Clinical trial NCT04615754: Ketones for Pulmonary Hypertension - Effects on Hemodynamics
Official title: Ketone Administration in Patients With Pulmonary Hypertension - Effects on Hemodynamics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Hypertension
Ketonemia
Keywords: Right sided heart catheterization
Echocardiography
Hemodynamics
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Danish Heart Foundation
First posted: 2020-11-04
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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)
Primary purpose: TREATMENT

Brief 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Cardiac output (L/min
timeFrame: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
Secondary outcomes:
measure: mixed venous saturation (%)
timeFrame: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
measure: systemic blood pressure (mmHg)
timeFrame: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
measure: pulmonary capillary pressure (mmHg)
timeFrame: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
measure: Pulmonary pressure (mmHg)
timeFrame: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
measure: TAPSE (mm)
timeFrame: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
measure: RV strain (%)
timeFrame: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
measure: LV strain (%)
timeFrame: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
measure: systolic tricuspid plane velocity (cm/sec)
timeFrame: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
measure: Left ventricular ejection fraction (%)
timeFrame: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
measure: Changes in Prostaglandines (pmol/L)
timeFrame: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
measure: pH
timeFrame: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
measure: sodium (mM)
timeFrame: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
measure: potassium (mM)
timeFrame: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
measure: lactate (mM)
timeFrame: changes during the infusion for 2.5 hours compared to 2.5 hours of Saline infusion
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Dept. of cardiology, Aarhus University hospital Skejby,
state: Region Midjylland
Study officials:
affiliation: Dept. of Cardiology, Aarhus University Hospital
name: Roni R Nielsen, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: