Randomized Double-blind Controlled Clinical Study of SGLT-2i Combined With Probiotic Preparations in Elderly Patients With HFpEF

HFpEF has a high incidence and lacks effective therapy, and its onset is closely related to systemic inflammation and intestinal dysbacteriosis.SGLT-2i exerts its effects by diuresis, anti-inflammatory and improving energy metabolism, whereas probiotics modulate intestinal flora, reduce inflammatory markers, and regulate immune responses.The combination of the two drugs is not only expected to exert synergistic therapeutic potential, but may also reduce the risk of sarcopenia associated with SGLT-2i weight loss.This study aims to combine henagliflozin and a probiotic preparation on the basis of standard anti-heart-failure therapy, and to observe their effects on cardiac and renal function, intestinal barrier function, quality of life, and exercise tolerance in elderly patients with HFpEF, while exploring the underlying mechanisms, so as to provide new data and therapeutic strategies for the treatment of elderly HFpEF patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure, Preserved Ejection Fraction
• Intervention / Treatment: Drug: Henggliflozin Combined with Probiotics; Drug: Henggliflozin; Drug: double placebo

• Study Type: Interventional
• Enrollment (Estimated): 162
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: JiChenyang; Phone Number: +86 15591423352; Email: 3260126173@qq.com

Study Locations

• China
  • Shanxi
    • Xi’an, Shanxi, China
      • The First Affiliated Hospital of Air Force Medical University
      • Contact: The First Affiliated Hospital of Air Force Medical University; Phone Number: +86 15591423352; Email: 3260126173@qq.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1. Age over 60 years; 2.Relevant investigations within 6 months meet diagnostic criteria for HFpEF:

  1. epidemiologic and population characteristics of patients with HFpEF;
  2. presence of symptoms and/or signs of heart failure;
  3. Cardiac imaging suggests LVEF >=50%;
  4. BNP>=35pg/ml and (or) NT-pro BNP>=125pg/ml in sinus rhythm, and BNP>=105pg/ml and (or) NT-pro BNP>=365pg/ml in atrial fibrillation;
  5. at least one of the following conditions is met: 1) LVMI>=115 g/m^2(male)or 95 g/m^2(female); 2) LAVI>34 ml/m^2; 3) Relative wall thickness>0.42;or left ventricular free wall thickness>12mm; 4) E/e'>=14; 5) Ventricular septal e'<7cm/s, or lateral wall e'<10cm/s, or mean e'<8cm/s; 6) Tricuspid regurgitant velocity>2.8m/s, or pulmonary artery systolic pressure>35mmHg; 3.NYHA class II to III for cardiac function; 4. not taking SGLT-2 inhibitors within 6 months before enrollment; 5. no probiotic preparations taken within 3 months before enrollment; 6. The current anti-HF Therapeutic Regimen is well tolerated by patients and is stable for at least 1 month; 7. Currently stable HF with no acute exacerbations; 8. Cognitive Functioning is basically normal with comprehensible assessment scale content; 9. possess basic behavioral ability, being able to perform daily activities independently or with the help of accessory aids; 10. Understand the purpose of the Clinical Study, voluntarily participate and sign informed consent.

Exclusion Criteria:

• 1. the patient's symptoms are due to noncardiac disease; 2. In those with contraindications to Henggliflozin:

