Inter Individual Variability in Initiation Pathway Activation and Regulation and Phenotypic Heterogeneity in Patients With Haemophilia A and B

Overview

Severe haemophilia A and B (SHA, SHB) are X – linked inherited bleeding disorders, characterised by factor VIII and IX levels of <1 IU/dL respectively. The mainstay of treatment in SHA and SHB is replacement therapy with intravenous infusions of factor VIII and IX. However, there is significant variability in the bleeding phenotype within severe haemophiliacs with some presenting with minimal bleeding episodes even on less intensive treatment regimens. A significant contributor to inter-individual variability in the bleeding phenotype is the coagulation phenotype, but there are no established assays in routine clinical practice that can be used to quantify this. This study aims to study novel assays and characterise the observed phenotypic heterogeneity.

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: October 2, 2019

Interventions

  • Diagnostic Test: Thrombophilia screen
    • Thrombophilia screen (including antithrombin activity (AT:Ac), protein S antigen (PS:free), protein C activity (PC:Ac) , genetic analysis for FV Leiden and Prothrombin 3′UTR mutations and screening for lupus anticoagulant.
  • Diagnostic Test: Initiation pathway analysis
    • Evaluation of inter-individual variability in regulation of TF.VIIa.Xa.TFPI complex (tissue factor, activated Factor VII, activated factor X, tissue factor pathway inhibitor)

Arms, Groups and Cohorts

  • Haemophilia patients
    • Persons with haemophilia A or B – 240 to be recruited
  • Healthy volunteers
    • Healthy volunteers – 10 to be recruited

Clinical Trial Outcome Measures

Primary Measures

  • Initiation pathway correlation with clinical phenotype
    • Time Frame: Within 18 months of consent
    • Correlate lab assays that characterise initiation pathway with clinical phenotype.

Secondary Measures

  • Correlation analysis between FVIII:C/FIX:C levels and whole blood clotting time, thrombin generation in platelet poor plasma.
    • Time Frame: Within 18 months of consent
  • Evaluation the sensitivity and specificity of global assays for disease severity and clinical phenotype.
    • Time Frame: Within 18 months of consent
  • Correlation analysis between activation threshold of initiation pathway to thrombin generation and clinical phenotype
    • Time Frame: Within 18 months of consent

Participating in This Clinical Trial

Patients Inclusion Criteria:

1. Patients with haemophilia A or B (baseline FVIII/FIX level <30%) 2. Age ≥ 18 years 3. Written informed consent in accordance with local and institutional guidelines. Exclusion Criteria:

1. Patients currently enrolled into a clinical trial of investigational medicinal product for haemophilia. Healthy Volunteers Inclusion Criteria:

1. Currently not receiving any antiplatelet or anticoagulant therapy or other drugs that can affect the coagulation system. 2. Age ≥ 18 years 3. Written informed consent in accordance with local and institutional guidelines.

Gender Eligibility: Male

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Royal Free Hospital NHS Foundation Trust
  • Provider of Information About this Clinical Study
    • Principal Investigator: Pratima Chowdary, Dr Pratima Chowdary – Royal Free Hospital NHS Foundation Trust
  • Overall Official(s)
    • Pratima Chowdary, Principal Investigator, Royal Free Hospitals NHS Foundation Trust
  • Overall Contact(s)
    • Thomas Roberts, 02078302068, thomas.roberts1@nhs.net

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.