Effects of Ketone Ester Consumption on Exercise Tolerance and Cardiac Function

Launched by OHIO STATE UNIVERSITY · Oct 7, 2023

Keywords

ClinConnect Summary

This clinical trial is studying the effects of a special drink called a ketone ester (KE) on heart function and exercise ability in people with certain health conditions, such as heart failure, type 2 diabetes, or metabolic syndrome. Participants will compare the ketone ester drink to a placebo drink, which is made from regular food ingredients and does not contain the ketone ester. The goal is to see if the ketone ester can help improve heart health and overall fitness.

To join the trial, participants must be between 18 and 80 years old, have a specific type of heart failure (known as heart failure with preserved ejection fraction), and meet other health criteria, such as having stable medical treatment for their conditions. Participants can expect to take the drink and take part in exercise tests to measure how well their heart and body respond. It’s important to note that those with certain medical conditions, recent surgeries, or specific heart devices may not be eligible for the trial. If you're interested and think you might qualify, this could be an opportunity to help researchers learn more about heart health and potentially find new treatments.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• Inclusion Criteria:
• • 1. Age ≥ 18 years old and ≤ 80 years old
• • 2. NYHA class I - III for at least 3 months
• • 3. Ejection fraction ≥ 50% by biplane 2D echo, 3D echo, or CMR.
• • 4. Echo findings of abnormal of indeterminant diastolic function or Right 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). Dose down titration and discontinuation is allowed during the study
• • 6. Dose of oral diuretics changes allowed, but must be stable for 1 week prior to randomization
• • 7. Body Mass Index (BMI) ≥ 25 and ≤ 50 or Type II Diabetes Mellitus or prediabetes as defined by fasting glucose of 100 - 125 mg/dL or glycated hemoglobin (A1C) 5.7-6.4%, or metabolic syndrome
• • a. To meet definition of metabolic syndrome (NCEP ATPIII), 3 of the following criteria must be met: i. Abdominal obesity, defined as a waist circumference ≥102 cm (40 in) in men and ≥88 cm (35 in) in females ii. Serum triglycerides ≥150 mg/dL (1.7 mmol/L) or drug treatment for elevated triglycerides iii. Serum high-density lipoprotein (HDL) cholesterol \<40 mg/dL (1 mmol/L) in males and \<50 mg/dL (1.3 mmol/L) in females or drug treatment for low HDL cholesterol iv. Blood pressure ≥130/85 mmHg or drug treatment for elevated blood pressure v. Fasting plasma glucose (FPG) ≥100 mg/dL (5.6 mmol/L) or drug treatment for elevated blood glucose
• • 8. Ability to participate in exercise treadmill testing
• • 9. Ability to sign written consent
• Exclusion Criteria:
• • 1. Women who are pregnant, current breast-feeding, or have intention to become pregnant while in the trial
• • 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 with estimated glomerular filtration rate (eGFR) \<30 ml/kg/1.73m2
• • 7. Type I diabetes
• • 8. History of diabetic ketoacidosis
• • 9. Prescription use of sodium-glucose cotransporter-2 inhibitors (SGLT2i)
• • 10. Prior diagnosis of oxygen dependent pulmonary disease
• • 11. Body Mass Index (BMI) \< 25
• • 12. Recent acute myocardial infarction or acute coronary syndrome (30 days)
• • 13. Recent (within 30 days) or planned (within 30 days) cardiac revascularization.
• • 14. History of un-revascularized left main coronary artery disease, severe un- revascularized triple vessel disease, coronary artery bypass graft surgery \< 30 days.
• • 15. Left ventricular ejection fraction \< 50%
• • 16. Uncontrolled systemic systolic/diastolic blood pressure (SBP/DBP) hypertension (SBP \>180 or DBP \>110 mmHg)
• • 17. Severe stenotic or regurgitant valvular heart disease, expected to lead to surgery during the trial period.
• • 18. Persistent atrial fibrillation.
• • 19. History of uncontrolled or untreated ventricular arrhythmias
• • 20. Cardiovascular diseases or treatments that increase the unpredictability of the subject's clinical course, independent of heart failure
• • 21. Heart transplant or listing for heart transplant.
• • 22. 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
• • 23. 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
• • 24. Hemoglobin of \<9 g/dL at screening
• • 25. 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
• • 26. 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
• • 27. Gastrointestinal surgery or gastrointestinal disorder that might interfere with supplement consumption. Prior bariatric surgery allowed if weight-stable for past 3 months.
• • 28. 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)
• • 29. Presence of any disease other than heart failure that results in a life expectancy of \<1 year (in the opinion of the investigator)
• • 30. History or recurrent severe hypokalemia, potassium \< 3.0 mg/dL.
• • 31. Current enrolment in another investigational device or drug study or completion within \<30 days of a trial of another investigational device or drug study.
• • 32. Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, will make the subject unlikely to fulfil the trial requirements or complete the trial
• • 33. Any other clinical condition that might jeopardize subject safety during participation in this trial or prevent the subject from adhering to the trial Protocol.
• • 34. Unable or unwilling to follow guidelines of assigned supplement group.
• • 35. Allergy to test article ingredients, or lactose intolerance
• • 36. The subject cannot currently be on a low-carb diet plan. 30-day washout would be required.
• • 37. Patient must 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.
• • 38. Refusal to consent