Tamara Y. Boney

Extended-Release Naltrexone to Prevent Opioid Relapse in Criminal Justice Offenders

BACKGROUND Extended-release naltrexone, a sustained-release monthly injectable formulation of the full mu-opioid receptor antagonist, is effective for the prevention of relapse to opioid dependence. Data supporting its effectiveness in U.S. criminal justice populations are limited. METHODS In this five-site, open-label, randomized trial, we compared a 24-week course of extended-release naltrexone (Vivitrol) with usual treatment, consisting of brief counseling and referrals for community treatment programs, for the prevention of opioid relapse among adult criminal justice offenders (i.e., persons involved in the U.S. criminal justice system) who had a history of opioid dependence and a preference for opioid-free rather than opioid maintenance treatments and who were abstinent from opioids at the time of randomization. The primary outcome was the time to an opioid-relapse event, which was defined as 10 or more days of opioid use in a 28-day period as assessed by self-report or by testing of urine samples obtained every 2 weeks; a positive or missing sample was computed as 5 days of opioid use. Post-treatment follow-up occurred at weeks 27, 52, and 78. RESULTS A total of 153 participants were assigned to extended-release naltrexone and 155 to usual treatment. During the 24-week treatment phase, participants assigned to extended-release naltrexone had a longer median time to relapse than did those assigned to usual treatment (10.5 vs. 5.0 weeks, P<0.001; hazard ratio, 0.49; 95% confidence interval [CI], 0.36 to 0.68), a lower rate of relapse (43% vs. 64% of participants, P<0.001; odds ratio, 0.43; 95% CI, 0.28 to 0.65), and a higher rate of opioid-negative urine samples (74% vs. 56%, P<0.001; odds ratio, 2.30; 95% CI, 1.48 to 3.54). At week 78 (approximately 1 year after the end of the treatment phase), rates of opioid-negative urine samples were equal (46% in each group, P=0.91). The rates of other prespecified secondary outcome measures--self-reported cocaine, alcohol, and intravenous drug use, unsafe sex, and reincarceration--were not significantly lower with extended-release naltrexone than with usual treatment. Over the total 78 weeks observed, there were no overdose events in the extended-release naltrexone group and seven in the usual-treatment group (P=0.02). CONCLUSIONS In this trial involving criminal justice offenders, extended-release naltrexone was associated with a rate of opioid relapse that was lower than that with usual treatment. Opioid-use prevention effects waned after treatment discontinuation. (Funded by the National Institute on Drug Abuse; ClinicalTrials.gov number, NCT00781898.).

A Multisite Pilot Study of Extended-Release Injectable Naltrexone Treatment for Previously Opioid-Dependent Parolees and Probationers

A feasibility study was conducted to pilot test the ability of 5 sites to recruit, treat, and retain opioid-dependent offenders in a trial of extended-release injectable naltrexone (XR-NTX). The participants, 61 previously opioid-dependent individuals under legal supervision in the community, received up to 6 monthly injections of Depotrex brand naltrexone and completed a 6-month follow-up interview. Six-month outcomes showed that those who completed treatment had significantly fewer opioid-positive urines and were less likely to have been incarcerated than those who had not completed treatment. The findings indicate that XR-NTX holds promise as a feasible, effective treatment option for opioid-dependent offenders.

Extended-release naltrexone to prevent relapse among opioid dependent, criminal justice system involved adults: Rationale and design of a randomized controlled effectiveness trial

BACKGROUND Extended-release naltrexone (XR-NTX, Vivitrol; Alkermes Inc.) is an injectable monthly sustained-release mu opioid receptor antagonist. XR-NTX is a potentially effective intervention for opioid use disorders and as relapse prevention among criminal justice system (CJS) populations. METHODS This 5-site open-label randomized controlled effectiveness trial examines whether XR-NTX reduces opioid relapse compared with treatment as usual (TAU) among community dwelling, non-incarcerated volunteers with current or recent CJS involvement. The XR-NTX arm receives 6 monthly XR-NTX injections at Medical Management visits; the TAU group receives referrals to available community treatment options. Assessments occur every 2 weeks during a 24-week treatment phase and at 12- and 18-month follow-ups. The primary outcome is a relapse event, defined as either self-report or urine toxicology evidence of ≥10 days of opioid use in a 28-day (4 week) period, with a positive or missing urine test counted as 5 days of opioid use. RESULTS We describe the rationale, specific aims, and design of the study. Alternative design considerations and extensive secondary aims and outcomes are discussed. CONCLUSIONS XR-NTX is a potentially important treatment and relapse prevention option among persons with opioid dependence and CJS involvement. ClinicalTrials.gov: NCT00781898.

