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Pulmonary HypertensionPhase 2KEPAHNCT04615754

Ketones for Pulmonary Hypertension - Effects on Hemodynamics

A Phase 2 study testing Hyperketonemia - use of ketone (3-OHB) infusion in people with Pulmonary Hypertension and Ketonemia, run by University of Aarhus at 1 site in Denmark.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

In the present study, patients with idiopathic pulmonary hypertension (IPAH) and chronic thromboembolic pulmonary hypertenion will be investigated in a randomized cross-over design with ketone infusions and placebo. Invasive and non-invasive hemodynamics will be evaluated Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Pulmonary Hypertension, Ketonemia
What is being tested?
Hyperketonemia - use of ketone (3-OHB) infusion
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
20 participants
Where
1 siteDenmark
Study dates
18 Aug 2020to 29 Nov 2021
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

  • Persistent pulmonary hypertension (defined as PVR > 3 WU, pulmonary capillary wedge pressure (PCWP) < 15 mmHG, mean pulmonary arterial pressure (mPAP) ≥25 mmHg) on the most resent right heart catheterization.
  • Preserved left ventricular ejection fraction (<50%) on most recent echocardiography
  • Able to give informed consent

Who cannot join

  • Other Significant pulmonary, mitral or aortic valve disease
  • Other disease or treatment making subject unsuitable for study participation

Trial locations and contacts

1 site in 1 country.

Denmark1 site

  • Dept. of cardiology, Aarhus University hospital Skejby,

    Aarhus, Region Midjylland, 8200

Other trials in Denmark

About this study

Official title: Ketone Administration in Patients With Pulmonary Hypertension - Effects on Hemodynamics

In the present study, patients with idiopathic pulmonary hypertension (IPAH) and chronic thromboembolic pulmonary hypertenion will be investigated in a randomized cross-over design with ketone infusions and placebo. Invasive and non-invasive hemodynamics will be evaluated

Read the detailed description

Pulmonary hypertension (PH) is a debilitating disease that affects both the pulmonary vasculature and the heart. It is associated with increased mortality and hospitalization and impairs daily life for the affected patients. Despite substantial advances in treatment within the past decade the prognosis remains poor with an 1-year mortality of more than 10%.1 The pathophysiology of PH is multifactorial and can be caused by left sided cardiac disease, pulmonary pathophysiological changes in the pulmonary vessels, respiratory diseases and pulmonary embolism.The treatment is targeted at the underlying cause. Hence, left sided heart disease is treated with anticongestive medications4 and respiratory disease by pulmonary medications. However, pulmonary vascular diseases such as chronic thromboembolic pulmonary hypertension (CTEPH) and idiopathic pulmonary arterial hypertension (IPAH) are treated with pulmonary endarterectomy and vasodilators targeting the pulmonary vasculature, respectively. However, not all patients have an optimal pulmonary hemodynamic response on treatment. If patients are left with persistent pulmonary hypertension the disease may progress further and cause right heart failure which worsens the prognosis.

Data from a recent study conducted at the investigator's institution demonstrated 40% increase in cardiac output during infusion of the ketone body 3-hydroxybutyrate (3-OHB). Intriguingly, this was associated with an increase in RV function and a decrease in the pulmonary vascular resistance of approximately 20%.

In the present study, 10 patients with IPAH and 10 patients with CETPH will be subjected to placebo and 3-OHB infusion in a randomized cross-over design. Each of the infusions will be given for 2.5 hours and cross-over will be carried out on the same day. Echocardiography and right sided heart catheterization will be applied and blood will be sampled.

Being tested
Hyperketonemia - use of ketone (3-OHB) infusion, Placebo - use of saline infusion
Keywords
Right sided heart catheterization, Echocardiography, Hemodynamics
Medical subject headings
Hypertension, Pulmonary, Ketosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Hyperketonemia - use of ketone (3-OHB) infusionDietary supplement

    The effect of intravenous ketone supplement

  • Placebo - use of saline infusionDietary supplement

    Saline is infused as an comparator

Study groups in NCT04615754
Study groupRoleWhat they receive
3-OHB vs SalineExperimental3-OHB will be infused for 2.5 hours in IPAH (n=5) and CETPH (n=5) patients- 6 in each group is recruited for taking drop-out into account
Receives: Dietary Supplement: Hyperketonemia - use of ketone (3-OHB) infusion; Dietary Supplement: Placebo - use of saline infusion
Saline vs 3-OHBExperimentalSaline will be infused for 2.5 hours in IPAH (n=5) and CETPH (n=5) patients- 6 in each group is recruited for taking drop-out into account
Receives: Dietary Supplement: Hyperketonemia - use of ketone (3-OHB) infusion; Dietary Supplement: Placebo - use of saline infusion

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Cardiac output (L/min

    Measured by Swan-Ganz monitoring

    Measured: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion

Secondary outcomes (14)

  1. mixed venous saturation (%)

    Hemodynamics - Swan Ganz monitoring

    Measured: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion

  2. systemic blood pressure (mmHg)

    Hemodynamics - non-invasive blood pressure measurement

    Measured: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion

  3. pulmonary capillary pressure (mmHg)

    Hemodynamics - Swan Ganz monitoring

    Measured: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion

  4. Pulmonary pressure (mmHg)

    Hemodynamics - Swan Ganz monitoring

    Measured: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion

  5. TAPSE (mm)

    Echocardiography

    Measured: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion

  6. RV strain (%)

    Echocardiography

    Measured: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion

  7. LV strain (%)

    Echocardiography

    Measured: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion

  8. systolic tricuspid plane velocity (cm/sec)

    Echocardiography

    Measured: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion

  9. Left ventricular ejection fraction (%)

    Echocardiography

    Measured: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion

  10. Changes in Prostaglandines (pmol/L)

    Blood samples

    Measured: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion

  11. pH

    Blood samples

    Measured: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion

  12. sodium (mM)

    Blood samples

    Measured: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion

  13. potassium (mM)

    Blood samples

    Measured: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion

  14. lactate (mM)

    Blood samples

    Measured: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Nov 2020
  2. Study start18 Aug 2020
  3. Primary completion1 May 2021
  4. Study completion29 Nov 2021

Resources

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
Model description
Randomized cross-over I.e. Ketone infusion is compared to saline infusion in a randomised cross-ove design. (Ketones are considered dietary supplement as glucose or lipids)
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04615754
Sponsor's protocol ID
1-10-72-232-19
Acronym
KEPAH
Status last verified
Jul 2020
First submitted
10 Aug 2020
Last updated
2 Dec 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Nielsen R, Christensen KH, Gopalasingam N, Berg-Hansen K, Seefeldt J, Homilius C, Boedtkjer E, Andersen MJ, Wiggers H, Moller N, Botker HE, Mellemkjaer S. Hemodynamic Effects of Ketone Bodies in Patients With Pulmonary Hypertension. J Am Heart Assoc. 2023 May 16;12(10):e028232. doi: 10.1161/JAHA.122.028232. Epub 2023 May 15.

    PubMed 37183871

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Hyperketonemia - use of ketone (3-OHB) infusion in people with Pulmonary Hypertension and Ketonemia, 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 2 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 2 Dec 2021. 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. 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?

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?

Cardiac output (L/min (time frame: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04615754, which also lists 1 linked publication.

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 2 Dec 2021.

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