COVID-19KetoCOVIDNCT04573764
Acute Effects of Oral Ketone Ester on Cardiac Function in Patients With COVID-19
A study testing D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester in people with COVID-19, run by Steno Diabetes Center Copenhagen at 1 site in Denmark.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19
- What is being tested?
- D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Feb 2021to 1 May 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients previously hospitalized at hospitals of greater Copenhagen and the Zealand region with a laboratory confirmed diagnosis of COVID-19 > 18 years of age.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read more
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
- Being tested
- D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester, Placebo
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
D-beta-hydroxybutyrate-(R)-1,3 butanediol monoesterDietary 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.
PlaceboDietary supplement
Taste-matched water
| Study group | Role | What they receive |
|---|---|---|
| D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester | Active comparator | Not described Receives: Dietary Supplement: D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester |
| Placebo | Placebo comparator | Not described Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Left Ventricular ejection fraction
Echocardiography
Measured: 1 hour
Secondary outcomes (5)
Global longitudinal strain
Echocardiography
Measured: 1 hour
Cardiac output
Echocardiography
Measured: 1 hour
Peripheral blood oxygen saturation
Pulse oximetry
Measured: 5 minutes
Venous blood oxygen saturation
blood gas analysis
Measured: 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.
Measured: 12 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2020
- Study start1 Feb 2021
- Primary completion1 Jan 2022
- Study completion1 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized placebo-controlled double-blinded crossed-over acute intervention study.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Steno Diabetes Center Copenhagen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tor Biering-Sørensen, MD, Principal investigator, University of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04573764
- Sponsor's protocol ID
- H-20021500
- Acronym
- KetoCOVID
- Status last verified
- May 2022
- First submitted
- 1 Oct 2020
- Last updated
- 1 Jun 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute Effects of Oral Ketone Ester on Cardiac Function in Patients With COVID-19
- ClinicalTrials.gov ID
- NCT04573764
- Acronym / sponsor ID
- KetoCOVID / H-20021500
- Conditions
- COVID-19
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Steno Diabetes Center CopenhagenUniversity, hospital or other
- Study start
- 1 Feb 2021 (actual)
- Primary completion
- 1 Jan 2022 (actual)
- Study completion
- 1 May 2022 (actual)
- First posted
- 5 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Randomized placebo-controlled double-blinded crossed-over acute intervention study.
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients previously hospitalized at hospitals of greater Copenhagen and the Zealand region with a laboratory confirmed diagnosis of COVID-19 > 18 years of age.
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| D-beta-hydroxybutyrate-(R)-1,3 butanediol monoesterThe 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. | Dietary supplement | D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester |
| PlaceboTaste-matched water | Dietary supplement | Placebo |
Primary outcome
Left Ventricular ejection fraction
Time frame: 1 hour
Echocardiography
5 secondary outcomes
Global longitudinal strain
Time frame: 1 hour
Cardiac output
Time frame: 1 hour
Peripheral blood oxygen saturation
Time frame: 5 minutes
Venous blood oxygen saturation
Time frame: 5 minutes
Urine creatinine clearance
Time frame: 12 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tor Biering-Sørensen, MD principal investigator
University of Copenhagen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester in people with COVID-19, run by Steno Diabetes Center Copenhagen at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Left Ventricular ejection fraction (time frame: 1 hour). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2022.