Microbiome Metabolites and Alcohol in HIV to Reduce CVD RCT (META HIV CVD)

Among people living with HIV, heavy drinking increases the risk of heart disease and death. Studies suggest that alcohol changes the number and kind of bacteria in your gut and these changes increase the risk of heart disease and death. This randomized controlled trial will determine whether a pill containing healthy gut bacteria can increase the number good bacteria in the gut, lower levels of inflammation, and lower the risk of heart disease and death.

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Diseases; HIV Infections; Alcohol Drinking; Dysbiosis; Microtia
• Intervention / Treatment: Dietary supplement: Probiotic; Dietary supplement: Placebo

Detailed Description

Among people living with HIV (PLWH), heavy drinking increases the risk of cardiovascular disease (CVD) and death. Data suggest that alcohol-associated gut dysbiosis partially drives this risk. Whether interventions targeting alcohol-associated gut dysbiosis among PLWH improve dysbiosis, lower levels of microbial translocation, inflammation, and harmful metabolites (e.g., trimethylamine N-oxide [TMAO)]) is unknown. The investigators' hypothesis for this P01 application is that among PLWH, a probiotic can mitigate or reduce alcohol associated gut dysbiosis and lower levels of microbial translocation, inflammation, and improve metabolite profiles (Project 1); and that harmful levels of these metabolites will be associated with higher CVD and death risk (Project 2). This team, with expertise in alcohol, HIV, gut microbiome, and biomarker research has conducted two NIAAA funded trials, a metabolite study, and a gut microbiome study among Russian PLWH who are heavy drinkers. Data from these studies show that among PLWH: (1) heavy drinking is associated with incident CVD, death and gut dysbiosis (characterized by a reduction in butyrate producing bacteria); and (2) this gut dysbiosis is associated with inflammation, altered bile acids, and high TMAO levels. Given these data and reports from pilot studies showing that probiotics are safe, may improve gut dysbiosis and reduce inflammation among PLWH, the investigators propose an RCT among 250 PLWH with heavy alcohol consumption who are on antiretroviral therapy and have CD4+ counts≥350 cells/mm3 to compare the effects of a probiotic tailored to alcohol associated gut dysbiosis vs. placebo to: (1) improve GI dysbiosis; (2) reduce plasma metabolite (e.g., TMAO) and biomarker levels of microbial translocation and inflammation; and (3) lower CVD and mortality risk. All participants will receive evidenced-based counseling for alcohol use. The specific aims will compare the effects of a tailored probiotic vs. placebo at 6 months on (Aim 1) dysbiosis (fecal Firmicutes to Bacteroidetes (F/B) ratio, primary study outcome; fecal Lachnospiraceae-family of butyrate producers) and plasma metabolites (plasma butyrate, deoxycholic acid:cholic acid ratio, and TMAO) (Aim 2) biomarkers of inflammation plasma, IL-6, D-dimer, sCD14), microbial translocation [Lipopolysaccharide binding protein], (Aim 3) cardiovascular risk (Reynolds risk score), mortality risk (VACS index); (Aim 4 exploratory) alcohol consumption (% heavy drinking days in past month) and HIV disease progression (CD4 cell count). The investigators hypothesize that as compared with placebo, the probiotic arm will have significantly: (1) higher F/B ratio and levels of fecal Lachnospiraceae, plasma butyrate, deoxycholic acid: cholic acid ratio and lower levels of TMAO; (2) lower plasma biomarker levels of microbial translocation and inflammation; (3) lower Reynolds risk score and VACS index; (4) lower % heavy drinking days in the past month and higher CD4 cell counts. The findings from this RCT, Microbiome, mETabolites, and Alcohol in HIV to reduce CVD (META HIV CVD RCT), will inform probiotics' role as standard adjunctive therapy complementing alcohol interventions among PLWH who are heavy drinkers.

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Grace Wallace, BS; Phone Number: 615-936-5356; Email: grace.wallace@vumc.org
• Study Contact Backup: Name: Emily Smith, MPH; Phone Number: 6158757253; Email: emily.k.smith@vumc.org

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University Medical Center
      • Contact: David Crenshaw, MSW; Phone Number: 615-322-7343

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• HIV infected

Exclusion Criteria:

• Not fluent in English

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study Supplement; Probiotic	Dietary supplement: Probiotic; Dietary supplement
Placebo Comparator: Study placebo; Placebo	Dietary supplement: Placebo; Placebo sachet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Firmicutes to Bacteroidetes ratio	Dysbiosis	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intestinal permeability	measuring levels of butyrate, deoxycholic acid:cholic acid ratio, and TMAO	6, 12 months
Firmicutes to Bacteroidetes ratio	Dysbiosis measurement	12 months
Microbial Translocation	measuring plasma lipopolysaccharide binding protein	6, 12 months
Inflammation	measuring plasma for interleukin 6 [IL-6], D-dimer, and sCD14	6, 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Veterans Aging Cohort Study Index Score (lower scores are better and higher scores are worse) (ranges from 0-164)	6 and 12 months
CVD risk	Reynolds Risk Score (the higher the score the higher the risk) (ranges from 100-400 mg/dL)	6 and 12 months

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: Boston University; University of Louisville

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2023
• Primary Completion (Estimated): August 28, 2026
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: February 28, 2022
• First Submitted That Met QC Criteria: March 10, 2022
• First Posted (Actual): March 21, 2022

Study Record Updates

• Last Update Posted (Actual): June 24, 2025
• Last Update Submitted That Met QC Criteria: June 18, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Drinking Behavior; Congenital Abnormalities; Otorhinolaryngologic Diseases; Ear Diseases; Alcohol Drinking; Cardiovascular Diseases; Dysbiosis; Congenital Microtia
• Other Study ID Numbers: P01AA029542 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No