  1. those who are allergic to henggliflozin;
  2. severe renal impairment (eGFR<30ml/min/1.73m^2), end-stage renal disease, or those requiring dialysis; 3. In those with contraindications to probiotics:
  1. Patients with severe impairment of the intestinal barrier associated with sepsis, active massive bleeding from the digestive tract, perforation, and other causes.
  2. those with current diagnosis of fulminant colitis or toxic megacolon.
  3. Enteral feeding that cannot tolerate 50% caloric requirement due to severe diarrhea, significant fibrous intestinal stenosis, severe gastrointestinal bleeding, high-flow intestinal fistula, etc.
  4. Patients with congenital or acquired immune deficiency.
  5. Those recently treated with high-risk immunosuppression or cytotoxic drugs: e.g., continued use of rituximab, doxorubicin, or a medium-to high-dose steroid hormone (20 mg/d prednisone or higher) for more than 4 weeks.
  6. Severe immunosuppression: Neutrophils <1 500/mm^3. 4. had a myocardial infarction within 6 months before enrollment, had a coronary artery bypass graft procedure, or had any event that could reduce LVEF (unless an LVEF >=50%) confirmed; 5. valve replacement surgery within 6 months before enrollment; 6.Poor blood pressure control (SBP>=180mmHg or DBP>=100 mmHg); 7. Current acute decompensated heart failure requires treatment; 8. Resting heart rate exceeding 120 beats/min, or complicated by malignant Arrhythmia; 9. Significant coronary artery lesions require PCI revascularization; 10. Severe renal insufficiency (blood creatinine, Cr >442μmol/L) or receiving dialysis treatment; 11. Patients with urinary tract infection at entry; symptoms and signs of urinary tract infection, such as urinary tract irritation signs (frequent urination, painful urination, urgency), pain and tenderness above the pubic bone, fever, pain or percussion pain in the waist, etc., and urine bacterial culture colony counts >=105/ml; 12. currently having a malignancy that requires treatment; 13. Current concurrent acute disease or acute exacerbation of chronic disease; 14.Participated in other interventional investigators within 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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Henggliflozin Combined with Probiotics Group	Drug: Henggliflozin Combined with Probiotics; Primary anti-HF therapy + Henagliflozin Proline Tablets (10mg, 1 times/day) + clostridial enterococcus triple live tablet (400mg, 3 times/day) orally, for 12 weeks.
Experimental: Henggliflozin Monotherapy Group	Drug: Henggliflozin; Primary anti-HF therapy + Henagliflozin Proline Tablets (10mg, 1 times/day) + placebo (400mg, 3 times/day) orally, for 12 weeks.
Placebo Comparator: double placebo group	Drug: double placebo; Primary anti-HF therapy +Two types of placebo tablets orally, for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kansas City Cardiomyopathy Questionnaire (KCCQ)scale score	The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a validated patient-reported outcome measure used to assess heart failure-specific quality of life. The change in the overall summary score from baseline to Week 12 will be compared between the groups. Higher scores indicate better health status.	Baseline, Week 4, Week 8,Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NYHA functional classification	The 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 12 will be compared between groups.	Baseline, Week 4, Week 8,Week 12
6-Minute Walk Test (6MWT) Distance	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, Week 8,and Week 12 to evaluate changes in exercise tolerance.	Baseline, Week 4, Week 8, Week 12
Serum N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) Level	Serum NT-proBNP is a key biomarker for heart failure severity. Levels will be measured at baseline, Week 4, Week 8, and Week 12 to assess changes in cardiac strain.	Baseline, Week 4, Week 8,Week 12
Minnesota Living with Heart Failure Questionnaire (MLHFQ) Total Score	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 12 will be compared.	Baseline, Week 4, Week 8,Week 12
Serum Inflammatory Biomarkers (NLRP3, IL-1β, TNF-α, IL-6, MCP-1, ICAM-1, VCAM-1)	Serum levels of the following inflammatory and endothelial activation markers will be measured to assess the effect of drugs 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 8, Week 12
Gut Microbiota Composition and Diversity	Fecal samples will be collected for 16S rRNA sequencing to analyze changes in gut microbiota composition, diversity, and taxonomic profiles following drugs intervention.	Baseline, Week 4, Week 8, Week 12
Frailty Status Using the Fried Frailty Phenotype Criteria	Frailty status will be assessed using the Fried criteria to evaluate changes in physical vulnerability.	Baseline, Week 4, Week 8, Week 12
Nutritional Status Using the Mini Nutritional Assessment (MNA) Scale	Nutritional status will be evaluated using the Mini Nutritional Assessment (MNA) scale. Changes in total score from baseline to Week 12 will be compared.	Baseline, Week 4, Week 8, Week 12
Basic Activities of Daily Living (BADL) Scale Score	The BADL scale will be used to assess changes in patients' functional independence in daily activities.	Baseline, Week 4, Week 8, Week 12
SARC-F Scale Score	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 12 will be evaluated.	Baseline, Week 4, Week 8, Week 12
Fecal Short Chain Fatty Acids (SCFAs)	Concentrations of fecal short-chain fatty acids, including acetate, propionate, and butyrate, will be quantified to assess changes in gut microbial fermentation.	Baseline, Week 12
Serum Trimethylamine-N Oxide (TMAO)	Serum TMAO levels will be measured as a marker of gut microbiota-dependent metabolism of dietary phosphatidylcholine and carnitine.	Baseline, Week 12
Serum Bile Acids Profile	Concentrations of primary and secondary bile acids, such as cholic acid and deoxycholic acid, will be quantified to evaluate changes in bile acid metabolism.	Baseline, Week 12
White Blood Cell (WBC) Count	WBC count will be measured to monitor changes in systemic inflammatory/immune status.	Baseline, Week 12
Hemoglobin (HGB) Concentration	Hemoglobin concentration will be measured to assess changes in oxygen-carrying capacity.	Baseline, Week 12
Platelet (PLT) Count	Platelet count will be measured to evaluate changes in hemostatic/thrombotic potential.	Baseline, Week 12
Serum Creatinine	Serum creatinine level will be measured to assess renal function.	Baseline, Week 12
Estimated Glomerular Filtration Rate (eGFR)	eGFR will be calculated as a marker of renal function.	Baseline, Week 12
Alanine Aminotransferase (ALT)	Serum ALT level will be measured to assess hepatocellular integrity.	Baseline, Week 12
Aspartate Aminotransferase (AST)	Serum AST level will be measured to assess hepatocellular integrity.	Baseline, Week 12
Fasting Blood Glucose	Fasting blood glucose concentration will be measured to assess glycemic status.	Baseline, Week 12
Serum Electrolytes (Sodium, Potassium, Chloride)	Serum concentrations of sodium, potassium, and chloride will be measured. Each electrolyte will be analyzed separately for changes from baseline.	Baseline, Week 12
Left Atrial Volume Index (LAVI)	LAVI will be measured to assess changes in left atrial remodeling.	Baseline, Week 12
Left Ventricular Mass Index (LVMI)	LVMI will be measured to assess changes in left ventricular hypertrophy.	Baseline, Week 12
Pulmonary Artery Systolic Pressure (PASP)	PASP will be measured to assess changes in pulmonary artery pressure.	Baseline, Week 12
E/e' Ratio	The E/e' ratio will be measured to assess changes in left ventricular filling pressure.	Baseline, Week 12
Total Body Fat Mass	Body fat mass will be measured to assess changes in adiposity.	Baseline, Week 12

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: June 30, 2026
• First Submitted That Met QC Criteria: June 30, 2026
• First Posted (Actual): July 7, 2026

Study Record Updates

• Last Update Posted (Actual): July 7, 2026
• Last Update Submitted That Met QC Criteria: June 30, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Probiotics; heart failure with preserved ejection fraction，HFpEF; Henggliflozin
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure; Heart Failure, Diastolic; Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Probiotics
• Other Study ID Numbers: KY20262160

Drug and device information, study documents

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