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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Heart Failure; Heart Failure With Preserved Ejection Fraction (HFPEF)
• Intervention / Treatment: Biological: Fecal Microbiota Transplantation (FMT) Capsules; Biological: Placebo capsules

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Chen Yang; Phone Number: 029-19959467156; Email: 19959467156@163.com

Study Locations

• China
  • Shanxi
    • Xi’an, Shanxi, China
      • The First Affiliated Hospital of Air Force Medical University
      • Contact: Chen Yang; Phone Number: 029-19959467156; Email: 19959467156@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1.Aged ≥ 60 years old;

• 2.Meeting the diagnostic criteria for HFpEF:

  1. Consistent with the epidemiological and demographic characteristics of HFpEF patients;
  2. Presence of clinical symptoms and/or signs of heart failure;
  3. Cardiac imaging examination indicating LVEF ≥ 50%;
  4. 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;

  5. Meet at least one of the following conditions:

     1. LVMI ≥ 115 g/m² (male) or ≥ 95 g/m² (female);
     2. LAVI > 34 ml/m²;
     3. Relative wall thickness > 0.42, or left ventricular free wall thickness > 12 mm;
     4. Septal e' < 7 cm/s, or lateral e' < 10 cm/s, or average E/e' ≥ 14;
     5. 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):

  1. Patients with severe intestinal barrier damage induced by various causes, such as sepsis, active massive gastrointestinal bleeding, intestinal perforation;
  2. Patients diagnosed with fulminant colitis or toxic megacolon;
  3. 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;
  4. Patients with congenital or acquired immunodeficiency diseases;
  5. 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;
  6. 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.

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
Placebo Comparator: Placebo Control Group	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.
Experimental: Fecal Microbiota Transplantation (FMT) Group	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score from Baseline to Week 20	The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a validated patient-reported outcome measure assessing heart failure-specific quality of life. The change in the overall summary score from baseline to week 20 will be compared between the FMT group and the placebo group. Higher scores indicate better health status.	Baseline, Week 4, Week 20

