Alcohol Reduction Among People With TB and HIV in India

Hiv Clinical Trial

— HATHI  

Official title:

Hybrid Trial for Alcohol Reduction Among People With TB and HIV in India (HATHI)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04230395
• Other study ID #: IRB00235134
• Secondary ID: R01AA027974
• Status: Recruiting
• Phase: N/A
• Start date: September 22, 2022
• Est. completion date: August 31, 2026

Study information

• Verified date: April 2024
• Source: Johns Hopkins University
• Contact: Amita Gupta
• Phone: 410-502-7696
• Email: agupta25[@]jhmi.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The highest incidence of tuberculosis disease (TB) in the world is in India, accounting for 27% of all new cases globally, with approximately 86,000 among persons with HIV (PWH). Unhealthy alcohol use can worsen the health of people who have Tuberculosis (TB) and people who have both TB and HIV. Behavioral interventions that 1) target alcohol use and 2) are integrated into TB and TB/HIV care may lead to better outcomes. The goal of this study is to test if a behavioral alcohol reduction intervention integrated into TB treatment can reduce alcohol use and improve TB and HIV health outcomes among people with unhealthy alcohol use. The aims of the HATHI study are: Aim 1: To test if a 4 session behavioral alcohol reduction intervention, called CAP (Counseling on Alcohol Problems), integrated into TB and TB/HIV Care can decrease unhealthy alcohol use among persons with TB and TB and HIV. Aim 2: To test if the CAP intervention, integrated into TB and TB/HIV care can improve TB and HIV clinical outcomes; Aim 3: To evaluate barriers and facilitators to integrating CAP into TB and TB/HIV care, and to determine the incremental costs of delivering CAP in TB and HIV clinical settings. Investigators hypothesize that CAP intervention will reduce alcohol use among persons with TB and TB with HIV, and that it delivery in the TB and TB/HIV setting will be acceptable to patient and providers and feasible.

Description:

In 2017, over 10 million people worldwide developed tuberculosis disease (TB), with 9% of cases among people with HIV (PWH). In that same year, there were 1.6 million deaths from TB, with 300,000 among PWH. The highest incidence of TB is in India, accounting for 27% of all new cases globally, with approximately 86,000 among PWH. Unhealthy alcohol use triples the risk of TB in the general population, increasing susceptibility to primary infection and reactivation. Among PWH, unhealthy alcohol use is associated with decreased use of and adherence to antiretroviral therapy (ART), lower viral suppression and increased mortality. Treatment for TB presents a unique opportunity to address unhealthy alcohol use among people with TB and HIV/TB given the frequent contact participants have with healthcare providers and the deleterious effects of unhealthy use on both HIV and TB clinical outcomes. Although combined cognitive behavioral therapy (CBT) and motivational enhancement therapy (MET) can be effective in reducing alcohol use, access to and implementation of such interventions is limited in high-need, under-resourced low and middle income (LMIC) settings. Even in settings where formal treatment is available, alcohol-related stigma and cost of treatment may prevent individuals from seeking care. Integrating treatment for unhealthy alcohol use into TB and HIV/TB care may overcome barriers to alcohol treatment for such individuals at risk for poor health outcomes. HATHI (Hybrid trial for Alcohol reduction among people with TB and HIV/TB in India), is a 2-arm hybrid type 1 effectiveness-implementation randomized controlled trial (RCT) examining the effectiveness of a four-session combined CBT/MET alcohol reduction intervention (CAP-Counseling on Alcohol Problems), followed by three intervention boosters, integrated into TB and HIV/TB care, compared with usual care (provider advice, referral to treatment as needed). There will be 3 phases. In Phase 1) investigators will tailor the intervention tailoring based on results from a) focus groups (FG) with patients with HIV/TB, medical and clinical staff, and the intervention counselors (IC) and b) individual intervention testing with a subgroup of HIV/TB patients. In Phase 2) investigators will conduct an RCT in which participants will be randomized to CAP intervention or to usual care. Investigators will stratify by HIV status to ensure balance of HIV between the groups. Effectiveness outcomes measured at 3, 6 and 12 months will include 1) self-reported alcohol use (primary) and phosphatidyl ethanol (PEth), an alcohol biomarker (secondary), and 2) TB and HIV clinical outcomes. In Phase 3, evaluating trial participants, counselors, clinical and organizational staff, investigators will use the RE-AIM implementation framework using mixed methods to assess barriers and facilitators to alcohol treatment integration in TB and HIV/TB clinical settings and to assess the incremental costs of this intervention strategy.

