Fecal Microbiota Transplantation for Elderly Patients With HFpEF: A Randomized Controlled Trial

Official title

Fecal Microbiota Transplantation for Elderly Patients With Heart Failure With Preserved Ejection Fraction: A Randomized Controlled Trial

Overview

This is a single-center, randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy and safety of fecal microbiota transplantation (FMT) in elderly patients with heart failure with preserved ejection fraction (HFpEF). HFpEF is a common type of heart failure in older adults, often associated with poor quality of life and frequent hospitalizations. Recent research suggests that changes in gut bacteria may contribute to the progression of HFpEF. FMT aims to restore a healthy gut microbiome, which may improve heart function and reduce symptoms. Participants will be randomly assigned to receive either FMT or a placebo treatment. The primary goal is to compare changes in the Kansas City Cardiomyopathy Questionnaire (KCCQ) score between the two groups at 20 weeks. Secondary goals include assessing improvements in exercise capacity (6-minute walk test), NYHA functional class, and safety outcomes. The study will enroll 50 elderly patients (aged ≥60 years) with confirmed HFpEF. All participants will receive standard medical care for HFpEF throughout the study. This trial is sponsored by The First Affiliated Hospital of Air Force Medical University and conducted in accordance with ethical standards.

Interventions

• Biological Fecal Microbiota Transplantation (FMT) Capsules
  Bowel preparation with polyethylene glycol (PEG) before treatment, followed by oral administration of fecal microbiota transplantation (FMT) capsules. Patients will receive standard HFpEF medical care throughout the study.
• Biological Placebo capsules
  Bowel preparation with polyethylene glycol (PEG) before treatment, followed by oral administration of identical-appearing placebo capsules. Patients will receive standard HFpEF medical care throughout the study.

Primary outcome measures

• Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score from Baseline to Week 20 [Time frame: Baseline, Week 4, Week 20]

Secondary outcome measures (12)

• Change in NYHA Functional Class from Baseline to Week 20 [Time frame: Baseline, Week 4, Week 20]
• Change in 6-Minute Walk Test (6MWT) Distance from Baseline to Week 20 [Time frame: Baseline, Week 4, Week 20]
• Change in Serum N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) Level from Baseline to Week 20 [Time frame: Baseline, Week 4, Week 20]
• Change in Minnesota Living with Heart Failure Questionnaire (MLHFQ) Total Score from Baseline to Week 20 [Time frame: Baseline, Week 4, Week 20]
• Change in Serum Inflammatory Biomarkers (NLRP3, IL-1β, TNF-α, IL-6, MCP-1, ICAM-1, VCAM-1) from Baseline to Week 20 [Time frame: Baseline, Week 4, Week 20]
• Change in Gut Microbiota Composition and Diversity from Baseline to Week 20 [Time frame: Baseline, Week 20]
• Change in Serum Nitric Oxide (NO) Level from Baseline to Week 20 [Time frame: Baseline, Week 4, Week 20]
• Change in Frailty Status Using the Fried Frailty Phenotype Criteria from Baseline to Week 20 [Time frame: Baseline, Week 20]
• Change in Nutritional Status Using the Mini Nutritional Assessment (MNA) Scale from Baseline to Week 20 [Time frame: Baseline, Week 20]
• Change in Basic Activities of Daily Living (BADL) Scale Score from Baseline to Week 20 [Time frame: Baseline, Week 20]
• Change in SARC-F Scale Score from Baseline to Week 20 [Time frame: Baseline, Week 20]
• Change in Fecal Short-Chain Fatty Acids (SCFAs) from Baseline to Week 20 [Time frame: Baseline, Week 20]

Eligibility criteria

Inclusion criteria

• 1.Aged ≥ 60 years old;
• 2.Meeting the diagnostic criteria for HFpEF:

• Consistent with the epidemiological and demographic characteristics of HFpEF patients;
• Presence of clinical symptoms and/or signs of heart failure;
• Cardiac imaging examination indicating LVEF ≥ 50%;
• In sinus rhythm: BNP ≥ 35 pg/ml and/or NT-proBNP ≥ 125 pg/ml;In atrial fibrillation: BNP ≥ 105 pg/ml and/or NT-proBNP ≥ 365 pg/ml;
• Meet at least one of the following conditions:

• LVMI ≥ 115 g/m² (male) or ≥ 95 g/m² (female);
• LAVI > 34 ml/m²;
• Relative wall thickness > 0.42, or left ventricular free wall thickness > 12 mm;
• Septal e' < 7 cm/s, or lateral e' < 10 cm/s, or average E/e' ≥ 14;
• Tricuspid regurgitation velocity > 2.8 m/s, or pulmonary artery systolic pressure > 35 mmHg;
• 3.NYHA functional class Ⅱ-Ⅲ;
• 4.Complicated with metabolic diseases such as hypertension, diabetes and obesity;
• 5.Accompanied by gastrointestinal symptoms;
• 6.Well-tolerated to current anti-heart failure regimens with stable medication for at least 1 month;
• 7.Stable heart failure condition without acute exacerbation;
• 8.Basically normal cognitive function, capable of understanding scale assessment contents;
• 9.Able to perform daily activities independently;
• 10.Fully understanding the purpose of this clinical trial, voluntary participation and signing of written informed consent.

Exclusion criteria

• 1.Symptoms caused by non-cardiac diseases;
• 2.Patients with any contraindication to Fecal Microbiota Transplantation (FMT):

• Patients with severe intestinal barrier damage induced by various causes, such as sepsis, active massive gastrointestinal bleeding, intestinal perforation;
• Patients diagnosed with fulminant colitis or toxic megacolon;
• Patients unable to tolerate enteral nutrition meeting 50% of calorie requirements due to severe diarrhea, significant fibrous intestinal stenosis, severe gastrointestinal hemorrhage, high-output intestinal fistula and other conditions;
• Patients with congenital or acquired immunodeficiency diseases;
• Patients receiving high-risk immunosuppressive or cytotoxic drugs recently, such as rituximab, doxorubicin, or moderate-to-high dose steroids (prednisone ≥ 20 mg/d) administered continuously for more than 4 weeks;
• Severely immunosuppressed patients with neutrophil count < 1500/mm³;
• 3.History of myocardial infarction, coronary artery bypass grafting, or any event that may reduce LVEF within 6 months before enrollment (unless LVEF ≥ 50% was confirmed);
• 4.Received valve replacement surgery within 6 months before enrollment;
• 5.Poorly controlled blood pressure (SBP ≥ 180 mmHg or DBP ≥ 100 mmHg);
• 6.Current acute decompensated heart failure requiring intervention;
• 7.Resting heart rate > 120 beats per minute, or complicated with malignant arrhythmia;
• 8.Significant coronary artery disease requiring PCI revascularization;
• 9.Severe renal insufficiency (serum creatinine > 442 μmol/L) or patients on dialysis;
• 10.Pre-existing gastrointestinal diseases, including ulcerative colitis, Crohn's disease, irritable bowel syndrome, chronic diarrhea;
• 11.Current malignant tumors requiring anti-tumor treatment;
• 12.Complicated with acute diseases or acute exacerbation of chronic diseases at present;
• 13.Participation in other interventional clinical trials or oral intake of probiotic preparations within the past 3 months.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital of Air Force Medical University — Xi’an

Identifiers

NCT: NCT07628777 · KY20252186-F-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