implications: While there is growing interest in the newly approve use of XR-NTX for opioid
      treatment, its effectiveness has not been evaluated in any correctional facilities, including
      large municipal jails, vs. usual care, nor in the context of standard-of-care methadone
      treatment. This study will allow providers, correctional and public health authorities,
      including our collaborators at the NYC Department of Health and Mental Hygiene, and payers
      and policy makers to assess the utility of XR-NTX as re-entry opioid treatment, with
      important implications for limiting the great public safety and societal costs of heroin and
      prescription opioid addictions. Further, NYC jail inmates are predominantly African American
      and Hispanic, and represent communities disproportionately affected by unemployment, family
      poverty, HIV and hepatitis C, all downstream effects of opioid dependence. As the majority of
      opioid addicted persons leave jail return to their neighborhoods untreated and prone to rapid
      relapse, we hypothesize adding XR-NTX to the re-entry 'toolbox' will save both money and
      lives in these under-served communities.

      This study is part of the NIDA "Studies of Medication for Addiction Treatment in Correctional
      Settings (SOMATICS)" U01 Collaborative. Our distinct NIH-funded study at NYU has been aligned
      with two other jail-based opioid treatment studies conducted by researchers at Friends
      Research Institute (FRI) in Baltimore, MD, and at UCLA. SOMATICS seeks to harmonize
      assessments and interventions across the three research centers (RCs) and the three
      independent studies in order to leverage power, sample size, and increase the
      generalizability of findings. Each of the RCs in the SOMATICS cooperative will conduct their
      own individual trial, sharing one study arm with another RC, and several core assessments
      across all sites. The SOMATICS collaborative will have a common Statistical Analysis Plan and
      DSMP including a single DSMB. The collaborative primary and secondary outcomes across all
      sites are listed below:

      Collaborative Primary Outcome Measures:

      1. DSM-5 Opioid Use Disorder Diagnosis during the 30 days prior to the 6 months post-release
      follow-up assessment: Measured by: DSM-5 checklist via a modified CIDI-2 Substance Abuse
      Module.

      Collaborative Secondary Outcome Measures:

        1. Illicit Opioid use: measured by urine drug testing results at 6 months post-release

        2. Number of days incarcerated: Measured by self-report during the 6 months post-release.

        3. HIV risk behavior: Measured by self-report (Drug Risk Assessment Battery [RAB] Needle
           Use score) at the 6-month post-release follow-up assessment.

        4. Number of days of Opioids, Cocaine, Alcohol, Benzodiazepines, and/or IV Drug Use:
           Measured by Time Line Follow Back at 6 months post-release follow-up (TLFB; NYU, UCLA)
           and ASI (FRI).

        5. Non-opioid drug use (Cocaine, Amphetamines, and Benzodiazepines): measured by urine drug
           testing at 6 months post-release

        6. Number of days in any drug abuse treatment: Measured by self-report at 6 months
           post-release.

        7. Number of arrests: Measured by self-report data collected at 6 months post-release.

        8. Craving scores (for NYU and UCLA sites only): Measured by self-report craving scale at 6
           months post-release.

        9. Non-lethal overdose (Yes/No): Measured by self-report during the 6 months post-release.

       10. Lethal overdose (Yes/No): Measured by public records data reviewed at 6 months
           post-release.

       11. WHO Quality of Life-BREF (WHOQOL-BREF) score: Measured by self-report at 6 months
           post-release.

       12. Analyses of above same secondary outcomes at 12 months follow-up.

       13. Analyses of above same secondary outcomes at 24 months follow-up.
    

Intervention name(s): Extended-Release Naltrexone
Intervention type(s): Drug
Intervention description(s): Extended-Release Naltrexone (Vivitrol®), 380mg administered 1x/month by intramuscular injection.
Other intervention name(s): Vivitrol; XR-NTX
Intervention MeSH terms: Naltrexone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Heroin Dependence; Opioid-Related Disorders