Development of a Community-based HCV Treatment Completion Intervention Among HCV Positive Homeless Adults

Study Overview
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Brief Summary
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This randomized controlled trial (RCT) will test the efficacy of a Community Health Worker/Registered Nurse (CHW-RN) HCV intervention for homeless individuals, many who are also drug users. The intervention will be designed during Phase I of the proposal using an iterative process between a Community Advisory Board (CAB) and focus groups. The CHW/RN intervention will occur over a 2 or 3 month (8-12 weeks) period depending on the Direct-Acting Antiviral (DAA) prescribed. Homeless adults assigned to the CHW/RN HCV treatment group will receive culturally-sensitive education, case management, and daily DOT delivery of DAA by an RN-guided CHW. The CHW will run a brief (20 min) weekly 1:1 education and 20 min case management session over the 8 or 12 weeks and will deliver all components of the program (which will be developed and refined during Phase I). The CHW-RN HCV intervention will be compared to a clinic-based standard of care group (cbSOC). Primary outcomes are the completion of the Direct-Acting Agent (DAA) treatment (month 2 or 3) and SVR12 Cure (month 5 or 6). Secondary outcomes are improved mental health status, decrease in substance use, and improved access to health care, and shelter stability at month 5 or 6.

Detailed Description
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HCV infection disproportionately affects homeless and drug-using populations and represents a critical focus for effective HCV prevention at the individual and community level. Homeless persons have a 26 fold increase in HCV prevalence compared to the general population; particularly with injection drug use (IDU). In fact, 50-80% of HCV infection is among persons who inject drugs (PWID). Among homeless populations, risk factors for HCV include older age, IDU, needle sharing, previous incarceration, veteran status, fair-or-poor health status, and sharing toothbrushes. Among the 48% of HCV-infected homeless persons who did not inject drugs, correlates of HCV infection include older age, less education, use of drugs, and history of multiple tattoos. While HCV treatment for PWID can reduce HCV prevalence, despite recommended guidelines, only 1-6% of drug-using HCV-infected persons have received treatment. Among the homeless adults, factors associated with low HCV treatment completion include untreated mental illness, current substance use, unstable housing, and limited access to care. Although the new Direct Acting Agent (DAA) are costly, cure rates have risen to above 98%. Yet limited research has been conducted on DAA agents among drug-using homeless adults. Extending HCV treatment beyond the traditional tertiary care model and involving peer supports can facilitate access to HCV treatment. The scientific premise of this proposal is that homeless HCV positive adults often do not obtain/complete HCV treatment due to significant psychosocial barriers. Thus, developing and testing a strategy that combines treatment with psychosocial support would be expected to change this outcome. To our knowledge, no randomized controlled trial (RCT) has yet assessed the efficacy of a comprehensive community-based model that incorporates HCV and substance use treatment to address HCV among homeless persons, despite the critical need that exists. The proposed treatment concept - Community Health Worker/Registered Nurse (CHW-RN) - is innovative and helps HCV treatment reach beyond the clinic walls, directly into the community where the homeless reside, reducing barriers to treatment. Guided by our community-based model, the CHW/RN intervention will focus on improving social support, coping skills, problem-solving, self-management, physical and mental health, substance use, and stable housing. The proposed study will contribute to our knowledge about culturally-sensitive strategies for HCV treatment among homeless adults, many of whom use drugs and alcohol. It will address a substantial health disparity in a historically underserved population, with broader implications for public health. While DAAs have not been assessed among homeless adults using RCTs, homeless persons who are active drug users, in particular, have had challenges with uptake and compliance of other HCV treatments. To our knowledge, no study has evaluated the effect of a CHW/RN HCV treatment program, delivered in the community where the participant lives, compared to a cbSOC model to assess HCV treatment completion and Sustained Virologic Response (SVR) after 12 weeks of treatment completion. For further innovation, we will now evaluate the extent to which the pathways posed by the CHSCP and similar models, including the BMVP affect health outcomes by adding to Aim 3 analyses an examination of mechanisms of therapeutic change by the mediating effects of improved psychosocial and structural factors (e.g. housing, social support, etc ) on improved rates of SVR12. Improved understanding of the mechanisms of effect will advance the understanding of these factors and their role in determining health outcomes. The proposed study will pretest an RN-guided, CHW-delivered, program wherein a CHW/RN program will be developed and pretested with the community through focus group methodology. The intervention will focus on improving the completion of HCV treatment, reducing drug and alcohol use, reducing mental illness, and improving housing stability. The findings of this study can lay the groundwork for a subsequent larger trial to test the efficacy of the developed CHW/RN program more broadly and may inform health policy that could encourage enrollment of this high-risk group into HCV treatment. Results may also inform future cost-effective, community-based interventions that could be scaled-up and disseminated more broadly. Employing a treatment-as-prevention focus of HCV transmission in the community is urgent since HCV among the homeless represents a reservoir for HCV infection in the general population.