Correlates of Trichomonas Prevalence Among Street-Recruited, Drug-Using Women Enrolled in a Randomized Trial

Objectives. Substance-using women need prevention technologies and programs to reduce risk of HIV/sexually transmitted infection (STI). We examined STI prevalence and identified risk correlates for female drug users. Methods. We used interviewer-administered and computer-assisted surveys, and tested specimens for four, treatable STIs (trichomonas, early syphilis, gonorrhea, chlamydia) on 198 HIV-seronegative, street-recruited, substance-using women enrolled in a randomized trial to reduce HIV/STI risk. Results. Most women were crack users (88%), reported sex exchange (80%) and were not in drug user treatment (74%). Two-thirds were African-American and nearly all were unemployed. Protection during sex was infrequent. African-American women reported fewer unprotected sex acts and fewer sexual partners, but greater crack use and more sex-for exchange, than whites or Hispanics. Trichomonas prevalence (36.9%) exceeded that for chlamydia (3.5%), syphilis (1.5%), and gonorrhea (0%). In multivariate logistic regression, having a primary and casual partner more than doubled (AOR 2.86) the risk of having trichomonas and being African-American raised the risk by more than 8 times (AOR 8.45). Conclusions. African-American, drug-using women, and women with multiple partner types, are in urgent need of effective STI/HIV prevention interventions.

Basic body knowledge in street-recruited, active drug-using women enrolled in a “body empowerment” intervention trial

Background: Drug-using women remain at high risk for HIV infection. Female condoms (FC) have proven potential and cervical barriers have promise to reduce HIV risk; their effective use may be boosted by familiarity and confidence about female anatomy. Women with high levels of crack cocaine use were assessed for their knowledge about reproductive anatomy, HIV/STI risk, as well as cancer screening behaviors. Methods: Women were recruited for a randomized trial of a behavioral intervention via mobile vans in Philadelphia known for high crack use and sex exchange. Knowledge and behavioral data on 198 women were collected via interviewer-administered questionnaire. Women were randomized into control (n=99) and intervention (n=99) arms. Five weekly, small-group, intervention sessions stressed “body empowerment” and teaching use of female-initiated barrier methods. Follow-up body knowledge data were collected at 12 months. Changes in and correlates of body knowledge were analyzed and compared. Results: Most participants were African-American (66%); their mean age was 39.6 years. At baseline, 44% of the sample erroneously believed women have sex and urinate from the same place; 62% erroneously believed that tampons could get lost in the abdominal cavity. Only 27% knew douching increased STI transmission risk; only 10% knew condoms reduce cervical cancer risk. At follow-up, overall body knowledge improved substantially, across both arms. Race was associated with high body knowledge at baseline but not at follow-up. Conclusions: Knowledge favoring use of women-initiated methods and cervical cancer prevention was very low in this hard-to-reach sample. Body knowledge improved substantially with enhanced voluntary counseling and testing (VCT) as well as the women-focused intervention. Body knowledge education must be targeted and tailored to drug-using women.

Relapse to opioid use disorder after inpatient treatment: Protective effect of injection naltrexone

