Ketone Pharmacokinetic Study in HFrEF

Study Overview
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Brief Summary
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The purpose of this study is to test whether an over-the-counter ketone ester drink is well tolerated in people with heart failure on, and not on, a heart failure medication class called SGLT2 inhibitors. The research team is trying to determine the safest dose of Delta G. The study has a single visit. Participants will be served a light breakfast with the study drink, a physical exam will be conducted, and the study team will obtain information about demographics and medical history. The study team will draw blood intravenously up to eight times over the course of the half-day visit.

Official Title
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Ketone Pharmacokinetic Study in Heart Failure With Reduced Ejection Fraction

Conditions
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Heart Failure With Reduced Ejection Fraction

Intervention / Treatment
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* Dietary Supplement: DeltaG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of HFrEF (ejection fraction<=45%) Systolic blood pressure greater >=90 mmHg Exclusion Criteria: Intentional ketogenic (high fat, low carbohydrate) diet (must be off ketogenic diet for >7 days prior to visit) Significant liver disease (cirrhosis) or alcohol abuse disorder (>14 drinks/week). Unique cardiomyopathies: infiltrative/hypertrophic cardiomyopathy, pericardial disease, or other cardiomyopathies that in the investigator's opinion have unique treatment options that would be less likely to be affected by ketone therapy. Estimated glomerular filtration rate<25 mL/min/1.73 m2 as the most recent value in the last year. Type 1 diabetes mellitus Use of ventricular assist device, history of heart transplant, or use of continuous inotropes Pregnant women. Due to unknown affects of nutritional ketosis in pregnant women, pregnancy will be an exclusion. Accordingly, women of childbearing age with a menstrual cycle within the past year will be asked to submit a urine specimen for pregnancy testing.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: Participants stratified based on use of background use of SGLT2 inhibitors
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketone ester<br>All patients will receive ketone ester as (R)-3-hydroxybutyl (R)-3-hydroxybutyrate. This will begin at 250 mg/kg once with dose escalation to 500 mg/kg in subsequent participants if all safety endpoints are achieved among 5 consecutive participants. | Dietary Supplement: DeltaG<br>* (R)-3-hydroxybutyl (R)-3-hydroxybutyrate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Venous pH | Peripheral blood | 1 hour | 
| Glucose | Peripheral blood | 1 hour | 
| Systolic blood pressure | Taken by blood pressure cuff on the arm | 1 hour | 
| Beta-hydroxybutyrate level | Peripheral blood | 1 hour | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DeltaG, ketone ester, metabolites, metabolomics, ketoacidosis