Official Title
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Development of a Community-based HCV Treatment Completion Intervention Among HCV Positive Homeless Adults

Conditions
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Hepatitis C Virus (HCV) Infection

Intervention / Treatment
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* Behavioral: Community health worker (CHW)/ registered nurse (RN) [CHW/RN]
* Behavioral: Clinic-based Standard of Care (cbSOC) Program (control group)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: currently homeless. A homeless person is defined as anyone who spent the previous night in a public or private shelter, a place not meant for sleeping (van, car, public facility, abandoned building) or in outdoor areas. age 18 or older; willing and able to provide informed consent; able to complete the screener; willing to have blood tests to be screened for HCV and tested HCV antibody positive; APRI ≤ 0.7, no signs of advanced cirrhosis (jaundice, ascites, encephalopathy) and willing to undergo the abdominal US as the standard of care (at the clinic). history of substance use (past 5 years). Exclusion Criteria: current ongoing treatment for HCV; current HBV infection; HIV infection and not receiving medications for HIV treatment; not speaking English or Spanish; and testing pregnant; and judged to be cognitively impaired

Ages Eligible for Study
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Minimum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Community Health Worker/Registered Nurse (CHW/RN)<br>Nurse-led Community Health Worker (CHW/RN) program delivered DOT for HCV treatment. | Behavioral: Community health worker (CHW)/ registered nurse (RN) [CHW/RN]<br>* A team of 2-3 CHWs and a research RN will deliver all components of the program including daily DOT delivery of Direct Acting Antiviral (DAA) and assess HCV side effects all under the guidance of their RN. Recruitment will be continuous: each CHW may be assigned up to 7-8 participants every 2-3 months until the target sample size (n=54 for the intervention group) is achieved. After the first dose of the DAA, the CHW will run a brief weekly 1:1 education and case management session over the 8 or 12 weeks (total 20 minutes). The CHW/RN team will assist the participant in picking up the monthly medication and storing the medication in a secure, locked cabinet at the research office. The CHW will rigorously track participants who have missed a dose, and will also be involved in facilitating medical, mental health, substance use, social service, legal appointments for participants, housing referrals, and accompany the participants to the appointments.<br>|
| Active Comparator: Clinic-based Standard of Care (cbSOC)<br>Standard of care for HCV treatment delivered by a clinic-based MD or clinic-based NP at the clinic site | Behavioral: Clinic-based Standard of Care (cbSOC) Program (control group)<br>* This program will be delivered by a clinic-based MD or clinic-based NP at the clinic site. Evaluation Staff (ES) will be hired and trained to do the interviewing/survey administration and follow-ups at the clinic-based site. The clinic NP will conduct, per usual care at the study clinics, the education and monitoring of these participants who will interact with the clinic-based-MD and/or NP monthly over the 8 or 12-week program. Usual care will include: 1) HCV pre-treatment education; 2) two month supply of DAA; 3) monitoring adverse events; and 4) responding to questions on HCV. Referral to drug/alcohol and housing programs will be provided over the standard of care. The cbSOC participants will not receive the community delivery of the DAA, or case management, or accompaniment to needed services. The cbSOC Program will receive the medication on a monthly basis from the clinic MD or NP.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Completion of HCV treatment | The completion of HCV treatment (7 days per week x 8 or 12-week treatment of DAA) will be measured by pill count to measure adherence in both groups. For the CHW/RN group, directly observed therapy will be utilized where the CHW or RN delivers the medication daily and documents it each time s/he observes the participant swallow a pill. For the cbSOC Program (control group), the clinic-based MD/NP will conduct a pill count monthly, based on the medications left in the pill bottle each month the participant is scheduled to pick up the next supply | 2-3 month | 
| SVR12 (sustained viral response at 12 weeks after treatment completion) | SVR12 Cure (HCV RNA < 25 IU/ml, detectable or undetectable) as tested at 5 or 6-month follow up (12 weeks after treatment completion) | 5-6 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug Use | Assessed by the drug items in the Texas Christian University (TCU) Screen V. Yes/No responses to substance dependency questions and the frequency of drug use based on a 5-point scale from 1 (never) to 5 (daily) will be assessed for each drug used. The total score ranges from 0 - 11; corresponding to the number of symptoms endorsed by the participant and the severity of SUD: mild disorder (2-3 points), moderate disorder (4-5 points), or severe disorder (6 or more points). | 2 or 3- and 5 or 6-month follow-up | 
| Alcohol Use | Assessed by a brief alcohol screening instrument The Alcohol Use Disorders Identification Test-Concise (AUDIT-C). AUDUT-C reliably identifies persons who are hazardous drinkers or have active alcohol use disorders (including alcohol abuse or dependence).The AUDIT-C has 3 questions and is scored on a scale of 0-12. Each AUDIT-C question has 5 answer choices valued from 0 points to 4 points. | 2 or 3- and 5 or 6-month follow-up | 
| Alcohol Use | Assessed by CAGE an internationally used assessment instrument for identifying alcoholics. Item responses on the CAGE are scored 0 or 1, with a higher score an indication of alcohol problems. A total score of 2 or greater is considered clinically significant. | 2 or 3- and 5 or 6-month follow-up | 
| Depression | Mental Health will be assessed by Patient Health Questionnaire-9 (PHQ-9). The PHQ-9 is a self-administered depression module of the Patient Health Questionnaire (PHQ). It contains 9 questions that help identify patients with clinically meaningful symptoms of depression. Patient responses are scored 0-3 with 0 representing not at all and 3 indicating nearly every day; thus, the PHQ-9 contains a total score range of 0-27. | 2 or 3- and 5 or 6-month follow-up | 
| Mental Health | Mental Health will be assessed by the Mental Health Inventory (MHI)-5; well-demonstrated reliability for detecting psychological disorders | 2 or 3- and 5 or 6-month follow-up | 
| Shelter Factors | Shelter Stability will be assessed by length of time residing in shelter vs elsewhere at 5 months | 5 or 6-month follow-up | 
| Health Care Access | Health Care Access will include number of healthcare visits made and purpose during the duration of the intervention | 2 or 3- and 5 or 6-month follow-up |