A Prospective Randomized Unblinded Study of Ketogenetic Versus Mixed Diet on Exercise Tolerance in Subjects With the Metabolic Phenotype of Heart Failure With Preserved Ejection Fraction
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 90
- 试验地点
- 2
- 主要终点
- Changes in maximal exercise performance
研究概览
简要总结
This study is being done to evaluate the effects of a low carbohydrate ketogenic diet (KD) versus a low-fat diet (MD) on exercise tolerance in participants with heart failure with normal pumping function and diabetes or pre-diabetes, or metabolic syndrome, or obesity.
详细描述
Participants will be randomized to either a ketogenic diet (KD), or a low-fat diet (MD).
Participants will eat the specified diet for a period of 6-months and be supported by dietary coaching. All foods and/or groceries will be provided at no cost for the first six weeks of the study.
After the initial 6 weeks, and for the next 20-22 weeks, participants will change into a free-living diet period where food will not be supplied but they will receive educational materials and frequent coaching from a dietitian to help maintain the specified diet. Both diets are based on a slight reduction in dietary caloric requirements, so some weight loss should occur over the 6-month intervention.
Ketone and glucose values will be monitored over a 2-week period at baseline, during the conclusion of the first 6 weeks, as well as the final 2-week period at the end of the 6-month study. Participants will apply a sensor one week prior to starting the study to capture one week of baseline metabolic status and the first week of the diet. Another sensor will be applied for week 5 to week 7, and a third sensor for weeks 25 to 26 at the end of the diet. Weight, blood pressure, oxygen saturation, resting heart rate, and activity level will also be monitored.
Throughout the duration of the study, participants will be monitored closely, and diabetes and diuretics medications adjusted by physicians involved in this study. Other medications will be continued and guided by your regular physicians. Both groups will be supported from the research physicians on a weekly basis (including medication changes). The duration of the study is expected to last for approximately 6-month.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusions:
- •Age ≥ 18 years old and ≤ 80 years old & willingness to be randomized to either diet.
- •NYHA class I - III for at least 3 months.
- •Ejection fraction ≥40% by biplane 2D, or 3D echo, or CMR
- •Echo findings of abnormal or indeterminant diastolic function or right heart catheterization (RHC) data: At rest: mean pulmonary capillary wedge pressure (PCWP) > 15 mmHg. pulmonary vascular resistance (PVR) < 3 Wood Units.
- •Stable medical therapy for at least 3 months as determined by the treating physician (no new cardiac or diabetic medications within 3 months of enrollment or during enrollment and dosage should be stable for 1 month prior to enrollment).
- •Dose of oral diuretics changes allowed but must be stable for 1 week prior to randomization.
- •Body Mass Index (BMI) ≥ 25 or Type 2 Diabetes Mellitus or prediabetes (fasting glucose of 100 - 125 mg/dL or glycated hemoglobin (A1C) 5.7-6.4% or metabolic syndrome.
- •Ability to participate in exercise treadmill testing.
- •Ability to sign written consent.
- •Exclusions:
- •Women who are pregnant, current breast-feeding, or have intention to become pregnant while in the study.
- •Known allergy or sensitivity to gadolinium-based contrast agents.
- •Implanted pacemaker, cardioverter defibrillator, Cardiac resynchronization therapy, left ventricular assist device.
- •Other metallic implants/aneurysm clips that are contraindicated in MRI.
- •Claustrophobia
- •History of severe kidney disease of estimated glomerular filtration rate (eGFR) <30 ml/kg/1.73m
- •Type I diabetes.
- •History of diabetic ketoacidosis.
- •Prior diagnosis of oxygen dependent pulmonary disease.
- •Body Mass Index (BMI) <
- •Recent acute myocardial infarction or acute coronary syndrome (30 days).
- •Or recent (within 30 days) or planned (within 30 days) cardiac revascularization History of left main disease, severe triple vessel disease, coronary artery bypass graft surgery.
- •Left ventricular ejection fraction < 50%.
- •Uncontrolled systemic systolic blood pressure (SBP)/diastolic blood pressure (DBP) hypertension (SBP >180 or DBP >110 mmHg).
- •Severe stenotic or regurgitant valvular heart disease, expected to lead to surgery during the study period.
- •Persistent atrial fibrillation.
- •History of uncontrolled or untreated ventricular arrhythmias.
- •Cardiovascular diseases or treatments that increase the unpredictability of or change the subject's clinical course, independent of heart failure.
