Ketogenic Diet vs Mixed Diet in Patients With Heart Failure

NCT06081543 | Recruiting DMC

• 2 other identifiers: 2022H0366CDMRP-PR212399-E
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Heart Failure With Preserved Ejection Fraction

Keywords

Ketogenic Diet; Heart Failure

Outcome Measures

Primary Outcomes (1)

• Changes in maximal exercise performance

  Participants will undergo VO2 max testing, conducted by trained professionals. VO2 max testing analyses will determine changes in maximal exercise performance

  baseline, 6 weeks, and end of the study (26 weeks)

Secondary Outcomes (9)

• 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)

• 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)

Study Arms (2)

Ketogenic Diet

EXPERIMENTAL

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.

Dietary Supplement: Ketogenic diet

Low-fat mixed Diet

EXPERIMENTAL

This arm will be provided food consisting of \~25% fat, and the remaining calories from carbohydrate (\~55% after accounting for protein at \~20%).

Dietary Supplement: Low-fat Mixed diet

Interventions

Ketogenic diet DIETARY_SUPPLEMENT

Participants will undertake a controlled feeding intervention. All food will be prepared and delivered to participants by research staff for the first 6 weeks. After that will be a free-living diet period where food will not be supplied but participants will receive educational materials and frequent coaching from a dietitian to help maintain the specified diet. Participants will be asked to exclusively follow the diet in efforts to control any dietary effects.

Ketogenic Diet

Low-fat Mixed diet DIETARY_SUPPLEMENT

Participants will undertake a controlled feeding intervention. All food will be prepared and delivered to participants by research staff for the first 6 weeks. After that will be a free-living diet period where food will not be supplied but participants will receive educational materials and frequent coaching from a dietitian to help maintain the specified diet. Participants will be asked to exclusively follow the diet in efforts to control any dietary effects.

Low-fat mixed Diet

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Ohio State University: lead
• United States Department of Defense: collaborator

Study Sites (1)

The Ross Heart Hospital

Columbus, Ohio, 43210, United States

RECRUITING

MeSH Terms

Conditions

Heart Failure

Interventions

Diet, Ketogenic

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Yuchi Han, MD, MMSc

  Ohio State University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Debbie Scandling, BS

CONTACT

614-688-5623; debbie.scandling@osumc.edu

Alyssa Marie Castillo, MS

CONTACT

614-688-1213; alyssamarie.castillo@osumc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor-Clinical, Cardiovascular Medicine

Study Record Dates

• First Submitted: September 26, 2023
• First Posted: October 13, 2023
• Study Start: May 19, 2023
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: April 3, 2025

Record last verified: 2025-03

Locations

US (1)