Acute Effects of Oral Ketone Ester on Cardiac Function in Patients With COVID-19

Study Overview
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Brief Summary
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Based on Chinese studies, cardiac injury occurs in 20-30% of hospitalized patients and contributes to 40% of deaths. There are many possible mechanisms of cardiac injury in COVID-19 patients and increased myocardial oxygen demand and decreased myocardial oxygen supply are likely contributors to increased risk of myocardial infarction and heart failure. Interventions reducing the risk of cardiac injury are needed. Ketone bodies, such as 3-hydroxybutyrate and acetoacetate, can maintain ATP production in the heart and brain during starvation. It has been suggested that ketone bodies are more efficient substrates of energy metabolism than glucose, with a lower oxygen consumption per ATP-molecule produced. In addition, the reduction in hospitalizations due to heart failure observed in type 2 diabetes patients treated with sodium-glucose cotransporter 2 inhibitors, is suggested to be partly attributable to increased levels of 3-hydroxybutyrate. Infusion with 3-hydroxybutyrate reaching a plasma level of approximately 3 mM had acute beneficial hemodynamic effects in patients with heart failure and in healthy controls in a study by Nielsen et al. Improved haemodynamics and reduced systemic oxygen consumption might be of great benefit in patients with COVID-19. The primary endpoint is left ventricular ejection fraction. Secondary endpoints are conventional echocardiography parameters, peripheral blood oxygen saturation, venous blood oxygen saturation and urine creatinine clearance. The study population are twelve previously hospitalized patients with COVID-19 The study design is a randomized placebo-controlled double-blinded crossed-over acute intervention study.

Official Title
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Acute Effects of Oral Ketone Ester on Cardiac Function in Patients With COVID-19

Conditions
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COVID-19

Intervention / Treatment
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* Dietary Supplement: D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Patients previously hospitalized at hospitals of greater Copenhagen and the Zealand region with a laboratory confirmed diagnosis of COVID-19 > 18 years of age. Exclusion Criteria: Persons not able to cooperate Persons unable to understand and sign informed consent Diagnosis with chronic obstructive pulmonary disease Diagnosis with asthma Active treatment with sodium-glucose transporter 2 inhibitors eGFR < 15 ml/min/1.73m2 insulin-dependent diabetes

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized placebo-controlled double-blinded crossed-over acute intervention study.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester<br> | Dietary Supplement: D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester<br>* The intervention is D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester and will be bought commercially. As an example: One bottle of KetoneAid KE4 PRO with 60 ml contains 30 g D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester. For more information please refer to: https://shop.ketoneaid.com/collections/all/products/ke4-pro. Placebo will be a taste-matched water solution provided by the company. The placebo solution and the active solution will be prepared in identic bottles and investigators will be blinded.<br>|
| Placebo Comparator: Placebo<br> | Dietary Supplement: Placebo<br>* Taste-matched water<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left Ventricular ejection fraction | Echocardiography | 1 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global longitudinal strain | Echocardiography | 1 hour | 
| Cardiac output | Echocardiography | 1 hour | 
| Peripheral blood oxygen saturation | Pulse oximetry | 5 minutes | 
| Venous blood oxygen saturation | blood gas analysis | 5 minutes | 
| Urine creatinine clearance | Urine will be collected during the two cross-over sessions and urine creatinine will be measured on these two volumes. Creatinine clearance in ml/min/1.73m2 will then be estimated and compared with plasma creatinine for estimating kidney function. | 12 hours |