NCT05138575招募中2 期
SGLT2i and KNO3 in HFpEF - The SAK HFpEF Trial
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 53
- 试验地点
- 1
- 主要终点
- Submaximal Exercise Endurance
研究概览
简要总结
This study will test whether pharmacologic agents that may improve mitochondrial function and energy fuel metabolism [Empagliflozin (Empa)], with and without additional supplements that increase perfusion and fatty acid oxidation [Potassium Nitrate (KNO3)], improve submaximal exercise endurance and skeletal muscle oxidative phosphorylation capacity (SkM OxPhos) in participants with Heart Failure with Preserved Ejection Fraction (HFpEF).
详细描述
This study will test whether Empagliflozin (Empa), with and without Potassium Nitrate (KNO3), improves submaximal exercise endurance, skeletal muscle oxidative phosphorylation capacity (SkM OxPhos), intramuscular perfusion, and changes in the skeletal muscle metabolome, proteome, and respiration in participants with Heart Failure with Preserved Ejection Fraction (HFpEF).
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)
盲法说明
All personnel will be masked except for the IDS pharmacist dispensing the drugs.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1. NYHA Class II-III symptoms
- •Left ventricular ejection fraction >= 50%
- •Stable medical condition for at least 2 weeks, as per investigator judgment
- •Prior or current evidence for elevated filling pressures, as evidenced by at least one of the following:
- •a. Mitral early (E)/septal tissue annular (e') velocity ratio > 8, in the context of a septal e' velocity <=7 cm/s or a lateral e' <= 10 cm/s, in addition to one of the following: i. Large left atrium (LA volume index > 34 mL/m2) ii. Chronic loop diuretic use for control of symptoms iii. Elevated natriuretic peptides within the past year (e.g., NTproBNP > 125 pg/mL in sinus rhythm or > 375 pg/mL if in atrial fibrillation) b. Mitral E/e' ratio > 14 at rest or during exercise c. Elevated invasively-determined filling pressures previously (resting left ventricular end-diastolic pressure >= 16 mm Hg or pulmonary capillary wedge pressure >= 15 mmHg; or PCWP/LVEDP >= 25 mmHg with exercise) d. Prior episode of acute heart failure requiring IV diuretics
排除标准
- •Age <18 years old
- •Pregnancy: Women of childbearing potential will undergo a urine pregnancy test during the screening visit.
- •Treatment with organic nitrates or phosphodiesterase inhibitors that cannot be interrupted
- •Uncontrolled atrial fibrillation, as defined by a resting atrial fibrillation heart rate > 100 beats per minute at the time of the baseline assessment
- •Hemoglobin < 10 g/dL
- •Subject inability/unwillingness to exercise
- •Moderate or greater left sided valvular disease (mitral regurgitation, aortic stenosis, aortic regurgitation), mild or greater mitral stenosis, severe right-sided valvular disease
- •Known hypertrophic, infiltrative, or inflammatory cardiomyopathy
- •Clinically significant pericardial disease, as per investigator judgment
- •Current angina due to clinically significant epicardial coronary disease, as per investigator judgment
- •Acute coronary syndrome or coronary intervention within the past 2 months
- •Primary pulmonary artery hypertension (WHO Group 1 Pulmonary Arterial Hypertension)
- •Clinically significant lung disease as defined by: Chronic Obstructive Pulmonary Disease Stage III or greater GOLD criteria (FEV1<50%), treatment with oral steroids within the past 6 months for an exacerbation of obstructive lung disease, current use of supplemental oxygen aside from nocturnal oxygen for the treatment of obstructive sleep apnea.
- •- Desaturation to <90% on the baseline maximal effort cardiopulmonary exercise test will also be grounds for exclusion
- •Clinically-significant ischemia, as per investigator's judgement, on stress testing without either (1) subsequent revascularization, (2) an angiogram demonstrating the absence of clinically significant epicardial coronary artery disease, as per investigator judgment; (3) a follow-up 'negative' stress test, particularly when using a more specific technique (i.e., a negative perfusion imaging test following a 'positive' ECG stress test)
- •- Exercise-induced regional wall motion abnormalities on the echocardiographic assessment during the baseline maximal effort cardiopulmonary exercise test will also be exclusionary
- •Left ventricular ejection fraction < 45% on a prior echocardiogram or cardiac MRI, unless the reduced LVEF occurred within the context of an uncontrolled supraventricular arrhythmia, with return of a normal ejection fraction following treatment of the arrhythmia
- •Significant liver disease impacting synthetic function or volume control (ALT/AST > 3x ULN, Albumin < 3.0 g/dL)
- •eGFR < 30 mL/min/1.73m
- •Methemoglobin > 5%
- •Serum potassium > 5.0 mEq/L on baseline testing
- •Type I Diabetes
- •History of ketoacidosis
- •Current use of, or prior intolerance to, an SGLT2i
- •Ongoing maintenance of a 'Ketogenic Diet' (low carbohydrate, high fat)
- •Allergy to beets
- •Severe right ventricular dysfunction
- •Baseline resting seated systolic blood pressure > 180 mmHg or < 100 mmHg
- •Persistently low or high seated blood pressure or orthostatic blood pressure response to the transition from supine to standing (>20 mmHg reduction in systolic blood pressure 2-3 minutes after standing, or a fall in SBP to < 90 mmHg) at the baseline visit
- •Active participation in another study that utilizes an investigational agent (observational studies/registries allowed)
- •Any condition that, in the opinion of the investigator, may interfere with the completion/performance of the study. This may include comorbid or psychiatric conditions that may impede successful completion of the protocol, or logistical concerns (e.g., inability to travel to the exercise unit).
研究组 & 干预措施
Potassium Chloride (KCl) + Placebo for Empa
Placebo Comparator
Potassium Chloride (6 mmol three times daily) + Placebo for Empagliflozin
Placebo arm will be 6 weeks in duration followed by a 2 week washout period.
干预措施: Potassium Chloride + Placebo for Empagliflozin (Drug)
Empagliflozin + Potassium Chloride (KCl)
Active Comparator
Empagliflozin (10 mg daily) + Potassium Chloride (6 mmol three times daily)
Active arm will be 6 weeks in duration followed by a 2 week washout period.
干预措施: Empagliflozin + Potassium Chloride (Drug)
Empagliflozin + Potassium Nitrate (KNO3)
Active Comparator
Empagliflozin (10 mg daily) + Potassium Nitrate (6 mmol three times daily)
Active arm will be 6 weeks in duration followed by a 2 week washout period.
干预措施: Empagliflozin + Potassium Nitrate (Drug)
结局指标
主要结局
Submaximal Exercise Endurance
时间窗: Week 6
Time to exhaustion while exercising at 75% peak workload
次要结局
- Intramuscular Perfusion(Week 6)
- Vasodilatory Reserve(Week 6)
- VO2 Kinetics(Week 6)
- Ambulatory Physical Activity(Week 6)
- Muscle Tissue Respirometry(Week 6)
- VO2 Efficiency(Week 6)
- Venous Substrate Concentration(Week 6)
- Respiratory Exchange Ratio(Week 6)
- Arteriovenous O2 content difference(Week 6)
- KCCQ Overall Summary Score(Week 6)
- Muscle Proteome(Week 6)
- Muscle Metabolome(Week 6)
- Skeletal Muscle Oxidative Capacity(Week 6)
- Peak VO2 during Submaximal Exercise(Week 6)
- VO2 Kinetics(Week 6)
- VO2 Efficiency(Week 6)
- Vasodilatory Reserve(Week 6)
- Venous Substrate Concentration(Week 6)
- Respiratory Exchange Ratio(Week 6)
- KCCQ Overall Summary Score(Week 6)
- Ambulatory Physical Activity(Week 6)
- Muscle Tissue Respirometry(Week 6)
- Muscle Proteome(Week 6)
- Muscle Metabolome(Week 6)
- Skeletal Muscle Oxidative Capacity(Week 6)
- Arteriovenous O2 content difference(Week 6)
- Intramuscular Perfusion(Week 6)
研究者
Payman Zamani, MD
Principle Investigator
University of Pennsylvania
研究点 (1)
Loading locations...
相似试验
招募中
2 期
Matching Perfusion and Metabolic Activity in HFpEFHeart Failure With Preserved Ejection FractionNCT04913805University of Pennsylvania53
终止
不适用
Tecfidera and MRI for Brain Energy in MSMultiple SclerosisNCT02644083Oregon Health and Science University4
已完成
1 期
EPI-743 for Metabolism or Mitochondrial DisordersMitochondrial DiseaseNeurologyMyopathyNCT01642056National Human Genome Research Institute (NHGRI)20
招募中
早期 1 期
Ketones, SGLT2, HFrEFType2diabetesHeart Failure With Reduced Ejection FractionNCT06229678The University of Texas Health Science Center at San Antonio71
招募中
早期 1 期
SGLT2 Inhibitors, Ketones, and Cardiovascular Benefit Research PlanType2 DiabetesHeart Failure With Preserved Ejection FractionNCT05057806The University of Texas Health Science Center at San Antonio30