Heart Failure with preserved ejection fraction.
Conditions
Interventions
Trade Name: Teprenone
Product Name: GeranylGeranylAcetone
Pharmaceutical Form: Oral drops, liquid
Pharmaceutical form of the placebo: Oral liquid
Route of administration of the placebo: Oral use
Sponsors
Amsterdam UMC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be eligible to participate in this study, a subject must meet all of the following criteria: 1. Age= 50 years 2. Patients with a diagnosis of symptomatic chronic heart failure (New York Heart Association class II or III) AND preserved systolic LV function (LV ejection fraction or LVEF = 50%) documented within the last 6 months AND evidence of diastolic LV dysfunction with at least 1 out of the following 4 criteria: - HFA-PEFF score =5 - H2FPEF score =6 - HFpEF according to the 2021 ESC HF Guidelines (NT-proBNP>125 pg/ml AND either LV mass indexed or LVMI >95 g/m2 for women and >115 g/m2 for men OR left atrial volume indexed or LAVI >34 ml/m2 OR mean e; septal/lateral 13) OR TR velocity at rest > 2.8 m/s. - Pulmonary capillary wedge pressure (PCWP) >15 mmHg and/or >25 mmHg during exercise Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1. Current acute decompensated heart failure, requiring hospitalization or augmented therapy with intravenous diuretics, vasodilators, and/or inotropic drugs 2. Acute coronary syndrome, transient ischemic attack/cerebrovascular accident, major surgery within the previous 3 months 3. Hemoglobin moderate AS 7. Acute myocarditis within 3 months prior to randomization 8. Infiltrative cardiomyopathy 9. Genetic cardiomyopathy 10. Severe pulmonary disease requiring home oxygen or chronic oral steroid therapy 11. Precapillary pulmonary hypertension 12. BMI >40 kg/m2 13. Estimated glomerular filtration rate (GFR) 90 ml/min 14. History of solid organ transplantation including kidney transplantation 15. Atrial fibrillation or atrial flutter with resting ventricular rate >110 bpm 16. Not able to undergo the complete study protocol 17. Doubt about compliance 18. Pre-menopausal women who are nursing, pregnant, or of child-bearing potential and not practicing an acceptable method of birth control 19. Chronic absorption problems 20. Proven allergy for lactose products or cow-milk. 21. Proven allergy for Iodide-containing contrast, Iohexol or PAH. 22. Any documented or suspected malignancy or history of malignancy within 1 year prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of the cervix 23. Currently enrolled in another investigational device or drug trial 24. Estimated life expectancy <1 year
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objectives To study whether Geranyl-Geranyl Acetone (GGA) reduces left ventricular (LV) diastolic dysfunction in patients with HFpEF compared to placebo (and to assess/confirm its effectiveness and safety in patients with HFpEF) ;Secondary Objective: Secondary objectives •To assess whether GGA improves endothelial function in patients with HFpEF compared to placebo. •To assess whether GGA improves renal (hemodynamic) function in patients with HFpEF compared to placebo •To assess whether GGA improves self-reported quality of life and exercise tolerance in patients with HFpEF compared to placebo ;Primary end point(s): 1.Does GGA-treatment improve LV diastolic function in HFpEF, measured by echocardiography derived filling pressures (E/e’)? 2.Does GGA-treatment improve endothelial function, measured by EndoPAT®-derived reactive hyperemia index (RHI)? ;Timepoint(s) of evaluation of this end point: After 13 weeks of treatment with GGA/placebo. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Additional echocardiographic measures: • Change in echocardiographically determined left atrial (LA) indexed volumes: (LAVImax, LAVImin, LAVIpre-A) and function (LA global strain and LA emptying fractions (reservoir, conduit and booster pump). • Change in echocardiographically determined LV global longitudinal strain. • Change in echocardiographically determined LV myocardial relaxation (e’). • Change in echocardiographically determined LV distensibility, measured by E/e’ and LV end-diastolic volume. • Change in echocardiographically determined right ventricular systolic function (TAPSE, RV S’).Change in echocardiographically determined pulmonary artery pressure. Patient reported outcomes and exercise capacity: • Change in NYHA class between baseline and 13 weeks. • Change in the total symptom score of the KCCQ quality of life assessment between baseline and 13 weeks. • Change in 6-minute walking distance between baseline and 13 weeks. Endothelial function assessment • Change in flow-mediated vasodilatation in the finger, determined by applanation tonometry (EndoPAT®) • Change in endothelium-dependent and -independent vasodilation in skin, determined by iontophoresis of acetylcholine (miochol) and sodium nitroprusside and measured using laser-Doppler (20) • Microvascular and inflammatory biomarkers: Nitrosated hemoglobin (Hb(NO)4), nitrate/nitrite, H2S, CRP, endothelin-1 Kidney endpoints: • Change in iohexol-measured GFR at baseline and 13 weeks of treatment • Change in para-aminohippuric acid-measured effective renal plasma flow (ERPF) • Change in intrakidney hemodynamic function including renal vascular resistance (RVR), glomerular pressure (Pglo), afferent vascular resistance (Ra) and efferent vascular resistance (Re). • Changes in urinary albumin-creatinine ratio (UACR) • Change in serum and urinary neutrophil gelatinase associated lipocalin (NGAL) • Change in serum and urinary kidney injury molecule (KIM)-1 ;Timepo | — |
Countries
Netherlands
Contacts
Public ContactClinical trial information
UMCG
Outcome results
None listed