Harm Reduction With Pharmacotherapy (HaRP)

Study Overview
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Brief Summary
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The goal of this study is to test the efficacy of extended-release naltrexone and harm reduction counseling in reducing alcohol-related harm among homeless people with alcohol dependence.

Detailed Description
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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.

Official Title
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Harm Reduction With Pharmacotherapy for Homeless Adults With Alcohol Dependence

Conditions
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Alcohol Use Disorder

Intervention / Treatment
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* Drug: XR-NTX
* Other: Placebo
* Behavioral: HRC


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Assessment-only<br>Assessment-only control condition | |
| Active Comparator: HRC<br>Harm reduction counseling, which entails provision of feedback and support of harm reduction goals and safer drinking provided at one-month intervals over a 3-month period. | Behavioral: HRC<br> <br> |
| Experimental: XR-NTX+HRC<br>3 doses of active medication (380 mg injection/month) + Harm reduction counseling at one-month intervals over three months. | Drug: XR-NTX<br> <br> Behavioral: HRC<br> <br> |
| Placebo Comparator: Placebo+HRC<br>3 doses of placebo + harm reduction counseling at one-month intervals over a three-month period | Other: Placebo<br> <br> Behavioral: HRC<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alcohol Quantity | Using the Alcohol Quantity and Use Assessment, we will collect data on peak alcohol quantity. | Baseline, week 4, week 8, week 12, week 24, week 36 | 
| Alcohol-related Harm | Using the Short Inventory of Problems, we collected data on alcohol-related harm in the past month. The range of possible scores on the single summary score is 0-45, and higher scores indicate a greater experience of alcohol-related harm. | Baseline, week 4, week 8, week 12, week 24, week 36 | 
| Alcohol Frequency | Addiction Severity Index (ASI - 5th edition) will be used to assess frequency of alcohol use in the past 30 days. | baseline, week 0, week 4, week 8, week 12, week 24, week 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Motivation to Change Ruler | Motivation to change will be measured using the 10-point motivation ruler, where the stem was How motivated are you to make changes in your drinking to reduce harm? and 1= not at all motivated and 10=totally motivated. Thus, higher scores correspond to higher motivation for alcohol harm reduction | baseline, week 4, week 8, week 12, week 24, week 36 | 
| Alcohol Craving | Alcohol craving will be measured using the psychometrically valid, 5-item, 6-point Likert-scale Penn Alcohol Craving Scale (PACS). The score ranges from 0-30, with higher scores representing a higher level of craving. | baseline, week 4, week 8, week 12, week 24, week 36 | 
| Publicly Funded Service Utilization Costs | Administrative data on publicly funded service utilization will be obtained from the King County Correctional Facility, King County Medic One/Emergency Medical Services, Harborview Medical Center (HMC), and the Washington State Comprehensive Hospital Abstract Reporting System (CHARS) for the 2-year pre-study period through the 24-week follow-up. We will obtain participant consent and HIPAA authorizations for these data at the information session. We will collect the following data: a) number of Medic One/EMS dispatches and associated costs; b) number of ER visits and associated costs; c) number of inpatient hospital admissions and total costs per admission (CHARS and HMC); d) number of bookings, length of stay and daily cost for the King County Correctional Facility. These data will be used to create overall cost outcomes. | 2yr pretest, 12-week treatment period, 24-week follow-up period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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harm reduction, naltrexone, alcohol use disorder, homelessness