Comparing ketogenic and low-fat diets for heart failure patients

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

This study is testing whether a low carbohydrate ketogenic diet or a low-fat diet can help people with heart failure feel better and exercise more effectively over six months.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Ohio State University (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Columbus, Ohio)
• Trial ID: NCT06081543 on ClinicalTrials.gov

What this trial studies

This study evaluates the effects of a low carbohydrate ketogenic diet versus a low-fat mixed diet on exercise tolerance in patients with heart failure with preserved ejection fraction, diabetes, pre-diabetes, metabolic syndrome, or obesity. Participants will be randomized to one of the two diets for a total of six months, with the first six weeks involving provided groceries and dietary coaching. After this initial period, participants will transition to a free-living diet while receiving educational materials and ongoing support from a dietitian. Key health metrics, including ketone and glucose levels, weight, and blood pressure, will be monitored throughout the study.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 to 80 with heart failure, a BMI of 25 or higher, and stable medical therapy.

Not a fit: Patients with severe heart failure symptoms or those not willing to adhere to dietary changes may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a dietary intervention that improves exercise tolerance and overall health in heart failure patients.

How similar studies have performed: Other studies have shown promising results with dietary interventions in heart failure, suggesting potential for success in this approach.

Eligibility criteria

Inclusions:

1. Age ≥ 18 years old and ≤ 80 years old \& willingness to be randomized to either diet.
2. NYHA class I - III for at least 3 months.
3. Ejection fraction ≥40% by biplane 2D, or 3D echo, or CMR
4. 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.
5. 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).
6. Dose of oral diuretics changes allowed but must be stable for 1 week prior to randomization.
7. 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.
8. Ability to participate in exercise treadmill testing.
9. Ability to sign written consent.

Exclusions:

1. Women who are pregnant, current breast-feeding, or have intention to become pregnant while in the study.
2. Known allergy or sensitivity to gadolinium-based contrast agents.
3. Implanted pacemaker, cardioverter defibrillator, Cardiac resynchronization therapy, left ventricular assist device.
4. Other metallic implants/aneurysm clips that are contraindicated in MRI.
5. Claustrophobia
6. History of severe kidney disease of estimated glomerular filtration rate (eGFR) \<30 ml/kg/1.73m2.
7. Type I diabetes.
8. History of diabetic ketoacidosis.
9. Prior diagnosis of oxygen dependent pulmonary disease.
10. Body Mass Index (BMI) \< 25.
11. Recent acute myocardial infarction or acute coronary syndrome (30 days).
12. 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.
13. Left ventricular ejection fraction \< 50%.
14. Uncontrolled systemic systolic blood pressure (SBP)/diastolic blood pressure (DBP) hypertension (SBP \>180 or DBP \>110 mmHg).
15. Severe stenotic or regurgitant valvular heart disease, expected to lead to surgery during the study period.
16. Persistent atrial fibrillation.
17. History of uncontrolled or untreated ventricular arrhythmias.
18. Cardiovascular diseases or treatments that increase the unpredictability of or change the subject's clinical course, independent of heart failure.
19. Heart transplant or listing for heart transplant.
20. 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.
21. 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.
22. Hemoglobin of \<9 g/dL at screening.
23. 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.
24. 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.
25. Gastrointestinal surgery or gastrointestinal disorder that might interfere with diet. Prior bariatric surgery allowed if weight-stable for past 3 months.
26. 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).
27. Presence of any disease other than heart failure that results in a life expectancy of \<1 year (in the opinion of the investigator).
28. History or recurrent severe hypokalemia, potassium \< 3.0 mg/dL.
29. Current enrollment or completion within 30 days of an investigational device or drug study.
30. 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.
31. Any other clinical condition that might jeopardize subject safety during participation in this study or prevent the subject from adhering to the study protocol.
32. Unable or unwilling to follow guidelines of assigned diet group, including inability to purchase food.
33. Unable to participate in the comprehensive diet program, including biometric data acquisition and data entry.
34. The subject cannot currently be on a low-carb diet plan. 30-day washout would be required.
35. 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.
36. Refusal to consent.

Where this trial is running

Columbus, Ohio

• The Ross Heart Hospital — Columbus, Ohio, United States (Recruiting)

Study contacts

• Principal investigator: Yuchi Han, MD, MMSc — Ohio State University
• Study coordinator: Debbie Scandling, BS

Conditions Heart Failure With Preserved Ejection Fraction; Ketogenic Diet; Heart Failure