Harm Reduction With Pharmacotherapy (HaRP)

Homelessness and alcohol dependence are commonly co-occurring and serious public health
issues. Unfortunately, abstinence-based alcohol treatment approaches are minimally effective
in engaging and successfully treating homeless individuals with alcohol dependence. There
have therefore been calls for more flexible and client-centered approaches tailored to this
population's needs. Innovative, low-barrier approaches (e.g., Housing First and alcohol
management programs) have been applied with this population and are efficacious in reducing
alcohol use and related problems as well as utilization of publicly funded services and
associated costs. Such approaches have been referred to as harm-reduction interventions
because they focus on reducing alcohol-related harm for affected individuals and their
communities without requiring a commitment to abstinence-based goals. Although psychosocial,
harm-reduction approaches are beginning to proliferate for this population, there are few
pharmacological counterparts to support and enhance these efforts. One medication that could
address this treatment gap is extended-release naltrexone (XR-NTX; marketed as Vivitrol®).
XR-NTX is a 30-day, extended release formulation of the opioid receptor antagonist,
naltrexone, and is administered monthly via gluteal intramuscular injection. The proposed
Phase II study features a four-arm RCT (N=300) designed to test the efficacy of XR-NTX as a
pharmacological adjunct to existing psychosocial harm-reduction services provided by
community agencies to homeless people with alcohol dependence. The proposed study will
include a 24-week follow-up and will test the relative efficacy of 3 active treatment
combinations—1) XR-NTX+harm reduction counseling, 2) placebo+harm reduction counseling and 3)
harm reduction counseling only (HRC)—compared to the services as usual (TAU) that all
participants receive from community agencies. This proposed design will allow us to dismantle
active treatment components and thereby detect potential "placebo effects" of both the
administration of an injection and attention from a medical professional. In this study,
there are three primary specific aims. First, we will test the relative efficacy of XR-NTX,
placebo and HRC compared to TAU in decreasing alcohol quantity, frequency and alcohol-related
problems. Second, we will test hypothesized mediators of the intervention effects.
Specifically, we hypothesize that the active treatments will precipitate increases in
motivation to change and decreases in craving, which, in turn, will mediate the active
treatment effects on alcohol outcomes. Finally, we will test treatment effects on publicly
funded service costs (i.e., emergency medical services, ER visits, hospital admissions, and
county jail). It is hypothesized that XR-NTX, placebo and HRC groups will show greater
decreases in publicly funded service costs than the TAU group.

Inclusion Criteria:

- being a registered client at one of the named partnering sites

- being at least 21 years of age (for legal reasons)

- agreeing to use an adequate form of birth control (if female and in childbearing
years) fulfilling criteria for current alcohol dependence according to DSM-IV-TR
criteria as determined by the SCID-I/P

Exclusion Criteria:

- refusal or inability to consent to participation in research

- constituting a risk to safety and security of other clients or staff

- known sensitivity or allergy to naltrexone/XR-NTX

- current treatment with naltrexone/XR-NTX

- being pregnant or nursing

- suicide attempts within the past year

- renal insufficiency/serum creatinine level > 1.5

- current opioid dependence according to the DSM-IV-TR criteria

- liver transaminases (AST, ALT) > 5 times the upper limit of normal (ULN)

- clinical diagnosis of decompensated liver disease