Harm Reduction With Pharmacotherapy (HaRP) (HaRP)

Harm Reduction With Pharmacotherapy for Homeless Adults With Alcohol Dependence

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.

Study Overview

• Status: Completed
• Conditions: Alcohol Use Disorder
• Intervention / Treatment: Other: Placebo; Behavioral: HRC; Drug: XR-NTX

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 308
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington - Harborview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Assessment-only; Assessment-only control condition
Active Comparator: HRC; 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
Experimental: XR-NTX+HRC; 3 doses of active medication (380 mg injection/month) + Harm reduction counseling at one-month intervals over three months.	Behavioral: HRC; Drug: XR-NTX
Placebo Comparator: Placebo+HRC; 3 doses of placebo + harm reduction counseling at one-month intervals over a three-month period	Other: Placebo; Behavioral: HRC

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events Due to the Study Medication	The Systematic Assessment for Treatment Emergent Effects (SAFTEE) interview,68,69 which was tailored for use with this medication, includes open-ended, categorical and Likert-scale questions assessing symptoms that correspond to potential adverse events associated with XR-NTX. This measure will be embedded in the CRF and will be used to establish tolerability of the study medication. For these descriptive scores, we took the average count of adverse events reported at each time point during the study. This was a total summary score ranging from 0 to 20, where a higher score represents a higher number of adverse events experienced.	baseline, week 4, week 8, week 12, week 24, week 36

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA); Alkermes, Inc.
• Investigators: Principal Investigator: Susan E Collins, PhD, University of Washington

Publications and helpful links

General Publications

• Collins SE, Saxon AJ, Duncan MH, Smart BF, Merrill JO, Malone DK, Jackson TR, Clifasefi SL, Joesch J, Ries RK. Harm reduction with pharmacotherapy for homeless people with alcohol dependence: protocol for a randomized controlled trial. Contemp Clin Trials. 2014 Jul;38(2):221-34. doi: 10.1016/j.cct.2014.05.008. Epub 2014 May 17.
• Collins SE, Duncan MH, Saxon AJ, Taylor EM, Mayberry N, Merrill JO, Hoffmann GE, Clifasefi SL, Ries RK. Combining behavioral harm-reduction treatment and extended-release naltrexone for people experiencing homelessness and alcohol use disorder in the USA: a randomised clinical trial. Lancet Psychiatry. 2021 Apr;8(4):287-300. doi: 10.1016/S2215-0366(20)30489-2. Epub 2021 Mar 10.
• Fentress TSP, Wald S, Brah A, Leemon G, Reyes R, Alkhamees F, Kramer M, Taylor EM, Wildhood M, Frohe T, Duncan MH, Clifasefi SL, Collins SE. Dual study describing patient-driven harm reduction goal-setting among people experiencing homelessness and alcohol use disorder. Exp Clin Psychopharmacol. 2021 Jun;29(3):261-271. doi: 10.1037/pha0000470.
• Goldstein SC, Spillane NS, Tate MC, Nelson LA, Collins SE. Measurement invariance and other psychometric properties of the Short Inventory of Problems (SIP-2R) across racial groups in adults experiencing homelessness and alcohol use disorder. Psychol Addict Behav. 2023 Mar;37(2):199-208. doi: 10.1037/adb0000833. Epub 2022 May 5.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2013
• Primary Completion (Actual): October 11, 2018
• Study Completion (Actual): June 30, 2019

Study Registration Dates

• First Submitted: August 22, 2013
• First Submitted That Met QC Criteria: August 27, 2013
• First Posted (Estimate): August 30, 2013

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: May 5, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: harm reduction, naltrexone, alcohol use disorder, homelessness
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Alcohol Drinking; Alcoholism
• Other Study ID Numbers: 45134; 1R01AA022309-01 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No