The Proteins of the Contact Activation System

NCT ID: NCT02785718

Last Updated: 2016-06-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-30
• Study Completion Date: 2016-09-30

Brief Summary

Cardiovascular diseases are important causes of morbidity and mortality in the industrialized world. Abnormalities in the coagulation system, causing a hypercoagulable state, are a known risk factor for arterial and venous thrombosis. The contact activation system is part of the coagulation system and consists of four proteins: coagulation factor XII (FXII), FXI, prekallikrein and high molecular weight kininogen (HMWK). Clinical studies indicate an important role for the contact activation system on the risk of arterial thrombosis. Furthermore, there is substantial evidence from mouse studies that FXII and FXI participate in the formation and stability of thrombi. In vitro studies show that collagen, present in the vascular wall, is able to activate FXII and hereby stimulate thrombin formation and potentiate the formation of platelet-fibrin thrombi and FXIIa is able to change the structure of fibrin clots by binding to fibrin(ogen) and by generation of additional thrombin. However, the contact system also participates in the process of fibrinolysis, which degrades thrombi.

The investigators would like to investigate the contribution of the contact activation system to the formation of thrombi. The formation of a thrombus within the vascular bed is the main cause for occlusion of an artery or vein, which can lead to an infarct such as a heart attack. Due to the other functions of the contact system it is important to fully understand how the contact system contributes to thrombus formation, before it can be used as a target in the treatment of arterial thrombosis. The aim of this study is to determine the contribution of the proteins of the contact system, mainly FXII and FXI, in the platelet mediated formation and degradation of thrombi. This will be studied in flow models (perfusion-flow model and Chandler loop), in a static model (ROTEM®) and using thrombin generation assay.

Conditions

Factor XI Deficiency; Factor XII Deficiency

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Blinding Strategy: NONE

Study Groups

Patients with FXI or FXII deficiency

12 patients with FXI deficiency and 6 patients with FXII deficiency

Group Type: EXPERIMENTAL

Global Haemostasis assays

Intervention Type: OTHER

Interventions

Global Haemostasis assays

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Deficiency in coagulation factor XII and factor XI (factor level<5%)
• Subjects of both gender
• Age ≥18 and ≤ 65
• Written informed consent from the subject
• Subject with a social security plan or beneficiary of such a plan.

Exclusion Criteria

• Age below 18
• Age above 65
• Other known abnormalities of the coagulation system
• Thrombocytopenia
• Known platelet disorders
• Personal history of severe liver diseases
• Symptoms of active disease (e.g. cancer)
• The use of antiplatelet drugs
• The use of drugs that interfere with coagulation
• Ongoing diagnosed pregnancy upper 3 months
• Adult patients protected by law
• Concomitant participation to a biomedical research

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Unité d'Hémostase Clinique Hôpital Louis Pradel

Bron, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Yesim DARGAUD, MD PHD

Role: CONTACT

ydargaud@univ-lyon1.fr

(0)4 72 11 88 25 ext. +33

Facility Contacts

Yesim Dargaud, MD, PhD

Role: primary

ydargaud@univ-lyon1.fr

(0)4 72 11 88 25 ext. +33

Other Identifiers

2012.785

Identifier Type: -

Identifier Source: org_study_id