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

NCT04573764 | Completed DMC

• 1 other identifier: H-20021500
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

COVID-19

Outcome Measures

Primary Outcomes (1)

• Left Ventricular ejection fraction

  Echocardiography

  1 hour

Secondary Outcomes (5)

• Global longitudinal strain

  1 hour

• Cardiac output

  1 hour

• Peripheral blood oxygen saturation

  5 minutes

• Venous blood oxygen saturation

  5 minutes

• Urine creatinine clearance

  12 hours

Study Arms (2)

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

ACTIVE COMPARATOR

Dietary Supplement: D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester

Placebo

PLACEBO COMPARATOR

Dietary Supplement: Placebo

Interventions

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

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.

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

Placebo DIETARY_SUPPLEMENT

Taste-matched water

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Patients previously hospitalized at hospitals of greater Copenhagen and the Zealand region with a laboratory confirmed diagnosis of COVID-19 \> 18 years of age.

You may not qualify if:

• 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

Sponsors & Collaborators

• Steno Diabetes Center Copenhagen: lead

Study Sites (1)

Bispebjerg Hospital

Copenhagen, Please Select, 2400, Denmark

Location

MeSH Terms

Conditions

COVID-19

Interventions

beta-hydroxybutyrate-1,3-butanediol monoester

Condition Hierarchy (Ancestors)

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

Study Officials

• Tor Biering-Sørensen, MD

  University of Copenhagen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized placebo-controlled double-blinded crossed-over acute intervention study.

Study Record Dates

• First Submitted: October 1, 2020
• First Posted: October 5, 2020
• Study Start: February 1, 2021
• Primary Completion: January 1, 2022
• Study Completion: May 1, 2022
• Last Updated: June 1, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)