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Ketogenic Diet vs Mixed Diet in Patients With Heart Failure

Primary Purpose

Heart Failure With Preserved Ejection Fraction

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Ketogenic diet
Low-fat Mixed diet
Sponsored by
Ohio State University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Heart Failure With Preserved Ejection Fraction focused on measuring Ketogenic Diet, Heart Failure

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 ≥50% 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 and ≤ 50 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/1.73m2. Type I diabetes. History of diabetic ketoacidosis. Prior diagnosis of oxygen dependent pulmonary disease. Body Mass Index (BMI) < 25. 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.

Sites / Locations

  • The Ross Heart HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Ketogenic Diet

Low-fat mixed Diet

Arm Description

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.

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Change in Cardiac Output (L/min) via cardiovascular magnetic resonance imaging (CMR) .
Changes in cardiac output will be assessed via Cardiovascular magnetic resonance imagining conducted by trained professionals. MRI imaging analyses will determine cardiac function. The images will be analyzed by trained imaging professionals to determine overall change (L/min).
Change Stroke Volume(mL) via cardiovascular magnetic resonance imaging (CMR)
Changes in stroke volume will be assessed via Cardiovascular magnetic resonance imagining conducted by trained professionals. MRI imaging analyses will determine cardiac function. The images will be analyzed by trained imaging professionals to determine change in stroke volume (mL).
Percent change in ejection fraction via cardiovascular magnetic resonance imaging (CMR)
Percent changes in ejection fraction will be assessed via Cardiovascular magnetic resonance imagining conducted by trained professionals. MRI imaging analyses will determine cardiac function. The images will be analyzed by trained imaging professionals to determine change in Ejection Fraction(%).
Change in New York Heart Association (NYHA) class
NYHA class will be determined by clinical examination by a qualified cardiovascular physician
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.
Metabolic Panel
Changes in metabolic blood panel will be assessed at in lab visits (baseline, 6 weeks, and end of the study (26 weeks))
Lipid Panel
Changes in lipid blood panel will be assessed at in lab visits (baseline, 6 weeks, and end of the study (26 weeks))
B-natriuretic peptide (BNP)
Changes in BNP (pg/mL) will be assessed at in lab visits (baseline, 6 weeks, and end of the study (26 weeks)).
Continuous glucose/ketone monitor (CGM/CKM)
changes in daily glucose and ketone levels.

Full Information

First Posted
September 26, 2023
Last Updated
October 7, 2023
Sponsor
Ohio State University
Collaborators
United States Department of Defense
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1. Study Identification

Unique Protocol Identification Number
NCT06081543
Brief Title
Ketogenic Diet vs Mixed Diet in Patients With Heart Failure
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 19, 2023 (Actual)
Primary Completion Date
August 31, 2026 (Anticipated)
Study Completion Date
August 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ohio State University
Collaborators
United States Department of Defense

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
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. All participants will undergo the following tests on 2 separate visit days at these 3 testing time points during the study (baseline, 6 weeks, and end of the study (26 weeks) unless specified. These tests include: An in-person physical exam by one of the physician investigators. A Dual-energy X-ray absorptiometry (DXA) test, which is a test to measure your body composition. There is a small amount of radiation used in DXA, which is extremely low (by comparison, a standard chest x-ray is 125 times more radiation than a DXA scan). Two cardiac magnetic resonance imaging (MRI) scans. One consisting of non-contrast resting scans including elastography (MR safe drum-like device will generate mechanical waves on specific organs to test the stiffness of these organs) and another consisting of a contrast-enhanced MRI scan of the heart (The one with contrast will only be performed twice for the study, once at the baseline and once end of the study). A six-minute walk test (6MWT). You will walk along an even, undisturbed corridor for 6 minutes. A qualified person will supervise your test. The test has been used as a measure of exercise capacity in many patient populations and is extremely safe. A cardiopulmonary stress test (CPET), also know as an oxygen consumption test (VO2). During the CPET you will be asked to exercise on a treadmill or using an ergometer while breathing into a mask. This will be performed on a separate day from the 6MWT. Up to four tablespoons of blood will be drawn for a number of tests. 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. A 24-hour urine collection.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure With Preserved Ejection Fraction
Keywords
Ketogenic Diet, Heart Failure

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ketogenic Diet
Arm Type
Experimental
Arm Description
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.
Arm Title
Low-fat mixed Diet
Arm Type
Experimental
Arm Description
This arm will be provided food consisting of ~25% fat, and the remaining calories from carbohydrate (~55% after accounting for protein at ~20%).
Intervention Type
Dietary Supplement
Intervention Name(s)
Ketogenic diet
Intervention Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
Low-fat Mixed diet
Intervention Description
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.
Primary Outcome Measure Information:
Title
Changes in maximal exercise performance
Description
Participants will undergo VO2 max testing, conducted by trained professionals. VO2 max testing analyses will determine changes in maximal exercise performance
Time Frame
baseline, 6 weeks, and end of the study (26 weeks)
Secondary Outcome Measure Information:
Title
Change in Cardiac Output (L/min) via cardiovascular magnetic resonance imaging (CMR) .
Description
Changes in cardiac output will be assessed via Cardiovascular magnetic resonance imagining conducted by trained professionals. MRI imaging analyses will determine cardiac function. The images will be analyzed by trained imaging professionals to determine overall change (L/min).
Time Frame
baseline, 6 weeks, and end of the study (26 weeks)
Title
Change Stroke Volume(mL) via cardiovascular magnetic resonance imaging (CMR)
Description
Changes in stroke volume will be assessed via Cardiovascular magnetic resonance imagining conducted by trained professionals. MRI imaging analyses will determine cardiac function. The images will be analyzed by trained imaging professionals to determine change in stroke volume (mL).
Time Frame
baseline, 6 weeks, and end of the study (26 weeks)
Title
Percent change in ejection fraction via cardiovascular magnetic resonance imaging (CMR)
Description
Percent changes in ejection fraction will be assessed via Cardiovascular magnetic resonance imagining conducted by trained professionals. MRI imaging analyses will determine cardiac function. The images will be analyzed by trained imaging professionals to determine change in Ejection Fraction(%).
Time Frame
baseline, 6 weeks, and end of the study (26 weeks)
Title
Change in New York Heart Association (NYHA) class
Description
NYHA class will be determined by clinical examination by a qualified cardiovascular physician
Time Frame
baseline, 6 weeks, and end of the study (26 weeks)
Title
Change in Quality of Life Questionnaire
Description
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.
Time Frame
baseline, 6 weeks, and end of the study (26 weeks)
Title
Metabolic Panel
Description
Changes in metabolic blood panel will be assessed at in lab visits (baseline, 6 weeks, and end of the study (26 weeks))
Time Frame
baseline, 6 weeks, and end of the study (26 weeks)
Title
Lipid Panel
Description
Changes in lipid blood panel will be assessed at in lab visits (baseline, 6 weeks, and end of the study (26 weeks))
Time Frame
baseline, 6 weeks, and end of the study (26 weeks)
Title
B-natriuretic peptide (BNP)
Description
Changes in BNP (pg/mL) will be assessed at in lab visits (baseline, 6 weeks, and end of the study (26 weeks)).
Time Frame
baseline, 6 weeks, and end of the study (26 weeks)
Title
Continuous glucose/ketone monitor (CGM/CKM)
Description
changes in daily glucose and ketone levels.
Time Frame
Up to ~ 26 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 ≥50% 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 and ≤ 50 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/1.73m2. Type I diabetes. History of diabetic ketoacidosis. Prior diagnosis of oxygen dependent pulmonary disease. Body Mass Index (BMI) < 25. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Debbie Scandling, BS
Phone
614-688-5623
Email
debbie.scandling@osumc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Alyssa Marie Castillo, MS
Phone
614-688-1213
Email
alyssamarie.castillo@osumc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yuchi Han, MD, MMSc
Organizational Affiliation
Ohio State University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Ross Heart Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Debbie Scandling, BS
Phone
614-688-5623
Email
debbie.scandling@osumc.edu
First Name & Middle Initial & Last Name & Degree
Alyssa Marie Castillo, MS
Phone
614-688-1213
Email
alyssamarie.castillo@osumc.edu
First Name & Middle Initial & Last Name & Degree
Orlando Simonetti, Ph.D.
First Name & Middle Initial & Last Name & Degree
Jeff Volek, Ph.D.

12. IPD Sharing Statement

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Ketogenic Diet vs Mixed Diet in Patients With Heart Failure

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