Evaluation of GeranylGeranylAcetone in Heart Failure With Preserved Ejection Fraction
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Filling pressures
研究概览
简要总结
The goal of this double-blind randomized, placebo-controlled cross-over trial is to evaluate the effectiveness of GerenylGeranylAcetone (GGA) in patients with Heart Failure with a preserved ejection fraction.
The main questions it aims to answer are:
- What is the effect of GGA on diastolic function?
- What is the effect of GGA on endothelial function?
Main study tasks:
- Participants will be treated with either GGA or placebo for 13 weeks. After this they will have a break (wash-out) period for 6 weeks and then cross over to the other study arm.
- Cardiac function will be measured using echocardiogram in all participants
- Renal measurements and endothelial measurements will be performed on the participants.
- Participants will perform a 5 minute walking distance test for functional capacity.
- Participants will fill out questionnaires to score signs & symptoms.
Researchers will compare the patients to themselves to see if the drug improves diastolic- and endothelial function.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age≥ 50 years
- •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 < 9 cm/s) OR E/e' >13 OR TR velocity at rest >2,8m/s.
- •Pulmonary capillary wedge pressure (PCWP) >15 mmHg and/or >25 mmHg during exercise.
排除标准
- •Current acute decompensated heart failure, requiring hospitalization or augmented therapy with intravenous diuretics, vasodilators, and/or inotropic drugs
- •Acute coronary syndrome, transient ischemic attack/cerebrovascular accident, major surgery within the previous 3 months
- •Hemoglobin <9 g/dl at screening
- •LVEF <40% measured at any time point in the history of the patient
- •History of mitral valve repair or replacement
- •Presence of significant valvular disease defined as mitral valve regurgitation defined as grade ≥ 3+ MR; tricuspid valve regurgitation defined as grade ≥ 2+ TR; aortic valve disease defined as ≥ 2+ AR or > moderate AS
- •Acute myocarditis within 3 months prior to randomization
- •Infiltrative cardiomyopathy
- •Genetic cardiomyopathy
- •Severe pulmonary disease requiring home oxygen or chronic oral steroid therapy
- •Precapillary pulmonary hypertension
- •BMI >40 kg/m2
- •Estimated glomerular filtration rate (GFR) <20 ml/min or >90 ml/min
- •History of solid organ transplantation including kidney transplantation
- •Atrial fibrillation or atrial flutter with resting ventricular rate >110 bpm
- •Not able to undergo the complete study protocol
- •Doubt about compliance
- •Pre-menopausal women who are nursing, pregnant, or of child-bearing potential and not practicing an acceptable method of birth control
- •Chronic absorption problems
- •Proven allergy for lactose products or cow-milk.
- •Proven allergy for Iodide-containing contrast, Iohexol or PAH.
- •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
- •Currently enrolled in another investigational device or drug trial
- •Estimated life expectancy <1 year
研究组 & 干预措施
Experimental arm
Patients will receive 13 weeks of experimental treatment, followed by a 7 week wash-out period, continuing with 13 weeks of placebo as per crossover design.
干预措施: Iohexol measurement (Diagnostic Test)
Experimental arm
Patients will receive 13 weeks of experimental treatment, followed by a 7 week wash-out period, continuing with 13 weeks of placebo as per crossover design.
干预措施: Geranylgeranylacetone (GGA) (Drug)
Experimental arm
Patients will receive 13 weeks of experimental treatment, followed by a 7 week wash-out period, continuing with 13 weeks of placebo as per crossover design.
干预措施: Echocardiography (Diagnostic Test)
Experimental arm
Patients will receive 13 weeks of experimental treatment, followed by a 7 week wash-out period, continuing with 13 weeks of placebo as per crossover design.
干预措施: 6-minute walking distance test (Diagnostic Test)
Experimental arm
Patients will receive 13 weeks of experimental treatment, followed by a 7 week wash-out period, continuing with 13 weeks of placebo as per crossover design.
