Investigating the Relationship Between Endothelial Cell Activation and Total Pulmonary Resistance in Pulmonary Artery Hypertension (PAH)

Imperial College London0 sites6 target enrollmentNovember 1, 2024

ConditionsPulmonary Artery Hypertension

InterventionsXBD173

DrugsXBD173

Overview

Phase: Not Applicable
Intervention: XBD173
Conditions: Pulmonary Artery Hypertension
Sponsor: Imperial College London
Enrollment: 6
Primary Endpoint: Percentage change in plasma sVCAM1, e-selectin, GDF-15 and NT-proBNP
Status: Not yet recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

To determine whether changes in endothelial cell dysfunction are associated with changes in total pulmonary resistance in patients with pulmonary arterial hypertension

Detailed Description

Patients with PAH will be exposed to XBD173. Markers of endothelial cell dysfunction and activation will be measured in the plasma, and changes in total pulmonary resistance will be meausured with an implantable monitor

Registry

clinicaltrials.gov

Start Date

November 1, 2024

End Date

October 31, 2026

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Imperial College London

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subjects aged between 18-75 years old
•PAH which is: idiopathic; PAH heritable; PAH associated with connective tissue disease; PAH after ≥ 1 year repair of congenital systemic to pulmonary shunt; or PAH associated with anorexignes or other drugs.
•Resting mean pulmonary artery pressure ≥25 mmHg, pulmonary capillary wedge pressure ≤15 mmHg, PVR \>5 wood units, and normal or reduced cardiac output, as measured by a previous right heart catheterisation (RHC).
•Have an insertable FDA/CE cardiac rhythm monitor and pulmonary artery pressure monitor that captures cardiopulmonary haemodynamics and daily activity.
•Six-minute walking distance \>50m at entry
•Stable on an unchanged PAH therapeutic regime comprising at least 2 therapies licensed for PAH (any combination of endothelin receptor antagonist, phosphodiesterase inhibitor or prostacyclin analogue) for at least 1 month prior to screening
•Subjects willing to be genotyped for genes that influence XBD173 activity
•Able to provide written informed consent prior to any study mandated procedures
•Contraception: Fertile females (women of childbearing potential) are eligible to participate after a negative highly sensitive pregnancy test, if they are taking a highly effective method of contraception other than the oral contraceptive pill during treatment and until the end of relevant systemic exposure

Exclusion Criteria

•Unable to provide informed consent and/or are non-fluent speakers of the English language
•Hypersensitivity to XBD173 or to any of the excipients
•Clinically-significant renal disease (confirmed by creatinine clearance \<30 ml/min per 1.73m2)
•Clinically-significant liver disease (confirmed by serum transaminases \>2 times than upper normal limit)
•Anaemia confirmed by haemoglobin concentration \<10 g/dl
•Individuals known to have haemoglobinopathy sickle cell disease, thalassaemia
•Hospital admission related to PAH or change in PAH therapy within 3 months prior to screening
•History of left-sided heart disease and/or clinically significant cardiac disease, including but not limited to any of the following:
•Aortic or mitral valve disease (stenosis or regurgitation) defined as greater than mild aortic insufficiency, mild aortic stenosis, mild mitral stenosis, moderate mitral regurgitation
•Mechanical or bioprosthetic cardiac valve