Intestinal Microbiota Transplantation in Patients With Chronic Heart Failure

Chronic Heart Failure

Heart Failure, Intestinal Microbiota Transplantation, Heart Failure with Reduced Ejection Fraction, Heart Failure with Preserved Ejection Fraction

The purpose of this study is to determine whether people with CHF, who often have different gut bacteria from healthy, would benefit from replacing their gut bacteria with healthy donor bacteria (also known as Intestinal Microbiota Transplantation - IMT). IMT aims to restore healthy gut bacteria in patients with CHF, with previous studies showing its effectiveness, but further research is needed. IMT is an approved treatment for patients with infectious diarrhea. More than 10,000 IMTs are performed every year in the US. However IMT is not approved for patients with CHF, and thus considered investigational.

Hypothesis: CHF is thought to be partly mediated by inflammation. The primary hypotheses are anchored in the premise that the pathophysiology of CHF is in part driven by inflammation arising from low diversity, dysbiotic intestinal microbiota through at least three mechanisms including: i) enrichment of gram- negative lipopolysaccharide (LPS) producers; ii) enrichment of organisms with uremic toxin producing potential, particularly in the setting of impaired renal functional which is common in CHF; iii) depletion of short chain fatty acid producers (SCFA) which are known to be important anti-inflammatory molecules. The investigators hypothesize that IMT therapy will increase gut diversity, reduce inflammation and improve functional capacity and biomarkers of hemodynamic stress. Phase of Clinical Trial: 1 Study Design and Participants: Single-center, open-label study for safety and feasibility of IMT in patients with CHF. After consent, individuals of the ages 18+ with a diagnosis of CHF not due to acute myocarditis or infiltrative disease, will be enrolled to receive antibiotic preconditioning for 7 days followed by IMT daily for additional 7 days. Prior to antibiotics and IMT, recipients will be screened for inclusion/exclusion criteria, interviewed for medical history and medications, and consented. Additionally, prior to undergoing IMT and antibiotic preconditioning, baseline blood and fecal samples will be collected, and patients will undergo a six-minute walk test, echocardiogram, and quality of life questionnaire (emPHasis-10, a validated short questionnaire to assess health-related quality of life in those with CHF). Additional fecal sample would be collected following 7 days of antibiotics preconditioning and prior to initiation of active IMT therapy. Patients will undergo follow-up either by phone, video or in-person visit, or online survey of symptoms on days 1-21, and then monthly up to 6 months post-IMT to screen for serious adverse events (SAEs) and adverse events (AEs). Screening for SAEs and AEs will be done using a symptom questionnaire as well as by asking patients during our interview. Blood samples and a fecal sample will be collected from participants on months one and six post-IMT to assess circulating inflammatory mediators and to assess for changes in recipient microbiome (engraftment kinetics). At six months, patients will also undergo repeat six-minute walk test, echocardiogram, and quality of life questionnaire when logistically possible and clinically indicated.

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United States