干预措施: EndoPAT (Diagnostic Test)
Experimental arm
Patients will receive 13 weeks of experimental treatment, followed by a 7 week wash-out period, continuing with 13 weeks of placebo as per crossover design.
干预措施: Para-amino Hippuric Acid test (Diagnostic Test)
Experimental arm
Patients will receive 13 weeks of experimental treatment, followed by a 7 week wash-out period, continuing with 13 weeks of placebo as per crossover design.
干预措施: Electrocardiogram (Diagnostic Test)
Placebo arm
Patients will receive 13 weeks of placebo treatment, followed by a 7 week wash-out period, continuing with 13 weeks of experimental treatment as per crossover design.
干预措施: Iohexol measurement (Diagnostic Test)
Placebo arm
Patients will receive 13 weeks of placebo treatment, followed by a 7 week wash-out period, continuing with 13 weeks of experimental treatment as per crossover design.
干预措施: Geranylgeranylacetone (GGA) (Drug)
Placebo arm
Patients will receive 13 weeks of placebo treatment, followed by a 7 week wash-out period, continuing with 13 weeks of experimental treatment as per crossover design.
干预措施: Echocardiography (Diagnostic Test)
Placebo arm
Patients will receive 13 weeks of placebo treatment, followed by a 7 week wash-out period, continuing with 13 weeks of experimental treatment as per crossover design.
干预措施: 6-minute walking distance test (Diagnostic Test)
Placebo arm
Patients will receive 13 weeks of placebo treatment, followed by a 7 week wash-out period, continuing with 13 weeks of experimental treatment as per crossover design.
干预措施: EndoPAT (Diagnostic Test)
Placebo arm
Patients will receive 13 weeks of placebo treatment, followed by a 7 week wash-out period, continuing with 13 weeks of experimental treatment as per crossover design.
干预措施: Para-amino Hippuric Acid test (Diagnostic Test)
Placebo arm
Patients will receive 13 weeks of placebo treatment, followed by a 7 week wash-out period, continuing with 13 weeks of experimental treatment as per crossover design.
干预措施: Electrocardiogram (Diagnostic Test)
结局指标
主要结局
Filling pressures
时间窗: after 13 weeks of treatment
Changes in echocardiography determined filling pressures (E/e')?
Endothelial function
时间窗: after 13 weeks of treatment
Changes in EndoPAT®-derived reactive hyperemia index (RHI)
次要结局
- Left atrial global strain(After 13 weeks of treatment)
- Pulmonary Artery Pressure(After 13 weeks of treatment)
- Nitrate (microvascular marker)(After 13 weeks of treatment)
- Left Ventricular global longitudinal strain(Ater 13 weeks of treatment)
- Measured Glomerular Filtration Rate (mGFR)(After 13 weeks of treatment)
- Patient reported symptoms(After 13 weeks of treatment)
- Urine Albumine Creatinin Ratio(After 13 weeks of treatment)
- Left atrial volumes(After 13 weeks of treatment)
- Left atrial emptying fractions(After 13 weeks of treatment.)
- CRP (inflammatory biomarker)(After 13 weeks of treatment)
- H2S (microvascular marker)(After 13 weeks of treatment)
- Right Ventricular systolic function(After 13 weeks of treatment)
- Left Ventricular Myocardial relaxation(Ater 13 weeks of treatment)
- Left Ventricular distensibility(After 13 weeks of treatment)
- Quality of life assessment(After 13 weeks of treatment.)
- Functional capacity(After 13 weeks of treatment.)
- Nitrosated hemoglobin (microvascular marker)(After 13 weeks of treatment)
- Endothelin-1 (microvascular marker)(After 13 weeks of treatment)
- Neutrophil gelatinase associated lipocalin (NGAL)(After 13 weeks of treatment)
- Effective Renal Plasma Flow (ERPF)(After 13 weeks of treatment)
- Renal vascular resistance (RVR)(After 13 weeks of treatment)
- Kidney Injury marker 1 (KIM-1)(After 13 weeks of treatment)
研究者
M. Louis Handoko
MD, PhD, Principal investigator
VU University of Amsterdam