Ketones for Pulmonary Hypertension - Effects on Hemodynamics (KEPAH)

University of Aarhus

Status and phase: Completed; Phase 2

Conditions: Ketonemia; Pulmonary Hypertension

Treatments: Dietary Supplement: Placebo - use of saline infusion; Dietary Supplement: Hyperketonemia - use of ketone (3-OHB) infusion

Study type: Interventional

Funder types: Other

Identifiers

NCT04615754

1-10-72-232-19

Details and patient eligibility

About

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

Full 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.

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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20 participants in 2 patient groups

3-OHB vs Saline

Experimental group

Description:

3-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

Treatment:

Dietary Supplement: Hyperketonemia - use of ketone (3-OHB) infusion

Dietary Supplement: Placebo - use of saline infusion

Saline vs 3-OHB

Experimental group

Description:

Saline 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

Treatment:

Dietary Supplement: Hyperketonemia - use of ketone (3-OHB) infusion

Dietary Supplement: Placebo - use of saline infusion