Acute and Chronic Effects of Oral Ketones in Subjects With HFrEF and Diabetes
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Ketone Monoester (KE).
- Who it may be relevant to
- Registry conditions: Type 2 Diabetes, Heart Failure, Reduced Ejection Fraction. Basic parameters: 18 years — 80 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Overview
This study will provide insight into whether cardiac function changes with oral Ketone Esters (KE) administered to patients with Type 2 Diabetes Mellitus (T2DM) and Heart failure with reduced ejection fraction (HFrEF). Plasma ketones are avidly extracted by cardiac muscle and their uptake is not dependent upon insulin or influenced by insulin resistance.
Detailed description
After the screening visit, subject will take two separate doses of oral ketones during visit two. Subjects will have their first dose (400mg/kg) upon completion of the baseline Magnetic Resonance Imaging (MRI), and then a second dose (400mg/kg) approximately 1.5 hours after their consumption of the 1st dose. Approximately 1.5 hours after their second dose (3hr since first dose), the subject will undergo a second cardiac MRI. Baseline Blood samples of Beta-hydroxybutyrate (BOHB), acetoacetate (ACAC), Free Fatty Acids (FFA), insulin, c-peptide, glucagon, and an additional 10ml (for storage and later analysis) will be drawn prior to their first dose, then every 30 minutes after their first dose, until completion of the second MRI, then a final blood draw upon completion of the MRI for a total of 8 blood draws during visit 2. An IV catheter will be placed into one antecubital vein by a study nurse for all blood draws during visit 2.
The subject will then be asked to return to complete a third MRI approximately 24 hours after their second MRI. Blood samples for BOHB, acetoacetate (ACAC), insulin, c-peptide and glucagon, and an additional 10 ml will be drawn prior to their third MRI. An IV catheter will be placed into one antecubital vein by a study nurse for all blood draws during visit 3.
After completion of the third MRI, subjects will be dosed KE 400mg/kg once daily until the visit 4 MRI can be completed.
Blood samples for BOHB, acetoacetate (ACAC), insulin, c-peptide, glucagon, proBNP, and an additional 10 ml will be drawn prior to their fourth MRI. An IV catheter will be placed into one antecubital vein by a study nurse for all blood draws during visit 4. The 4th MRI, based on subject and scanner availability at approximately Day 7
Interventions
- Drug Ketone Monoester (KE)
Ketones are a nutritional supplement currently used by athletes for their performance enhancing effects - specifically their cardio-pulmonary benefits
Primary outcome measures
- Cardiac Efficiency after acute dose (Left-ventricular function) [Time frame: 1.5 hours to 24 hours]
- Cardiac Efficiency after chronic dosing (Left-ventricular function) [Time frame: 1.5 hours to 7 days]
Secondary outcome measures (8)
- Six minute walk test [Time frame: Baseline to 7 days]
- Acetoacetate [Time frame: Baseline to 7 days]
- Glucose [Time frame: Baseline to 7 days]
- Free Fatty Acids (FFAs) [Time frame: Baseline to 7 days]
- Insulin/C-peptide [Time frame: Baseline to 7 days]
- Glucagon [Time frame: Baseline to 7 days]
- Beta-hydroxybutyrate [Time frame: Baseline to 7 days]
- Patient Reported Outcomes Measure Information System (PROMIS) - Physical Function [Time frame: Baseline to 7 days]
Eligibility criteria
Inclusion criteria
- Subjects must be on a stable dose of guideline-directed medications for Heart Failure (HF).
- Patients will have an established diagnosis of HF before the screening visit, documented by an acceptable imaging modality in the last 6 months.
- Age = 18-80 y
- Body Mass Index (BMI) =23-38 kg/m2
- Glycated hemoglobin (HbA1c) = 6.0-10.0%
- Blood Pressure (BP) < 145/85 mmHg
- Estimated Glomerular Filtration Rate (eGFR) > 30 ml/min•1.73 m2
- For women of child-bearing age (WOCBA) willingness to use contraception, if applicable.
Exclusion criteria
- Patients treated with Sodium-Glucose Transport Protein (SGLT2i's) or medications that may impair heart function or acutely worsen glycemic control will be excluded.
- Pregnancy, lactation, or plans to become pregnant. A negative pregnancy test will be performed before each Magnetic resonance imaging (MRI) study to assess current status.
- Allergy/sensitivity to study drugs or their ingredients.
- Current drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- Inability or unwillingness of individual or legal guardian/representative to give written informed consent.
- Subjects with a history of cancer (except basal or squamous cell cancer that has been resolved/remission for 5 years)
- Cardiovascular event within the last 3 months
- Major organ or metabolic diseases, or physical limitations that will not allow the subject to complete the study.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 1 center
- University of Texas Health Science Center at San Antonio — San Antonio
Identifiers
NCT: NCT06108076 · 20230420HU · 1UM1TR004538-01