Gut Microbiome Profiling in Patients With Chronic Heart Failure

• Conditions: Nonischemic Cardiomyopathy; Heart Failure With Reduced Ejection Fraction

• Registration Number: NCT06361524
• Lead Sponsor: Stanford University

Brief Summary

The goal of this observational study is to learn about the composition and function of the gut microbiome in adults with chronic heart failure with reduced ejection fraction. The main questions the study aims to answer are:

1. How does the gut microbiome and its interactions with the host change over time in adults with chronic heart failure?

2. How do these changes relate to heart failure disease severity and complications?

Detailed Description

During this study, investigators will recruit adults diagnosed with chronic heart failure with reduced ejection fraction caused by non-ischemic cardiomyopathy. These individuals will undergo longitudinal profiling. This will include detailed profiling of their (1) gut microbiome, (2) blood metabolic and immune markers, and (3) heart failure clinical status. Integrated results will lead to deeper understanding of how gut microbiome interacts with and affects the host in chronic heart failure.

Study Timeline

• Study Start: 2018-08-01
• Study First Submitted: 2024-04-05
• Study First Submitted QC: 2024-04-10
• Study First Posted: 2024-04-12
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-13
• Last Update Posted: 2025-05-16
• Primary Completion: 2028-12
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

• Heart failure with reduced ejection fraction (left ventricular ejection fraction less than 50%)
• Non-ischemic cardiomyopathy
• Body mass index (BMI) 18-40 kg/m2

Exclusion Criteria

• Treated diabetes
• Advanced kidney disease
• Cirrhosis
• Significant gastrointestinal disease including any history of inflammatory bowel disease
• History of extensive bowel resection
• Active malignancy or systemic chemotherapy within the past 12 months
• Active infection
• Current or recent (within 4 weeks) use of systemic antibiotics, commercial probiotics, immunosuppressive or immunomodulatory medications
• Pregnancy/lactation

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Temporal changes in the gut microbiome community composition in chronic heart failure	12 months from baseline visit	Longitudinal changes in the gut microbiome composition and functionality in chronic heart failure will be determined. Microbiome signatures will be mapped from fecal samples collected every 3 months over a 12 month period, generated from shotgun metagenomic sequencing data and after processing through bioinformatic pipelines.
Advanced heart failure-associated microbiome signatures	24 months from baseline visit	A map of gut microbiome compositional and functional features associated with a composite clinical outcome of advanced heart failure (composite of needing heart transplantation (including active listing), left ventricular assist device implantation, transition to hospice, or death) that occurs within 24 months of baseline visit. Fecal samples will be collected every 3 months over the first 12 month period. Microbiota composition will be determined by shotgun metagenomic sequencing, with taxonomic and metabolic pathway signatures generated using bioinformatic pipelines, respectively. Comprehensive microbiome signatures will encompass alpha and beta diversity, and differential abundance analysis.

Secondary Outcome Measures

Name	Time	Method
Comprehensive longitudinal metabolome profile in chronic heart failure	12 months from baseline visit	Changes in the host (human) metabolome profile in chronic heart failure with reduced ejection fraction will be determined. Participants provide fasting blood samples every 3 months for 12 months, from which plasma samples are prepared. Plasma metabolites are run through liquid chromatography-mass spectrometry (LC-MS) columns. MetID (Metabolite Identification from a reference database) and our LC-MS data are used to identify hundreds of metabolites with confidence levels 1-2. Many of the identified metabolites are gut microbiome-derived.
Longitudinal change in the self-reported functional status	12 months from baseline visit	Participant self-reported functional status will be assessed via Kansas City Cardiomyopathy Questionnaire-12, which participant will complete at each study visit (every 3 months for 12 months). Overall summary and clinical summary scores (each 0-100, with 0 corresponding to severe and 100 corresponding to no functional limitations) will be calculated and compared over visits.
Comprehensive longitudinal cytokine profile in chronic heart failure	12 months from baseline visit	Changes in the host (human) cytokines in chronic heart failure with reduced ejection fraction will be determined. Participants provide fasting blood samples every 3 months for 12 months, from which serum samples are prepared. Cytokines are profiled using a 76-cytokine Luminex profiling system at the Stanford Human Immune Monitoring Center. This involves attaching antibodies specific to cytokines to beads using a capture molecule. The fluorescent molecules are attached to the cytokines, and fluorescence is used as the measure of cytokine abundance.
Longitudinal change in New York Heart Association (NYHA) functional class	12 months from baseline visit	Participants' functional status (as measured by NYHA class, which ranges from 1 to 4, with 1 being no to minimal symptoms with activity, and 4 being symptoms at rest) will be assessed at each study visit for the first 12 months (every 3 months).

Trial Locations

Locations (1)

Stanford University; 🇺🇸 Stanford, California, United States