Ketones for Pulmonary Hypertension - Effects on Hemodynamics

Pulmonary Hypertension Clinical Trial

— KEPAH  

Official title:

Ketone Administration in Patients With Pulmonary Hypertension - Effects on Hemodynamics

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04615754
• Other study ID #: 1-10-72-232-19
• Status: Completed
• Phase: Phase 2
• Start date: August 18, 2020
• Est. completion date: November 29, 2021

Study information

• Verified date: July 2020
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: November 29, 2021
• Est. primary completion date: May 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• Other Significant pulmonary, mitral or aortic valve disease

• Other disease or treatment making subject unsuitable for study participation

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Ketonemia
• Ketosis
• Pulmonary Hypertension

Intervention

Dietary Supplement:
• Hyperketonemia - use of ketone (3-OHB) infusion
The effect of intravenous ketone supplement
• Placebo - use of saline infusion
Saline is infused as an comparator

Locations

Country	Name	City	State
Denmark	Dept. of cardiology, Aarhus University hospital Skejby,	Aarhus	Region Midjylland

Sponsors (2)

Lead Sponsor	Collaborator
University of Aarhus	Danish Heart Foundation

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cardiac output (L/min	Measured by Swan-Ganz monitoring	changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
Secondary	mixed venous saturation (%)	Hemodynamics - Swan Ganz monitoring	changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
Secondary	systemic blood pressure (mmHg)	Hemodynamics - non-invasive blood pressure measurement	changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
Secondary	pulmonary capillary pressure (mmHg)	Hemodynamics - Swan Ganz monitoring	changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
Secondary	Pulmonary pressure (mmHg)	Hemodynamics - Swan Ganz monitoring	changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
Secondary	TAPSE (mm)	Echocardiography	changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
Secondary	RV strain (%)	Echocardiography	changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
Secondary	LV strain (%)	Echocardiography	changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
Secondary	systolic tricuspid plane velocity (cm/sec)	Echocardiography	changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
Secondary	Left ventricular ejection fraction (%)	Echocardiography	changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
Secondary	Changes in Prostaglandines (pmol/L)	Blood samples	changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
Secondary	pH	Blood samples	changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
Secondary	sodium (mM)	Blood samples	changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
Secondary	potassium (mM)	Blood samples	changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
Secondary	lactate (mM)	Blood samples	changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion