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

• ClinicalTrials.gov Identifier: NCT04573764
• Recruitment Status: Completed
• First Posted: October 5, 2020
• Last Update Posted: June 1, 2022
• Sponsor: Steno Diabetes Center Copenhagen
• Information provided by (Responsible Party): Steno Diabetes Center Copenhagen

Study Description

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.

Condition or disease	Intervention/treatment	Phase
COVID-19	Dietary Supplement: D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester; Dietary Supplement: Placebo	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Randomized placebo-controlled double-blinded crossed-over acute intervention study.
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Acute Effects of Oral Ketone Ester on Cardiac Function in Patients With COVID-19
• Actual Study Start Date: February 1, 2021
• Actual Primary Completion Date: January 1, 2022
• Actual Study Completion Date: May 1, 2022

Arms and Interventions

Arm	Intervention/treatment
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.
Placebo Comparator: Placebo	Dietary Supplement: Placebo; Taste-matched water

Outcome Measures

Primary Outcome Measures :

1. Left Ventricular ejection fraction [ Time Frame: 1 hour ]
   Echocardiography

Secondary Outcome Measures :

1. Global longitudinal strain [ Time Frame: 1 hour ]
   Echocardiography
2. Cardiac output [ Time Frame: 1 hour ]
   Echocardiography
3. Peripheral blood oxygen saturation [ Time Frame: 5 minutes ]
   Pulse oximetry
4. Venous blood oxygen saturation [ Time Frame: 5 minutes ]
   blood gas analysis
5. Urine creatinine clearance [ Time Frame: 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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Denmark

Bispebjerg Hospital

Copenhagen, Please Select, Denmark, 2400

Sponsors and Collaborators

Steno Diabetes Center Copenhagen

Investigators

• Principal Investigator: Tor Biering-Sørensen, MD; University of Copenhagen

More Information

• Responsible Party: Steno Diabetes Center Copenhagen
• ClinicalTrials.gov Identifier: NCT04573764
• Other Study ID Numbers: H-20021500
• First Posted: October 5, 2020
• Last Update Posted: June 1, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

COVID-19; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases