Clinical trial NCT05288790: Microbiome Metabolites and Alcohol in HIV to Reduce CVD RCT
Official title: Microbiome Metabolites and Alcohol in HIV to Reduce CVD RCT
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Microtia
Dysbiosis
Alcohol Drinking
HIV Infections
Cardiovascular Diseases
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: University of Louisville
name: Boston University
First posted: 2022-03-21
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a two-arm randomized double blind clinical trial study design.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: Inclusion Criteria:

* HIV infected

Exclusion Criteria:

* Not fluent in English

Primary outcomes:
measure: Firmicutes to Bacteroidetes ratio
timeFrame: 6 months
Secondary outcomes:
measure: Intestinal permeability
timeFrame: 6, 12 months
measure: Firmicutes to Bacteroidetes ratio
timeFrame: 12 months
measure: Microbial Translocation
timeFrame: 6, 12 months
measure: Inflammation
timeFrame: 6, 12 months
Other outcomes:
measure: Mortality
timeFrame: 6 and 12 months
measure: CVD risk
timeFrame: 6 and 12 months
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
References: