Acute Effects of Exogenous Ketone Ester Administration in Heart Failure
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Maximal Exercise Capacity (Peak VO2) Assessed by Cardiopulmonary Exercise Testing
研究概览
简要总结
The purpose of this study is to test whether a ketone ester drink will improve exercise in people with heart failure (HF) compared to a placebo. In HF, patients are limited in their ability to do all the things they want to do, and exercise as much as they would like, due to becoming tired and short of breath early. There may be several reasons why these symptoms occur.
There is some evidence that in addition to problems with the heart, patients with HF also have problems with their arteries and muscles that affect their ability to exercise. Ketones have been shown to improve exercise capacity in healthy volunteers, which may be related to effects on the heart function or on muscles. An infusion of ketones through an intravenous (IV) line has also been shown to significantly improve heart function, but whether a drink can produce similar improvements in HF patients is not known. This drink has been given status by Food and Drug Administration as "generally regarded as safe".
The use of DeltaG in this study is experimental. DeltaG has not been approved by the Food and Drug Administration (FDA) for the use being evaluated in this study.
详细描述
This is a randomized, crossover trial of ketone ester versus placebo in 20 patients with heart failure with preserved ejection fraction. Participants come for a baseline assessment. If they meet eligibility criteria, they are randomized to receive ketone ester first or placebo first. After approximately a week washout period, participants return for the last visit to receive the product they did not receive at the previous visit.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Left ventricular ejection fraction ≥ 50%
- •Evidence for elevated filling pressures as follows (at least one of the following between a-d):
- •a. Mitral early (E)/mitral septal tissue annular (e') velocity ratio > 8 in addition to one of the following: i. Large left atrium (LA>4.0 cm width or LA volume index >34 mL/m2) ii. Chronic loop diuretic use for control of symptoms iii. Elevated natriuretic peptides within the past year (NT-proBNP>125 pg/ml or BNP>35 pg/ml) b. Mitral E/e' ratio > 14 at rest or with 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 with evidence of volume overload on exam/radiology or elevated natriuretic peptides.
排除标准
- •Intentional ketogenic (high fat, low carbohydrate) diet in the last week or use of ketogenic medications (SGLT2 inhibitors)
- •Significant liver disease (liver function tests > 3x upper limit of normal, cirrhosis) or alcohol abuse disorder (>14 drinks/week).
- •Contraindications to stress testing, conditions that limit exercise, and other clinically-significant causes of exertional limitation (claudication with peripheral artery disease, atrial fibrillation and heart rate >110 at rest, systolic blood pressure>180 mmHg or diastolic blood pressure>110 mmHg, infiltrative/hypertrophic/inflammatory cardiomyopathy, clinically significant pericardial disease, joint or neuromuscular disease that precludes exercise, acute coronary syndrome within the last 2 months, estimated glomerular filtration rate<30 mL/min/1.73 m2, and hemoglobin < 9 mg/dL).
- •Clinically significant lung disease. This would be defined by severe obstructive lung disease (Gold stage 3), a requirement for supplemental oxygen, or chronic obstructive pulmonary disease with an exacerbation requiring steroids or antibiotics within the last 2 months.
- •>= Moderate aortic stenosis, >mild mitral stenosis, >= moderate aortic or mitral regurgitation on screening echocardiogram
- •Type 1 diabetes mellitus
- •Pregnant women. Due to unknown affects of nutritional ketosis in pregnant women, pregnancy will be an exclusion. Accordingly, women of childbearing age with a menstrual cycle within the past year will be asked to submit a urine specimen for pregnancy testing.
- •Angina due to epicardial coronary disease or known presence of clinically-significant, unrevascularized epicardial coronary disease, in the investigator's opinion.
- •Prior reduced LVEF to < 45%
研究组 & 干预措施
Ketone ester
(R)-3-hydroxybutyl (R)-3-hydroxybutyrate, a ketone ester
干预措施: Ketone ester (Dietary Supplement)
Placebo
KE-free solution
干预措施: placebo drink (Dietary Supplement)
结局指标
主要结局
Maximal Exercise Capacity (Peak VO2) Assessed by Cardiopulmonary Exercise Testing
时间窗: Assessed 60 minutes after the intervention.
Peak VO2
Submaximal Exercise Capacity (Exercise Time at 75% of Peak Workload) Assessed by Cardiopulmonary Exercise Testing.
时间窗: Assessed 30 minutes after the intervention.
Exercise time at 75% of peak workload
次要结局
- Percent Change in Systemic Vascular Resistance With Exercise(Assessed 60 minutes after the intervention.)
- Substrate Utilization (Reflected by the Respiratory Exchange Ratio) Assessed by Cardiopulmonary Exercise Testing.(Assessed 60 minutes after the intervention.)
- VO2 Efficiency (Total Work Performed Over Oxygen Consumed) During Submaximal Cardiopulmonary Exercise Testing.(Assessed 60 minutes after the intervention.)
- Presence of Exercise-induced Arrhythmias (Significant Atrial or Ventricular Arrhythmias)(Assessed throughout the study visit date after the intervention is given (until leaving the research study center that day).)
研究者
Kenneth B Margulies
Professor of Medicine
University of Pennsylvania