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

Not Applicable

Completed

• Conditions: COVID-19
• Interventions: Dietary Supplement: D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester; Dietary Supplement: Placebo

• Registration Number: NCT04573764
• Lead Sponsor: Steno Diabetes Center Copenhagen

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-10-01
• Study First Submitted QC: 2020-10-01
• Study First Posted: 2020-10-05
• Study Start: 2021-02-01
• Primary Completion: 2022-01-01
• Status Verified: 2022-05
• Study Completion: 2022-05-01
• Last Update Submitted: 2022-05-30
• Last Update Posted: 2022-06-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester	D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Left Ventricular ejection fraction	1 hour	Echocardiography

Secondary Outcome Measures

Name	Time	Method
Peripheral blood oxygen saturation	5 minutes	Pulse oximetry
Venous blood oxygen saturation	5 minutes	blood gas analysis
Cardiac output	1 hour	Echocardiography
Global longitudinal strain	1 hour	Echocardiography
Urine creatinine clearance	12 hours	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.

Trial Locations

Locations (1)

Bispebjerg Hospital; 🇩🇰 Copenhagen, Please Select, Denmark