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Endothelial Cell Activation and Total Pulmonary Resistance in PAH

Sponsor
Imperial College London (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT06035861
Collaborator
(none)
6
Enrollment
1
Arm
36
Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
N/A

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

Study Design

Study Type:
Interventional
Anticipated Enrollment :
6 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
Investigating the Relationship Between Endothelial Cell Activation and Total Pulmonary Resistance in Pulmonary Artery Hypertension (PAH)
Anticipated Study Start Date :
Nov 1, 2023
Anticipated Primary Completion Date :
Oct 31, 2026
Anticipated Study Completion Date :
Oct 31, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: XBD173

8 weeks exposure to XBD173

Drug: XBD173
Participants will be treated with XBD173 90mg, once or twice daily, for 8 weeks
Other Names:
  • AC5216

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage change in plasma sVCAM1, e-selectin, GDF-15 and NT-proBNP [8 weeks]

      Percentage change in plasma markers

    2. Percentage change in total pulmonary resistance [8 weeks]

      Percentage change in total pulmonary resistance

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Subjects aged between 18-75 years old

    2. 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.

    3. 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).

    4. Have an insertable FDA/CE cardiac rhythm monitor and pulmonary artery pressure monitor that captures cardiopulmonary haemodynamics and daily activity.

    5. Six-minute walking distance >50m at entry

    6. 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

    7. Subjects willing to be genotyped for genes that influence XBD173 activity

    8. Able to provide written informed consent prior to any study mandated procedures

    9. 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:

    1. Unable to provide informed consent and/or are non-fluent speakers of the English language

    2. Hypersensitivity to XBD173 or to any of the excipients

    3. Clinically-significant renal disease (confirmed by creatinine clearance <30 ml/min per 1.73m2)

    4. Clinically-significant liver disease (confirmed by serum transaminases >2 times than upper normal limit)

    5. Anaemia confirmed by haemoglobin concentration <10 g/dl

    6. Individuals known to have haemoglobinopathy sickle cell disease, thalassaemia

    7. Hospital admission related to PAH or change in PAH therapy within 3 months prior to screening

    8. History of left-sided heart disease and/or clinically significant cardiac disease, including but not limited to any of the following:

    9. Aortic or mitral valve disease (stenosis or regurgitation) defined as greater than mild aortic insufficiency, mild aortic stenosis, mild mitral stenosis, moderate mitral regurgitation

    10. Mechanical or bioprosthetic cardiac valve

    11. Pericardial constriction, effusion with tamponade physiology, or abnormal left atrial size.

    12. Restrictive or congestive cardiomyopathy

    13. Left ventricular ejection fraction ≤50% (measured in echocardiogram at screening)

    14. Symptomatic coronary disease

    15. Significant (2+ for regurgitation) valvular disease other than tricuspid or pulmonary regurgitation

    16. Acutely decompensated left heart failure within 1 month of screening

    17. History of untreated obstructive sleep apnoea

    18. Evidence of significant lung disease on high-resolution CT (if available) or recent (performed within 12 months) lung function, where FEV1 < 50% predicted and FVC < 70% predicted, and DLCO (or TLCO) < 50% predicted if any CT abnormalities; judged by the Site Physician

    19. Patients with a history of uncontrolled systemic hypertension

    20. Acute infection (including eye, dental, and skin infections)

    21. Chronic inflammatory disease including HIV, and Hepatitis B

    22. Women of childbearing potential who are pregnant or breastfeeding (if applicable)

    23. Patients who have received an Investigational Medicinal Product (IMP) within 5 half-lives of the last dose of the IMP or 1 month (which ever is greater) before the baseline visit

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Imperial College London

    Investigators

    None specified.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Imperial College London
    ClinicalTrials.gov Identifier:
    NCT06035861
    Other Study ID Numbers:
    • 22HH7807
    First Posted:
    Sep 13, 2023
    Last Update Posted:
    Sep 13, 2023
    Last Verified:
    Sep 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Pulmonary Arterial Hypertension
    Hypertension

    Study Results

    No Results Posted as of Sep 13, 2023