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

Phase 2Not Yet RecruitingNCT07687212

The First Affiliated Hospital of Air Force Medicial University162 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

162

Conditions

Heart Failure, Preserved Ejection Fraction

Interventions

Eligibility

Sex: ALLMin age: 60 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: Baseline, Week 4, Week 8,Week 12

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline, Week 12

White Blood Cell (WBC) Count

WBC count will be measured to monitor changes in systemic inflammatory/immune status.

Time frame: Baseline, Week 12

Hemoglobin (HGB) Concentration

Hemoglobin concentration will be measured to assess changes in oxygen-carrying capacity.

Time frame: Baseline, Week 12

Platelet (PLT) Count

Platelet count will be measured to evaluate changes in hemostatic/thrombotic potential.

Time frame: Baseline, Week 12

Serum Creatinine

Serum creatinine level will be measured to assess renal function.

Time frame: Baseline, Week 12

Estimated Glomerular Filtration Rate (eGFR)

eGFR will be calculated as a marker of renal function.

Time frame: Baseline, Week 12

Alanine Aminotransferase (ALT)

Serum ALT level will be measured to assess hepatocellular integrity.

Time frame: Baseline, Week 12

Aspartate Aminotransferase (AST)

Serum AST level will be measured to assess hepatocellular integrity.

Time frame: Baseline, Week 12

Fasting Blood Glucose

Fasting blood glucose concentration will be measured to assess glycemic status.

Time frame: 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.

Time frame: Baseline, Week 12

Left Atrial Volume Index (LAVI)

LAVI will be measured to assess changes in left atrial remodeling.

Time frame: Baseline, Week 12

Left Ventricular Mass Index (LVMI)

LVMI will be measured to assess changes in left ventricular hypertrophy.

Time frame: Baseline, Week 12

Pulmonary Artery Systolic Pressure (PASP)

PASP will be measured to assess changes in pulmonary artery pressure.

Time frame: Baseline, Week 12

E/e' Ratio

The E/e' ratio will be measured to assess changes in left ventricular filling pressure.

Time frame: Baseline, Week 12

Total Body Fat Mass

Body fat mass will be measured to assess changes in adiposity.

Time frame: Baseline, Week 12

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts