Effects of Ketone Ester Consumption on Exercise Tolerance and Cardiac Function

Official title

Effects of Acute and Chronic Ketone Ester Consumption on Exercise Tolerance and Cardiac Function in Subjects With Diabetes

Overview

This study is being done to evaluate how a ketone ester (KE) supplement affects heart function and health in people with diabetes compared to a placebo supplement (made with standard food ingredients that do not contain ketone esters).

Detailed description

This study is a single center, randomized controlled study of up to 30 subjects with diabetes. The study is designed to compare the acute effects of KE versus an energy and volume matched placebo on cardiac function and blood flow following a meal. Eligible subjects will have a known diagnosis of type 2 diabetes and will be selected from a larger population at the Ohio State University Wexner Medical Center. Enrolled subjects will be stratified by sex to ensure equal proportions of men and women in each group (KE and placebo) and then randomly assigned (1:1) to a group, before washing out and crossing over to the other group (KE or Placebo). The order of treatment will be randomized such that half the cohort starts first with KE, and the other half with Placebo.

CMR will be performed on the days of supplement ingestion. CPET may be performed prior to starting the first intervention. Following a 2-wk washout period, each patient will replicate the acute CMR visit with the opposing treatment (KE or Placebo).

CMR will be used to evaluate cardiac function, myocardial blood flow, and cardiac and vascular function. CMR will provide insightful data on the magnitude, timeline, and functional impact of nutritional ketosis on cardiovascular function and myocardial blood flow in patients diagnosed with T2D.

Interventions

• Dietary supplement Ketone Ester Acute
  Participants will undertake a controlled feeding intervention where they will consume 25g of C8 Ketone Diester with a meal, and images obtained before and after consumption. The supplement powder contains 12.5 g C8 Diester, sodium caseinate and soluble corn fiber, per serving. The powder contains 120 kcal, 0 g fat, 3 g carbohydrate, and 0 g protein. A standardized meal will be provided to subjects to consume with their allocated supplement during the MRI visits. This meal is formulated with who
• Dietary supplement Placebo Acute
  Participants will undertake a controlled feeding intervention where they will drink two servings of the placebo with a meal, and images obtained before and after consumption. The placebo is flavor, energy, volume, and macronutrient matched will be given to patients as part of the placebo arm of the study. This placebo will not contain any BHB, which will be replaced with a similar caloric content of fat in the form of canola oil.

Primary outcome measures

• Change in Cardiac MRI measures of cardiac function [Time frame: Baseline, 2 weeks]

Secondary outcome measures (5)

• Change in Quality of Life Questionnaire [Time frame: Baseline, 2 weeks]
• Metabolic Panel [Time frame: Baseline, 2 weeks]
• Lipid Panel [Time frame: Baseline, 2 weeks]
• B-natriuretic peptide (BNP) [Time frame: Baseline, 2 weeks]
• Change in Cardiac function after acute ingestion of KE or placebo [Time frame: Baseline, 2 weeks]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years old and ≤ 80 years old
• Type II Diabetes Mellitus
• Stable medical therapy for at least 1 months as determined by the treating physician (no plan to change between the two testing sessions)
• Dose of oral diuretics changes allowed, but must be stable for 1 week prior to randomization
• Body Mass Index (BMI) ≥ 25
• Ability to participate in exercise treadmill testing (only if CPET is performed)
• Ability to sign written consent

Exclusion criteria

• Women who are pregnant, current breast-feeding, or have intention to become pregnant while in the trial
• 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 with 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
• 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 supplement consumption. 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 diabetes that results in a life expectancy of <1 year (in the opinion of the investigator)
• Current enrolment in another investigational device or drug study or completion within <30 days of a trial of another 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 fulfil the trial requirements or complete the trial
• Any other clinical condition that might jeopardize subject safety during participation in this trial or prevent the subject from adhering to the trial Protocol.
• Unable or unwilling to follow guidelines of assigned supplement group.
• Allergy to test article ingredients, or lactose intolerance
• The subject cannot currently be on a low-carb diet plan. 30-day washout would be required.
• Refusal to consent

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Triple blind

Primary purpose

Basic science

Study locations

United States · 1 center

• The Ross Heart Hospital — Columbus

Identifiers

NCT: NCT06078683 · 2022H0376 · CDMRP-PR212399-F

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