Extended-Release Naltrexone Opioid Treatment at Jail Re-Entry

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.

Due to the nature of this study, which includes both randomized arms (XR-NTX and enhanced
TAU) as well as a non-randomized observational arm (methadone treatment group, MTP) there
are separate Inclusion/Exclusion criteria for those randomized vs. Non-Randomized, detailed
below.

Randomized Arms (XR-NTX, ETAU)

Inclusion Criteria:

1. Adults >18yo incarcerated in NYC jails with known release dates.

2. DSM-V criteria for current opioid use disorder (DSM-IV opioid dependence).

3. Not currently in or planning to pursue agonist (methadone, buprenorphine) treatment at
release.

4. Currently opioid free by history ('detoxed') and with a negative urine for all
opioids.

5. General good health as determined by medical evaluation.

Exclusion Criteria:

1. Pregnancy, lactation, or planning conception.

2. Active medical illness (i.e., severe liver disease, congestive heart failure)
precluding safe participation.

3. Untreated or poorly controlled psychiatric disorder precluding safe participation.

4. History of allergic reaction to naltrexone.

5. Current chronic pain condition treated with opioids.

Non-Randomized Arm (MTP) Inclusion Criteria

1. Adults >18yo incarcerated in NYC jails with known release dates.

2. DSM-V criteria for current opioid use disorder (DSM-IV opioid dependence).

3. Currently receiving regular methadone maintenance treatment through KEEP.

4. General good health as determined by medical evaluation.

Exclusion Criteria

1. Pregnancy, lactation, or planning conception.

2. Active medical illness (i.e., severe liver disease, congestive heart failure)
precluding safe participation.

3. Untreated or poorly controlled psychiatric disorder precluding safe participation.

4. In community methadone treatment program at the time of most recent arrest.