Effects of Ketone Ester Consumption on Exercise Tolerance and Cardiac Function

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

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).

Study Overview

• Status: Recruiting
• Conditions: Type 2 Diabetes; Ketone Body Metabolism; Ketones, Metabolism
• Intervention / Treatment: Dietary supplement: Ketone Ester Acute; Dietary supplement: Placebo Acute

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Debbie Scandling, BS; Phone Number: 614-688-5623; Email: debbie.scandling@osumc.edu
• Study Contact Backup: Name: Christopher Crabtree, MS; Email: crabtree.223@osu.edu

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • The Ross Heart Hospital
      • Contact: Debbie Scandling; Phone Number: 614-688-5623; Email: debbie.scandling@osumc.edu
      • Sub-Investigator: Orlando Simonetti, Ph.D.
      • Sub-Investigator: Jeff Volek, Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years old and ≤ 80 years old
2. Type II Diabetes Mellitus
3. Stable medical therapy for at least 1 months as determined by the treating physician (no plan to change between the two testing sessions)
4. Dose of oral diuretics changes allowed, but must be stable for 1 week prior to randomization
5. Body Mass Index (BMI) ≥ 25
6. Ability to participate in exercise treadmill testing (only if CPET is performed)
7. 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 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. 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
12. 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
13. Gastrointestinal surgery or gastrointestinal disorder that might interfere with supplement consumption. Prior bariatric surgery allowed if weight-stable for past 3 months.
14. 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)
15. Presence of any disease other than diabetes that results in a life expectancy of <1 year (in the opinion of the investigator)
16. Current enrolment in another investigational device or drug study or completion within <30 days of a trial of another investigational device or drug study.
17. 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
18. Any other clinical condition that might jeopardize subject safety during participation in this trial or prevent the subject from adhering to the trial Protocol.
19. Unable or unwilling to follow guidelines of assigned supplement group.
20. Allergy to test article ingredients, or lactose intolerance
21. The subject cannot currently be on a low-carb diet plan. 30-day washout would be required.
22. Refusal to consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Keto Ester Acute; This arm will provide a Ketone Ester supplement + a meal for consumption.	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 whole foods (i.e. chicken, rice, and a fruit bar) as a mix of macronutrients (29% protein, 3% fat, and 68% carbohydrate - not including the supplements). The meal consists of ~700kcal of food and will be standardized between all visits and subjects.
Placebo Comparator: Placebo Acute; This arm will provide a Placebo beverage + a meal for consumption.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cardiac MRI measures of cardiac function	Participants 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, 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 are added up and divided by the number of questions. A 7-point scale is used for areas where 1 is the best and 7 is the worst.	Baseline, 2 weeks
Metabolic Panel	Changes in metabolic blood panel will be assessed at lab visits.	Baseline, 2 weeks
Lipid Panel	Changes in lipid blood panel will be assessed at lab visits.	Baseline, 2 weeks
B-natriuretic peptide (BNP)	Changes in BNP (pg/mL) will be assessed at lab visits.	Baseline, 2 weeks
Change in Cardiac function after acute ingestion of KE or placebo	Cardiovascular performance and function will be investigated using CMR at rest, both before and immediately after consumption of KE or placebo.	Baseline, 2 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in fat storage	Participants undergo MRI scans, conducted by trained professionals. MRI imaging analyses will determine fat storage.	Baseline, 2 weeks

Collaborators and Investigators

• Sponsor: Ohio State University
• Investigators: Principal Investigator: Yuchi Han, MD, MMSc, Ohio State University

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2023
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: September 26, 2023
• First Submitted That Met QC Criteria: October 7, 2023
• First Posted (Actual): October 12, 2023

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Acid-Base Imbalance; Acidosis; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Ketosis
• Other Study ID Numbers: 2022H0376; CDMRP-PR212399-F (Other Grant/Funding Number: Departent of Defense)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No