Ketogenic Diet in Patients With Heart Failure

Benefits of Ketogenic Diet in Patients With Heart Failure With Preserved Ejection Fraction: A Pilot Study

This study is being done to evaluate the effects of a low carbohydrate ketogenic diet on exercise tolerance in patients with Heart Failure with Preserved Ejection Fraction (HFpEF), also known as Diastolic Heart Failure (DHF).

Study Overview

• Status: Terminated
• Conditions: Heart Failure With Preserved Ejection Fraction
• Intervention / Treatment: Other: Nutritional and Dietary Manipulation

Detailed Description

Patients will be randomized to either a ketogenic diet, or a low-fat diet higher in carbohydrate and based on current dietary guidelines. Regardless of what group you are randomized to, you will consume the diet for a period of 4 weeks. All foods will be prepared by our research group and provided to you. Both diets will be based on an approximately 25% reduction in your dietary caloric requirements, so some weight loss may occur over the 4-week intervention.

Primary data collection will occur at baseline and at four weeks, with more frequent monitoring of blood markers, blood pressure, heart rate, and overall health. Throughout the duration of the study, you will be continued on standard heart failure therapies as guided by your treating physician. The duration of the study is expected to last for approximately 6 weeks. This includes all before and after testing, as well as the 4 weeks on diet.

All patients will undergo a resting MRI scan of the heart at enrollment (baseline), and again at the end of the 4-week diet. You will not receive any injections.

All participants will also undergo a cardiopulmonary stress test (CPET, also known as VO2 testing) at enrollment (baseline) and again at the end of the 4-week dietary intervention. During the Cardiopulmonary stress testing you will be asked to exercise on a treadmill while breathing into a mask.

All participants will also undergo body fat and body fluid composition by dual-energy X-ray absorptiometry (DXA) at enrollment (baseline) and again at the end of the 4 week dietary intervention. You will be exposed to a very small amount of radiation by the DXA scanner used to measure your body composition. However, amount of radiation used in DXA is extremely low (by comparison, a standard chest x-ray is 125 times more radiation than a DXA scan).

Blood tests will be performed at enrollment (baseline) and again at the end of the 4 week dietary intervention. Blood draws may cause discomfort at the skin puncture site and a small bruise may develop that may persist for several weeks. There is also a small possibility of an infection. These risks are identical to standard clinical blood draws.

After 2-weeks, and again after 4 weeks on diet, all participants will undergo a clinical examination by a cardiologist.

All participants will be provided with a handheld glucometer and test strips to check ketone levels daily in the morning after an overnight fast. This requires a finger prick to obtain the drop of blood required for the test. The finger stick may cause a slight immediate discomfort at the specific stick site. Subjects will also be required to check and record ketones 4x/day on one day per week to capture a more accurate record of ketone levels during waking hours. You will bring the glucometer readings with you when you pick up food so that the results can be downloaded and recorded by a member of the research team.

Patients on either diet will personally pick up food 3X per week. Patients will weigh-in and have their heart rate and blood pressure checked at the time of each food pick up. The MRI, the cardiopulmonary stress test and all blood testing will be done at the Ross Heart Hospital or the Davis Heart and Lung Research Institute. The DXA testing, as well as the food pickup will be done at the Physical Activity and Educational Services (PAES) building on The Ohio State University campus.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years old and ≤ 75 years old & willingness to be randomized to either diet
• Confirmed diagnosis of heart failure with ejection fraction ≥50% (NYHA Class II-IV)
• On optimal medical therapy for at least 3 months as determined by the treating physician
• Body Mass Index (BMI) ≥ 25
• Ability to participate in exercise treadmill testing

Exclusion Criteria:

• Contraindications to MRI including pregnancy
• Diagnosis of diabetes mellitus treated with insulin or SGLT2 inhibitors.
• History of diabetic ketoacidosis
• Recent (within 30 days) or planned (within 30 days) cardiac revascularization
• Recent acute myocardial infarction or acute coronary syndrome (30 days)
• Body Mass Index (BMI) < 25, or BMI > 40
• Hepatic cirrhosis
• Use of metformin > 1700 mg daily
• Left ventricular ejection fractions < 50%
• Prior diagnosis of moderate to severe COPD
• Uncontrolled systemic systolic/diastolic hypertension (SBP > 150 mmHg or DBP > 90 mmHg)
• Echocardiographic evidence of significant valvular disease
• History of ventricular tachycardia or SCD
• Untreated moderate or severe sleep apnea

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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%).	Other: Nutritional and Dietary Manipulation; Participants will undertake a controlled feeding intervention. All food will be prepared and delivered to participants by research staff. Participants will be asked to exclusively eat what is provided to them in efforts to control any dietary effects.
Experimental: Ketogenic Diet; This arm will be provided food to induce a state of nutritional ketosis in each person as defined as blood [3-OHB] ≥0.5 mM.	Other: Nutritional and Dietary Manipulation; Participants will undertake a controlled feeding intervention. All food will be prepared and delivered to participants by research staff. Participants will be asked to exclusively eat what is provided to them in efforts to control any dietary effects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 and end of study participation, 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in CMR measures of cardiac function	Participants will undergo MRI scans, conducted by trained professionals. MRI imaging analyses will determine cardiac function. The images will be analyzed by trained imaging professionals to determine overall change in cardiac function.	Baseline and end of study participation, 6 weeks
Change in NYHA class	NYHA class will be determined by clinical examination by a qualified cardiovascular physician	Baseline and end of study participation, 6 weeks
Change in Quality of Life Questionnaire	Participants will complete a quality of life questionnaire several times throughout the study. The questions are divided into three areas: Dyspnea, Fatigue and Emotional Function. The scores for each area are added up and divided by the number of questions. A 7-point scale is used for all areas where 1 is the best and 7 is the worst.	Baseline and end of study participation, 6 weeks
Change in Serologic Markers	Cardio-metabolic risk markers will be determined through blood samples taken throughout the study. We will look at B-natriuretic peptide (BNP), total cholesterol, HDL, LDL, triglycerides, lipoprotein particle distribution, fasting blood glucose, serum potassium, sodium, and magnesium.	Baseline and end of study participation, 6 weeks

Collaborators and Investigators

• Sponsor: Ohio State University
• Investigators: Principal Investigator: Sitaramesh Emani, MD, The Ohio State University Wexner Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2019
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: January 15, 2020
• First Submitted That Met QC Criteria: January 16, 2020
• First Posted (Actual): January 22, 2020

Study Record Updates

• Last Update Posted (Actual): July 24, 2024
• Last Update Submitted That Met QC Criteria: July 22, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: 2019H0255

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Final results will be published via peer-review process.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No