Heart FailurePhase 2KETO-KINETICS1NCT04443426
Modulation of Circulating Levels of the Ketone Body 3-hydroxybutyrate in Patients With Chronic Heart Failure: Cardiovascular Effects
A Phase 2 study testing Oral 3-hydroxybutyrate salts and Ketone Monoester in people with Heart Failure and Ketosis, run by University of Aarhus at 1 site in Denmark.
Trial summary
The ketone body 3-hydroxybutyrate (3-OHB) is a naturally occurring energy substrate, and is associated with increased life span and improved health. We have previously shown that intravenous 3-OHB treatment increases myocardial blood flow > 70% in healthy humans and data from our group show that 3-OHB increases… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Ketosis, Ketonemia
- What is being tested?
- Oral 3-hydroxybutyrate salts and Ketone Monoester
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 1 siteDenmark
- Study dates
- 25 Apr 2019to 1 Nov 2022
- Phase
- Phase 2
- 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
- Chronic Heart Failure;
- NYHA class II-III
- Left Ventricular Ejection Fraction <40%
Who cannot join
- Diabetes or HbA1c > 48 mmol/mol
- Significant cardiac valve disease,
- Severe stable angina pectoris
- Severe comorbidity as judged by investigator,
- Inability to give informed consent.
Trial locations and contacts
1 site in 1 country.
About this study
The ketone body 3-hydroxybutyrate (3-OHB) is a naturally occurring energy substrate, and is associated with increased life span and improved health. We have previously shown that intravenous 3-OHB treatment increases myocardial blood flow > 70% in healthy humans and data from our group show that 3-OHB increases cardiac output by 40 % in patients with heart failure.
In this study the investigators aim to investigate:
- If this effect is reproducible with a commercially available oral ketone supplements
- The safety of commercially available ketone supplements in heart failure patients
Read the detailed description
Heart Failure (HF) is a major public health issue because the disease affects 1-2% of the Western population and the lifetime risk of HF is 20%. HF is responsible for 1-2% of all healthcare expenditures. Despite major improvements in the management and care of patients with HF, the 1-year mortality in patients with HF is 13 % and >50% of HF-patients is admitted during a 2.5 year period. Furthermore patients with HF have markedly decreased physical capacity and quality of life. Thus, there is a need for new treatment modalities in this group of patients.
Ketone bodies are produced in the liver and are of vital importance in the human body for energy generation in the heart and brain during fasting, exercise and severe illness. Ketosis can be safely obtained using dietary supplements and can increase exercise capacity in athletes. The most important ketone bodies are 3-hydroxybutyrate (3-OHB) and acetoacetate. Recently, it was demonstrated that patients with severe HF have increased myocardial utilization of the ketone body 3-hydroxybutyrate.
We have shown, using positron emission tomography, that ketone body infusion reduces myocardial glucose uptake and increases myocardial blood flow in healthy subjects. Data from another study conducted by our group show a 40% increase in cardiac output during infusion of 3-OHB.
Presently there are no data on the clinical cardiovascular and metabolic effects of long-term oral ketone-supplementation in patients with chronic HF.
In this study the investigators will whether ketosis obtained by oral ketone supplements affects hemodynamics and contractile function.
- Conditions
- Heart Failure, Ketosis, Ketonemia
- Being tested
- Oral 3-hydroxybutyrate salts, Carbohydrate Placebo, Ketone Monoester
- Keywords
- Metabolism
- Medical subject headings
- Heart Failure, Ketosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral 3-hydroxybutyrate saltsDietary supplement
Comercially available 3-hydroxybutyrate salts with 36 grams of 3-OHB salts three times daily.
Carbohydrate PlaceboDietary supplement
Comercially available carbohydrate sports drink. The placebo dose is isocaloric to the 3-hydroxy butyrate dose.
Ketone MonoesterDietary supplement
Commercially available ketone monoester in a dosage isocaloric to 3-OHB salts.
| Study group | Role | What they receive |
|---|---|---|
| Single dose oral 3-hydroxybutyrate monoester | Experimental | Cross-over study in 8 patients receiving single-dose oral 3-hydroxybutyrate monoester, 3-OHB salt and placebo. Receives: Dietary Supplement: Ketone Monoester |
| Single dose oral 3-hydroxybutyrate Salt | Experimental | Not described Receives: Dietary Supplement: Oral 3-hydroxybutyrate salts |
| Single dose oral placebo | Placebo comparator | maltodextrin-based, isocaloric to ketone dosis. Receives: Dietary Supplement: Carbohydrate Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiac Output (L/min)
Right Heart Catherization
Measured: 5 hours - Area under the curve
Secondary outcomes (2)
Left Ventricle Ejection Fraction (%)
Echocardiography
Measured: 5 Hours - Area under the curve
Left Ventricular filling pressure (mmHg)
Right Heart Catherization
Measured: 5 hours - Area under the curve
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2020
- Study start25 Apr 2019
- Primary completion1 Nov 2022 (estimated)
- Study completion1 Nov 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by University of AarhusThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kristian H Christensen, MD, Principal investigator, Aarhus Universitetshospital - Department of Cardiology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04443426
- Sponsor's protocol ID
- KETO- CHF 1-10-72-362-18
- Acronym
- KETO-KINETICS1
- Status last verified
- Aug 2022
- First submitted
- 20 May 2019
- Last updated
- 18 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modulation of Circulating Levels of the Ketone Body 3-hydroxybutyrate in Patients With Chronic Heart Failure: Cardiovascular Effects
- ClinicalTrials.gov ID
- NCT04443426
- Acronym / sponsor ID
- KETO-KINETICS1 / KETO- CHF 1-10-72-362-18
- Conditions
- Heart Failure, Ketosis, Ketonemia
- Keywords
- Metabolism
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 8 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Study start
- 25 Apr 2019 (actual)
- Primary completion
- 1 Nov 2022 (estimated)
- Study completion
- 1 Nov 2022 (estimated)
- First posted
- 23 Jun 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.