Setting: All phases of the study will take place at two sites in India: the Byramjee Jeejeebhoy Government Medical College (BJGMC) and Dr. DY Patil Medical College, Pune (DYPMC).

Objectives/Aims:

Aim 1: In a randomized controlled trial (RCT), to examine the effectiveness of CBT/MET integrated into TB and HIV/TB care compared to usual care on alcohol reduction.

Aim 2: In a RCT, to examine the effectiveness of CBT/MET integrated into TB and HIV/TB care compared to usual care on TB and HIV treatment outcomes.

Aim 3: Guided by the RE-AIM implementation framework, and using mixed methods, to 3a) evaluate patient, provider and organizational barriers and facilitators to integrated alcohol treatment in TB and HIV/TB settings, and 3b) measure incremental costs from health system and societal perspectives.

Prior to RCT implementation investigators will tailor CAP and make final modifications to the CAP manual. CAP will be enhanced with content specific to Pune such as local alcohol containing beverages and local or state drinking norms and alcohol impacts on TB and HIV progression and clinical outcomes. Investigators will modify the manual and test in focus groups.

Phase 2-Clinical Trial. This phase involves collection of routinely used research assessments for individuals with TB and HIV/TB at baseline, 3, 6, and 12 months and the launch of the RCT. The study will include adults individuals with newly diagnosed TB, unhealthy alcohol use, initiating TB medication treatment. Individuals will be recruited through both provider and self-referral. Up to half of the sample will have both TB and HIV. Eligible individuals will undergo baseline assessment which includes a medical history, clinical exam, questionnaires, and a blood spot for the alcohol biomarker PEth.

Assignments of Participants to the Study Intervention: Eligible participants will be randomized in a 1:1 ratio upon completion of the baseline evaluation. The study biostatistician, independent of the trial will generate the randomization sequence in permuted blocks and randomization will be stratified by the presence of HIV infection. A sealed envelope with study assignment will be used to conceal the study group assignment.

Study Conditions:

Control: Individuals in the control arm will receive standard of care TB and HIV treatment and usual care from participants' provider, which includes advice to reduce alcohol use and referral to alcohol treatment services at participants' provider's discretion. Participants will also receive a general guide on nutrition, diabetes, tobacco and alcohol.

Intervention: CAP is an up to 4-session manualized alcohol reduction treatment based on Cognitive Behavioral and Motivational Enhancement Therapy. Each session lasts up to 45 minutes. The 4 CAP sessions will be delivered by a counselor during an 8 week period, closely aligned to regular TB treatment follow up visits. After the 4 intervention sessions, individuals will receive 3 scripted booster sessions, one month apart, corresponding to participants' TB follow up visits.

Research Data Ascertainment: Assessments will occur at baseline (prior to randomization), 3 months (end of 4 session intervention), 6, and 12 months post-baseline. Data collection will include self-report questionnaires staff interviews, and biomarker and specimens and will encompass demographics, a clinical assessment, measurement of alcohol use, its severity and consequences; HIV measures including viral load, medication adherence and HIV retention in care; TB measures, including TB clearance, TB treatment default, TB medication adherence and TB retention in care. Other measures span mental health, tobacco and other substance use, quality of life, diabetes mellitus, motivation to change and self-efficacy.

Investigators' primary alcohol endpoint will occur at 6 months after baseline, with investigators' secondary endpoint at 12 months. Sample size calculations are based on data from behavioral alcohol reduction interventions in low and middle income countries.

Investigators' trial will enroll a total of 450 participants with TB or TB/HIV; The study will be conducted at two sites and 2 counselors at each site will administer the intervention. Power calculations assume a 10% loss to follow-up, and intra-class correlation coefficient of 0.04 (based on CAP/PREMIUM RCT) to account for 2 counselors per site, 2 sites). Analyses will also account for variation by counselor and by site.

Phase 3: The Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) implementation framework will be used to collect quantitative and qualitative assessments from 3 levels of stakeholders (Numbers approximate, pending thematic saturation). Investigators will evaluate barriers and facilitators to intervention reach, effectiveness, adoption, implementation and maintenance, focusing in implementation outcomes of feasibility, acceptability, appropriateness, fidelity and sustainability. Investigators will also calculate the incremental costs of the intervention.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 450
• Est. completion date: August 31, 2026
• Est. primary completion date: January 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Active TB defined as either a) microbiologically confirmed TB (sputum AFB smear positive by microscopy or +GeneXpert at entry) or b) clinical TB that is subsequently confirmed by Acid-Fast Bacilli (AFB) culture;

• with or without concurrent HIV infection)

• initiating TB therapy;

• age = 18 years of age;

• AUDIT Score = 8 in men /=4 in women.

Exclusion Criteria:

• already in treatment for unhealthy alcohol use;

• unable to participate in intervention sessions either due to severity of medical illness, cognitive dysfunction or active psychosis;

• pregnant (will refer directly to alcohol treatment);

• household member of current study participant;

Related Conditions & MeSH terms

• Hiv
• Tuberculosis

Intervention

Behavioral:
• CAP
4-session combination Motivational Enhancement Therapy and Cognitive Behavioral Therapy alcohol reduction intervention. The intervention will also include 3 booster sessions.

Other:
• Usual Care
Provider advice to reduce alcohol use per recommended standard of clinical care, and referral to treatment as indicated

Locations

Country	Name	City	State
India	BJ Government Medical College and Sassoon General Hospital	Pune	Maharashtra
India	Dr. D. Y. Patil Medical College	Pune	Maharashtra

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Phosphatidyl Ethanol	We will assess change in blood levels of Phosphatidyl Ethanol as an Alcohol Biomarker	3, 6, 12 months
Primary	Alcohol Use: Drinking days	Self reported number of drinking days on the 30-day Time Line Follow Back Interview (TLFB)	6 months
Primary	Alcohol Use: Heavy drinking days	Self reported heavy drinking days on the 30-day Time Line Follow Back Interview (TLFB)	6 months
Primary	Alcohol Use: Standard drinks per drinking day	Self reported standard drinks per drinking day the 30-day Time Line Follow Back Interview (TLFB)	6 months
Secondary	Change in Alcohol Use as assessed by change in Drinking days	Change in Self reported number of drinking days on the 30-day Time Line Follow Back Interview (TLFB)	3 months and 12 months
Secondary	Change in Alcohol Use as assessed by change in heavy Drinking days	Change in Self reported heavy drinking days on the 30-day Time Line Follow Back Interview (TLFB)	3 months and 12 months
Secondary	Change in Alcohol Use as assessed by change in standard drinks per drinking days	Change in Self reported standard drinks per drinking day on the 30-day Time Line Follow Back Interview	3 months and 12 months
Secondary	TB treatment failure, TB treatment default, or all-cause mortality	Composite outcome: TB treatment failure, TB treatment default, or all-cause mortality (defined as a binary outcome i.e. 0=none of these outcomes and 1= one or more of these outcomes)	12 months
Secondary	HIV-RNA Non-Suppression	This will be assessed as HIV-RNA >200 copies	6 months
Secondary	HIV-RNA Non-Suppression	This will be assessed as HIV-RNA >200 copies	12 months