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Evaluation of the Hemostatic Potential in Sickle Cell Disease Patients

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ClinicalTrials.gov Identifier: NCT02565082
Recruitment Status : Completed
First Posted : October 1, 2015
Last Update Posted : July 26, 2016
Sponsor:
Information provided by (Responsible Party):
Dr Anne Demulder, Brugmann University Hospital

Tracking Information
First Submitted Date  ICMJE September 18, 2015
First Posted Date  ICMJE October 1, 2015
Last Update Posted Date July 26, 2016
Study Start Date  ICMJE September 2015
Actual Primary Completion Date July 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 15, 2016)
  • Coagulation markers [ Time Frame: sickle cell patients - stable condition - at upcoming hospital routine follow-up, within maximum two years time ]
    The following coagulation markers will be assessed in the blood samples: thrombin and thrombomodulin, protein C, protein S, antithrombin, D-dimer, factor VIII, TFPI (physiological inhibitor of the extrinsic pathway of coagulation). This will be measured only once for each patient, for this health status.
  • Coagulation markers [ Time Frame: sickle cell patients - if exsanguinotransfusion needed - immediately prior exsanguinotransfusion, within maximum two years time ]
    The following coagulation markers will be assessed in the blood samples:thrombin and thrombomodulin, protein C, protein S, antithrombin, D-dimer, factor VIII, TFPI (physiological inhibitor of the extrinsic pathway of coagulation). This will be measured only once for each patient, for this health status.
  • Coagulation markers [ Time Frame: sickle cell patients - if exsanguinotransfusion needed - immediately after exsanguinotransfusion, within maximum two years time ]
    The following coagulation markers will be assessed in the blood samples:thrombin and thrombomodulin, protein C, protein S, antithrombin, D-dimer, factor VIII, TFPI (physiological inhibitor of the extrinsic pathway of coagulation). This will be measured only once for each patient, for this health status.
  • Coagulation markers [ Time Frame: sickle cell patients - if vaso-occlusive crisis - during the vaso-occlusive crisis, within maximum two years time ]
    The following coagulation markers will be assessed in the blood samples:thrombin and thrombomodulin, protein C, protein S, antithrombin, D-dimer, factor VIII, TFPI (physiological inhibitor of the extrinsic pathway of coagulation). This will be measured only once for each patient, for this health status.
  • Coagulation markers [ Time Frame: healthy volunteers: after informed consent signature, within maximum two years time ]
    The following markers will be assessed in the blood samples:thrombin and thrombomodulin, protein C, protein S, antithrombin, D-dimer, factor VIII, TFPI (physiological inhibitor of the extrinsic pathway of coagulation). This will be measured only once for each volunteer.
  • Hemolysis markers [ Time Frame: sickle cell patients - stable condition - at upcoming hospital routine follow-up, within maximum two years time ]
    Will be measured in the blood samples by the following markers:plasmatic hemoglobin level and the lactate dehydrogenase level.This will be measured only once for each patient, for this health status.
  • Hemolysis markers [ Time Frame: sickle cell patients - if exsanguinotransfusion needed - immediately prior exsanguinotransfusion, within maximum two years time ]
    Will be measured in the blood samples by the following markers:plasmatic hemoglobin level and the lactate dehydrogenase level.This will be measured only once for each patient, for this health status.
  • Hemolysis markers [ Time Frame: sickle cell patients - if exsanguinotransfusion needed - immediately after exsanguinotransfusion, within maximum two years time ]
    Will be measured in the blood samples by the following markers:plasmatic hemoglobin level and the lactate dehydrogenase level.This will be measured only once for each patient, for this health status.
  • Hemolysis markers [ Time Frame: sickle cell patients - if vaso-occlusive crisis - during the vaso-occlusive crisis, within maximum two years time ]
    Will be measured in the blood samples by the following markers:plasmatic hemoglobin level and the lactate dehydrogenase level.This will be measured only once for each patient, for this health status.
  • Hemolysis markers [ Time Frame: healthy volunteers: after informed consent signature, within maximum two years time ]
    Will be measured in the blood samples by the following markers:plasmatic hemoglobin level and the lactate dehydrogenase level.This will be measured only once for each volunteer.
