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

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ClinicalTrials.gov Identifier: NCT03287999
Recruitment Status : Not yet recruiting
First Posted : September 19, 2017
Last Update Posted : September 19, 2017
Sponsor:
Information provided by (Responsible Party):
Pratima Chowdary, Royal Free Hospital NHS Foundation Trust

Brief Summary:
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.

Condition or disease Intervention/treatment
Haemophilia Diagnostic Test: Thrombophilia screen Diagnostic Test: Initiation pathway analysis

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Study Type : Observational
Estimated Enrollment : 250 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Inter Individual Variability in Initiation Pathway Activation and Regulation and Phenotypic Heterogeneity in Patients With Haemophilia A and B
Estimated Study Start Date : October 2, 2017
Estimated Primary Completion Date : October 2, 2018
Estimated Study Completion Date : October 2, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemophilia

Group/Cohort Intervention/treatment
Haemophilia patients
Persons with haemophilia A or B - 240 to be recruited
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)

Healthy volunteers
Healthy volunteers - 10 to be recruited
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)




Primary Outcome Measures :
  1. Initiation pathway correlation with clinical phenotype [ Time Frame: Within 18 months of consent ]
    Correlate lab assays that characterise initiation pathway with clinical phenotype.


Secondary Outcome Measures :
  1. 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 ]
  2. Evaluation the sensitivity and specificity of global assays for disease severity and clinical phenotype. [ Time Frame: Within 18 months of consent ]
  3. Correlation analysis between activation threshold of initiation pathway to thrombin generation and clinical phenotype [ Time Frame: Within 18 months of consent ]

Biospecimen Retention:   Samples With DNA
Blood plasma


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
The study population will include patients severe or moderate haemophilia A or B who are currently attending study sites for routine follow up visits. In addition, 10 healthy volunteers will also be recruited to act as controls
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03287999


Contacts
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Contact: Thomas Roberts 02078302068 thomas.roberts1@nhs.net

Locations
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United Kingdom
Royal Free Hospital Not yet recruiting
London, United Kingdom
Contact: Thomas Roberts         
Principal Investigator: Pratima Chowdary         
Sponsors and Collaborators
Royal Free Hospital NHS Foundation Trust
Investigators
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Principal Investigator: Pratima Chowdary Royal Free Hospitals NHS Foundation Trust

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Responsible Party: Pratima Chowdary, Dr Pratima Chowdary, Royal Free Hospital NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT03287999     History of Changes
Other Study ID Numbers: 11296
First Posted: September 19, 2017    Key Record Dates
Last Update Posted: September 19, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants