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

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.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Dietary supplement: D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Please Select
    • Copenhagen, Please Select, Denmark, 2400
      • Bispebjerg Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Dietary supplement: Placebo; Taste-matched water
Active Comparator: D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester	Dietary supplement: D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Steno Diabetes Center Copenhagen
• Investigators: Principal Investigator: Tor Biering-Sørensen, MD, University of Copenhagen

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Actual): January 1, 2022
• Study Completion (Actual): May 1, 2022

Study Registration Dates

• First Submitted: October 1, 2020
• First Submitted That Met QC Criteria: October 1, 2020
• First Posted (Actual): October 5, 2020

Study Record Updates

• Last Update Posted (Actual): June 1, 2022
• Last Update Submitted That Met QC Criteria: May 30, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: H-20021500

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