BACKGROUND Opioid use disorder is often treated with short term hospitalization and medically supervised withdrawal from opioids followed by counseling alone without medication assisted treatment (MAT). More evidence is needed to confirm the expectation that the rate of relapse would be high after short term inpatient treatment and withdrawal from opioids without follow-up MAT. OBJECTIVE/METHODS To examine relapse to opioid use disorder in a randomized, multi-site effectiveness trial of extended-release injection naltrexone (XR-NTX) vs community-based treatment as usual (TAU) without medication, as a function of the type of clinical service where treatment was initiated-short-term inpatient (N=59), long-term inpatient (N=48), or outpatient (N=201). Inpatients typically were admitted to treatment actively using opioids and had completed withdrawal from opioids before study entry. Outpatients typically presented already abstinent for varying periods of time. RESULTS One month after randomization, relapse rates on TAU by setting were: short-term inpatient: 63%; long term inpatient: 14%; outpatient: 28%. On XR-NTX relapse rates after one month were low (<12%) across all three settings. At the end of the 6 month trial, relapse rates on TAU were high across all treatment-initiation settings (short term inpatient 77%; long term inpatient 59%; outpatient 61%), while XR-NTX exerted a modest protective effect against relapse across settings (short term inpatient: 59%; long term inpatient 46%; outpatient 38%). CONCLUSIONS Short term inpatient treatment is associated with a high rate of relapse among patients with opioid use disorder. These findings support the recommendation that medically supervised withdrawal from opioids should be followed by medication assisted treatment.

Assessing informed consent in an opioid relapse prevention study with adults under current or recent criminal justice supervision

Concerns persist that individuals with substance use disorders who are under community criminal justice supervision experience circumstances that might compromise their provision of valid, informed consent for research participation. These concerns include the possibilities that desire to obtain access to treatment might lead individuals to ignore important information about research participation, including information about risks, or that cognitive impairment associated with substance use might interfere with attending to important information. We report results from a consent quiz (CQ) administered in a multisite randomized clinical trial of long-acting naltrexone to prevent relapse to opioid use disorder among adults under community criminal justice supervision-a treatment option difficult to access by this population of individuals. Participants were required to answer all 11 items correctly before randomization. On average, participants answered 9.8 items correctly (89%) at baseline first attempt (n=306). At week 21 (n=212), participants scored 87% (9.5 items correct) without review. Performance was equivalent to, or better than, published results from other populations on a basic consent quiz instrument across multiple content domains. The consent quiz is an efficient method to screen for adequate knowledge of consent information as part of the informed consent process. Clinical researchers who are concerned about these issues should consider using a consent quiz with corrected feedback to enhance the informed consent process. Overall, while primarily useful as an educational tool, employing a CQ as part of the gateway to participation in research may be particularly important as the field continues to advance and tests novel experimental treatments with significant risks and uncertain potential for benefit.

Active Drug-Using Women Use Female-Initiated Barrier Methods to Reduce HIV/STI Risk: Results from a Randomized Trial

Background. We tested an original, woman-focused intervention, based on body empowerment, and female-initiated barrier methods, including the female condom (FC) and cervical barriers. Methods. Eligible women were >= 18 years of age, HIV seronegative, and active drug users, reporting 30% or greater unprotected sex acts. Both controls (C) and intervention (I) participants received enhanced HIV/STI harm reduction counseling. I participants underwent 5 additional weekly group sessions. We compared change in frequency of unprotected vaginal intercourse across arms at 12 months. Results. Among 198 enrolled women, over 95% completed followup. Two-thirds were African-American; most of them used crack, had a primary partner, and reported sex exchange. In paired t-tests from baseline to followup, the frequency of unprotected vaginal sex dropped significantly for I (primary P < 0.00, nonprimary P < 0.002) and C (primary P < 0.008, nonprimary P < 0.000) arms with all partners. The difference in change across arms was of borderline significance for primary partner (P = 0.075); no difference was seen for nonprimary partner (P = 0.8). Use of male condom and FC increased with both partner types over time, but more consistently among I women. Conclusion: The “value-added” impact of the intervention was observed mainly with primary partners. Body knowledge with routine FC counseling should be incorporated into interventions for drug-using women.

Personal Control Over Decisions to Participate in Research by Persons With Histories of Both Substance Use Disorders and Criminal Justice Supervision

Individuals must feel free to exert personal control over decisions regarding research participation. We present an examination of participants’ perceived personal control over, as well as reported pressures and threats from others, influencing their decision to join a study assessing the effectiveness of extended-release naltrexone in preventing opioid dependence relapse. Most participants endorsed a strong sense of control over the decision; few reported pressures or threats. Although few in number, participants’ brief narrative descriptions of the pressures and threats are illuminating and provide context for their perceptions of personal control. Based on this work, we propose a useful set of tools to help ascertain participants’ sense of personal control in joining research.