NCT04573764: KetoCOVID

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

Completed NA Last updated 1 June 2022

What this trial tests

NA trial testing D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester in COVID-19 in 12 participants. Completed in 1 May 2022.

Timeline

1 February 2021

Primary endpoint
1 January 2022

1 May 2022

Quick facts

Lead sponsor	Steno Diabetes Center Copenhagen
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	triple
Primary purpose	treatment
Enrollment	12
Start date	1 February 2021
Primary completion	1 January 2022
Estimated completion	1 May 2022
Sites	1 location across Denmark

Drugs / interventions tested

• D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester
• Placebo

Conditions studied

• COVID-19 — all drugs for COVID-19 →

Sponsor

Steno Diabetes Center Copenhagen — full company profile →

Who can join

18 and older, any sex, with COVID-19. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. Regulated necrosis in COVID-19: A double-edged sword.
   Sun C, Han Y, Zhang R, Liu S, et al · · 2022 · cited 15× · PMID 36090995 · DOI 10.3389/fimmu.2022.917141
2. Oral ketone esters acutely improve myocardial contractility in post-hospitalized COVID-19 patients: A randomized placebo-controlled double-blind crossover study.
   Wodschow HZ, Davidovski FS, Christensen J, Lassen MCH, et al · · 2023 · cited 6× · PMID 36845050 · DOI 10.3389/fnut.2023.1131192
3. Developmental Impacts of Epigenetics and Metabolism in COVID-19.
   Naik N, Patel M, Sen R. · · 2024 · cited 5× · PMID 38390960 · DOI 10.3390/jdb12010009
4. Enhancing of cerebral Abeta clearance by modulation of ABC transporter expression: a review of experimental approaches.
   Loeffler DA. · · 2024 · cited 2× · PMID 38872626 · DOI 10.3389/fnagi.2024.1368200