The ketone body 3-hydroxybutyrate (3-OHB) is a naturally occurring energy substrate, and is associated with increased life span and improved health. We have previously shown that intravenous 3-OHB treatment increases myocardial blood flow > 70% in healthy humans and data from our group show that 3-OHB increases cardiac output by 40 % in patients with heart failure.
In this study the investigators aim to investigate:
- If this effect is reproducible with a commercially available oral ketone supplements
- The safety of commercially available ketone supplements in heart failure patients
Detailed description
Heart Failure (HF) is a major public health issue because the disease affects 1-2% of the Western population and the lifetime risk of HF is 20%. HF is responsible for 1-2% of all healthcare expenditures. Despite major improvements in the management and care of patients with HF, the 1-year mortality in patients with HF is 13 % and >50% of HF-patients is admitted during a 2.5 year period. Furthermore patients with HF have markedly decreased physical capacity and quality of life. Thus, there is a need for new treatment modalities in this group of patients.
Ketone bodies are produced in the liver and are of vital importance in the human body for energy generation in the heart and brain during fasting, exercise and severe illness. Ketosis can be safely obtained using dietary supplements and can increase exercise capacity in athletes. The most important ketone bodies are 3-hydroxybutyrate (3-OHB) and acetoacetate. Recently, it was demonstrated that patients with severe HF have increased myocardial utilization of the ketone body 3-hydroxybutyrate.
We have shown, using positron emission tomography, that ketone body infusion reduces myocardial glucose uptake and increases myocardial blood flow in healthy subjects. Data from another study conducted by our group show a 40% increase in cardiac output during infusion of 3-OHB.
Presently there are no data on the clinical cardiovascular and metabolic effects of long-term oral ketone-supplementation in patients with chronic HF.
In this study the investigators will whether ketosis obtained by oral ketone supplements affects hemodynamics and contractile function.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Single dose oral 3-hydroxybutyrate monoester | Experimental | Dietary Supplement: Ketone MonoesterCross-over study in 8 patients receiving single-dose oral 3-hydroxybutyrate monoester, 3-OHB salt and placebo. |
| Single dose oral 3-hydroxybutyrate Salt | Experimental | Dietary Supplement: Oral 3-hydroxybutyrate salts |
| Single dose oral placebo | Placebo comparator | Dietary Supplement: Carbohydrate Placebomaltodextrin-based, isocaloric to ketone dosis. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Chronic Heart Failure;
- NYHA class II-III
- Left Ventricular Ejection Fraction <40%
Key exclusion criteria (5 listed)
- Diabetes or HbA1c > 48 mmol/mol
- Significant cardiac valve disease,
- Severe stable angina pectoris
- Severe comorbidity as judged by investigator,
- Inability to give informed consent.
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 |
|---|---|---|
| Oral 3-hydroxybutyrate saltsComercially available 3-hydroxybutyrate salts with 36 grams of 3-OHB salts three times daily. | Dietary supplement | Single dose oral 3-hydroxybutyrate Salt |
| Carbohydrate PlaceboComercially available carbohydrate sports drink. The placebo dose is isocaloric to the 3-hydroxy butyrate dose. | Dietary supplement | Single dose oral placebo |
| Ketone MonoesterCommercially available ketone monoester in a dosage isocaloric to 3-OHB salts. | Dietary supplement | Single dose oral 3-hydroxybutyrate monoester |
Primary outcome
Cardiac Output (L/min)
Time frame: 5 hours - Area under the curve
Right Heart Catherization
2 secondary outcomes
Left Ventricle Ejection Fraction (%)
Time frame: 5 Hours - Area under the curve
Left Ventricular filling pressure (mmHg)
Time frame: 5 hours - Area under the curve
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2022.
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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.
Kristian H Christensen, MD principal investigator
Aarhus Universitetshospital - Department of Cardiology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Oral 3-hydroxybutyrate salts and Ketone Monoester in people with Heart Failure and Ketosis, run by University of Aarhus 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 3 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 18 Aug 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Cardiac Output (L/min) (time frame: 5 hours - Area under the curve). 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 18 Aug 2022.