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in NYHA Functional Class from Baseline to Week 20	New York Heart Association (NYHA) functional classification is used to assess the severity of heart failure symptoms. Changes in NYHA class from baseline to week 20 will be compared between groups.	Baseline, Week 4, Week 20
Change in 6-Minute Walk Test (6MWT) Distance from Baseline to Week 20	The 6-minute walk test is a measure of functional capacity in patients with heart failure. The distance walked in 6 minutes will be assessed at baseline, week 4, and week 20 to evaluate changes in exercise tolerance.	Baseline, Week 4, Week 20
Change in Serum N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) Level from Baseline to Week 20	Serum NT-proBNP is a key biomarker for heart failure severity. Levels will be measured at baseline, week 4, and week 20 to assess changes in cardiac strain.	Baseline, Week 4, Week 20
Change in Minnesota Living with Heart Failure Questionnaire (MLHFQ) Total Score from Baseline to Week 20	The MLHFQ is a patient-reported questionnaire evaluating the impact of heart failure on quality of life. Higher scores indicate greater impairment. Changes from baseline to week 20 will be compared.	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	Serum levels of the following inflammatory and endothelial activation markers (all units: pg/mL) will be measured to assess the effect of FMT on systemic inflammation in patients with HFpEF: NLRP3, IL-1β, TNF-α, IL-6, MCP-1, ICAM-1, and VCAM-1. Each biomarker will be analyzed separately for changes from baseline.	Baseline, Week 4, Week 20
Change in Gut Microbiota Composition and Diversity from Baseline to Week 20	Fecal samples will be collected for 16S rRNA sequencing to analyze changes in gut microbiota composition, diversity, and taxonomic profiles following FMT intervention.	Baseline, Week 20
Change in Serum Nitric Oxide (NO) Level from Baseline to Week 20	Serum nitric oxide (NO) concentration will be measured as an indicator of vascular endothelial function.	Baseline, Week 4, Week 20
Change in Frailty Status Using the Fried Frailty Phenotype Criteria from Baseline to Week 20	Frailty status will be assessed using the Fried criteria to evaluate changes in physical vulnerability.	Baseline, Week 20
Change in Nutritional Status Using the Mini Nutritional Assessment (MNA) Scale from Baseline to Week 20	Nutritional status will be evaluated using the Mini Nutritional Assessment (MNA) scale. Changes in total score from baseline to week 20 will be compared.	Baseline, Week 20
Change in Basic Activities of Daily Living (BADL) Scale Score from Baseline to Week 20	The Basic Activities of Daily Living (BADL) scale will be used to assess changes in patients' functional independence in daily activities.	Baseline, Week 20
Change in SARC-F Scale Score from Baseline to Week 20	The SARC-F questionnaire is a validated tool for sarcopenia screening, assessing strength, assistance with walking, rising from a chair, climbing stairs, and falls. Changes in total score from baseline to week 20 will be evaluated.	Baseline, Week 20
Change in Fecal Short-Chain Fatty Acids (SCFAs) from Baseline to Week 20	Concentrations of fecal short-chain fatty acids (including acetate, propionate, and butyrate) will be quantified (unit: μmol/g) to assess changes in gut microbial fermentation.	Baseline, Week 20
Change in Serum Trimethylamine N-Oxide (TMAO) from Baseline to Week 20	Serum TMAO level will be measured (unit: μM) as a marker of gut microbiota-dependent metabolism of dietary phosphatidylcholine and carnitine.	Baseline, Week 20
Change in Serum Bile Acids Profile from Baseline to Week 20	Serum concentrations of primary and secondary bile acids (e.g., cholic acid, deoxycholic acid) will be quantified (unit: μM) to evaluate changes in bile acid metabolism.	Baseline, Week 20
Change in Serum Indole-3-Propionate (IPA) from Baseline to Week 20	Serum IPA level will be measured (unit: μM) as a gut microbiota-derived tryptophan metabolite.	Baseline, Week 20
Change in Serum Indoxyl Sulfate from Baseline to Week 20	Serum indoxyl sulfate level will be quantified (unit: μM) as a representative gut microbiota-derived uremic toxin.	Baseline, Week 20
Change in White Blood Cell (WBC) Count from Baseline to Week 20	WBC count will be measured (unit: ×10⁹/L) to monitor changes in systemic inflammatory/immune status.	Baseline, Week 4, Week 20
Change in Hemoglobin (HGB) Concentration from Baseline to Week 20	Hemoglobin concentration will be measured (unit: g/L) to assess changes in oxygen-carrying capacity.	Baseline, Week 4, Week 20
Change in Platelet (PLT) Count from Baseline to Week 20	Platelet count will be measured (unit: ×10⁹/L) to evaluate changes in hemostatic/thrombotic potential.	Baseline, Week 4, Week 20
Change in Serum Creatinine from Baseline to Week 20	Serum creatinine level will be measured (unit: μmol/L) to assess renal function.	Baseline, Week 4, Week 20
Change in Estimated Glomerular Filtration Rate (eGFR) from Baseline to Week 20	eGFR will be calculated (unit: mL/min/1.73m²) as a marker of renal function.	Baseline, Week 4, Week 20
Change in Alanine Aminotransferase (ALT) from Baseline to Week 20	Serum ALT level will be measured (unit: U/L) to assess hepatocellular integrity.	Baseline, Week 4, Week 20
Change in Aspartate Aminotransferase (AST) from Baseline to Week 20	Serum AST level will be measured (unit: U/L) to assess hepatocellular integrity.	Baseline, Week 4, Week 20
Change in Fasting Blood Glucose from Baseline to Week 20	Fasting blood glucose concentration will be measured (unit: mmol/L) to assess glycemic status.	Baseline, Week 4, Week 20
Change in Serum Electrolytes (Sodium, Potassium, Chloride) from Baseline to Week 20	Serum concentrations of sodium (Na⁺), potassium (K⁺), and chloride (Cl-) will be measured (all units: mmol/L). Each electrolyte will be analyzed separately for changes from baseline.	Baseline, Week 4, Week 20
Change in Left Atrial Volume Index (LAVI) from Baseline to Week 20	LAVI (unit: mL/m²) will be measured to assess changes in left atrial remodeling.	Baseline, Week 4, Week 20
Change in Left Ventricular Mass Index (LVMI) from Baseline to Week 20	LVMI (unit: g/m²) will be measured to assess changes in left ventricular hypertrophy.	Baseline, Week 4, Week 20
Change in Pulmonary Artery Systolic Pressure (PASP) from Baseline to Week 20	PASP (unit: mmHg) will be measured to assess changes in pulmonary artery pressure.	Baseline, Week 4, Week 20
Change in E/e' Ratio from Baseline to Week 20	The E/e' ratio (unitless) will be measured to assess changes in left ventricular filling pressure.	Baseline, Week 4, Week 20
Change in Serum Diamine Oxidase (DAO) from Baseline to Week 20	Serum DAO level (unit: U/L) will be measured to assess changes in intestinal barrier integrity.	Baseline, Week 4, Week 20
Change in Serum D-Lactate from Baseline to Week 20	Serum D-lactate level (unit: μmol/L) will be measured to assess changes in intestinal permeability.	Baseline, Week 4, Week 20
Change in Serum Endotoxin from Baseline to Week 20	Serum endotoxin level (unit: EU/mL) will be measured to assess changes in bacterial translocation and intestinal barrier function.	Baseline, Week 4, Week 20
Change in Total Body Fat Mass from Baseline to Week 20	Body fat mass will be measured (unit: kg) to assess changes in adiposity.	Baseline, Week 20

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Air Force Medicial University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: May 24, 2026
• First Submitted That Met QC Criteria: June 1, 2026
• First Posted (Actual): June 5, 2026

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Fecal Microbiota Transplantation; FMT; Heart Failure with Preserved Ejection Fraction; HFpEF
• Additional Relevant MeSH Terms: Pharmaceutical Preparations; Therapeutics; Dosage Forms; Biological Therapy; Fecal Microbiota Transplantation; Capsules
• Other Study ID Numbers: KY20252186-F-1

Drug and device information, study documents

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