- •Heart transplant or listing for heart transplant.
- •Cardiomyopathy based on infiltrative diseases (e.g. amyloidosis), accumulation diseases (e.g. haemochromatosis, Fabry disease), muscular dystrophies, cardiomyopathy with reversible causes (e.g. stress cardiomyopathy), hypertrophic obstructive cardiomyopathy or known pericardial constriction.
- •Acute decompensated heart failure requiring intravenous diuretics, vasodilators, inotropic agents or mechanical support within 1 week of screening and during the screening period prior to randomization.
- •Hemoglobin of <9 g/dL at screening.
- •Major surgery (major according to the investigator's assessment) performed within 90 days prior to screening, or major scheduled elective surgery (e.g. hip replacement) within 90 days after screening.
- •Acute or chronic liver disease, defined by serum levels of transaminases or alkaline phosphatase more than three times the upper limit of normal at screening.
- •Gastrointestinal surgery or gastrointestinal disorder that might interfere with diet. Prior bariatric surgery allowed if weight-stable for past 3 months.
- •Any documented active or suspected malignancy or history of malignancy within 2 years prior to screening, except appropriately treated basal cell carcinoma of the skin, in situ carcinoma of the uterine cervix, or low-risk prostate cancer (subjects with pre-treatment prostate-specific antigen levels of <10 ng/mL, and biopsy Gleason scores of ≤6 and clinical stage T1c or T2a).
- •Presence of any disease other than heart failure that results in a life expectancy of <1 year (in the opinion of the investigator).
- •History or recurrent severe hypokalemia, potassium < 3.0 mg/dL.
- •Current enrollment or completion within 30 days of an investigational device or drug study.
- •Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, will make the subject unlikely to fulfill the study requirements or complete the trial.
- •Any other clinical condition that might jeopardize subject safety during participation in this study or prevent the subject from adhering to the study protocol.
- •Unable or unwilling to follow guidelines of assigned diet group, including inability to purchase food.
- •Unable to participate in the comprehensive diet program, including biometric data acquisition and data entry.
- •The subject cannot currently be on a low-carb diet plan. 30-day washout would be required.
- •Patient has to have stable weight over the past 3 months (± 5% total body weight). If no weight was recorded in the past 3 months, will have 1 month lead in time for wash out.
- •Refusal to consent.
排除标准
- 未提供
研究组 & 干预措施
Ketogenic Diet
This arm will be provided food to induce a state of nutritional ketosis in each person as defined as blood Beta-hydroxybutyrate (3-OHB) ≥0.5 millimoles (mM), which will require most participants to consume <50 g/day carbohydrate and 1.5g/kg reference weight protein. Fat will comprise the remaining calories with an emphasis on monounsaturated and saturated sources from whole foods.
干预措施: Ketogenic diet (Dietary Supplement)
Low-fat mixed Diet
This arm will be provided food consisting of ~25% fat, and the remaining calories from carbohydrate (~55% after accounting for protein at ~20%).
干预措施: Low-fat Mixed diet (Dietary Supplement)
结局指标
主要结局
Changes in maximal exercise performance
时间窗: baseline, 6 weeks, and end of the study (26 weeks)
Participants will undergo VO2 max testing, conducted by trained professionals. VO2 max testing analyses will determine changes in maximal exercise performance
次要结局
- Change in New York Heart Association (NYHA) class(baseline, 6 weeks, and end of the study (26 weeks))
- Change in Quality of Life Questionnaire(baseline, 6 weeks, and end of the study (26 weeks))
- Change in Cardiac Output (L/min) via cardiovascular magnetic resonance imaging (CMR) .(baseline, 6 weeks, and end of the study (26 weeks))
- Change Stroke Volume(mL) via cardiovascular magnetic resonance imaging (CMR)(baseline, 6 weeks, and end of the study (26 weeks))
- Percent change in ejection fraction via cardiovascular magnetic resonance imaging (CMR)(baseline, 6 weeks, and end of the study (26 weeks))
- Metabolic Panel(baseline, 6 weeks, and end of the study (26 weeks))
- Lipid Panel(baseline, 6 weeks, and end of the study (26 weeks))
- B-natriuretic peptide (BNP)(baseline, 6 weeks, and end of the study (26 weeks))
- Continuous glucose/ketone monitor (CGM/CKM)(Up to ~ 26 weeks)
研究者
Yuchi Han
Professor-Clinical, Cardiovascular Medicine
Ohio State University