  • Microparticles level [ Time Frame: sickle cell patients - stable condition - at upcoming hospital routine follow-up, within maximum two years time ]
    Will be measured in the blood samples both by a capture method (Zymuphen) and FACS.This will be measured only once for each patient, for this health status.
  • Microparticles level [ Time Frame: sickle cell patients -if exsanguinotransfusion - immediately prior exsanguinotransfusion, within maximum two years time ]
    Will be measured in the blood samples both by a capture method (Zymuphen) and FACS. This will be measured only once for each patient, for this health status.
  • Microparticles level [ Time Frame: sickle cell patients - if exsanguinotransfusion needed - immediately after exsanguinotransfusion, within maximum two years time ]
    Will be measured in the blood samples both by a capture method (Zymuphen) and FACS.This will be measured only once for each patient, for this health status.
  • Microparticles level [ Time Frame: sickle cell patients - if vaso-occlusive crisis - during the vaso-occlusive crisis, within maximum two years time ]
    Will be measured both by a capture method (Zymuphen) and FACS.This will be measured only once for each patient, for this health status.
  • Microparticles level [ Time Frame: healthy volunteers: after informed consent signature, within maximum two years time ]
    Will be measured in the blood samples both by a capture method (Zymuphen) and FACS. This will be measured only once for each patient, for this health status.
  • Inflammatory markers [ Time Frame: sickle cell patients - stable condition - at upcoming hospital routine follow-up, within maximum two years time ]
    The following markers will be assessed in the blood samples: inflammatory cytokines, TNF, usCRP and interleukines. This will be measured only once for each patient, for this health status.
  • Inflammatory markers [ Time Frame: sickle cell patients - if exsanguinotransfusion needed - immediately prior exsanguinotransfusion, within maximum two years time ]
    The following markers will be assessed in the blood samples: inflammatory cytokines, TNF, usCRP and interleukines. This will be measured only once for each patient, for this health status.
  • Inflammatory markers [ Time Frame: sickle cell patients - if exsanguinotransfusion needed - immediately after exsanguinotransfusion, within maximum two years time ]
    The following markers will be assessed in the blood samples: inflammatory cytokines, TNF, usCRP and interleukines. This will be measured only once for each patient, for this health status.
  • Inflammatory markers [ Time Frame: sickle cell patients - if vaso-occlusive crisis - during the vaso-occlusive crisis, within maximum two years time ]
    The following markers will be assessed in the blood samples: inflammatory cytokines, TNF, usCRP and interleukines. This will be measured only once for each patient, for this health status.
  • Inflammatory markers [ Time Frame: healthy volunteers - after informed consent signature, within maximum two years time ]
    The following markers will be assessed in the blood samples: inflammatory cytokines, TNF, usCRP and interleukines. This will be measured only once for each volunteer.
  • Vascular markers [ Time Frame: sickle cell patients - stable condition - at upcoming hospital routine follow-up, within maximum two years time ]
    The following markers will be assessed in the blood samples: soluble thrombomodulin, von Willebrand factor, vascular endothelial growth factor, protein C endothelial factor. This will be measured only once for each patient, for this health status
  • Vascular markers [ Time Frame: sickle cell patients - if exsanguinotransfusion needed - immediately prior exsanguinotransfusion, within maximum two years time ]
    The following markers will be assessed in the blood samples: soluble thrombomodulin, von Willebrand factor, vascular endothelial growth factor, protein C endothelial factor. This will be measured only once for each patient, for this health status
  • Vascular markers [ Time Frame: sickle cell patients - if exsanguinotransfusion needed - immediately after exsanguinotransfusion, within maximum two years time ]
    The following markers will be assessed in the blood samples: soluble thrombomodulin, von Willebrand factor, vascular endothelial growth factor, protein C endothelial factor. This will be measured only once for each patient, for this health status
  • Vascular markers [ Time Frame: healthy volunteers - after informed consent signature, within maximum two years time ]
    The following markers will be assessed in the blood samples: soluble thrombomodulin, von Willebrand factor, vascular endothelial growth factor, protein C endothelial factor. This will be measured only once for each volunteer.
Original Primary Outcome Measures  ICMJE
 (submitted: September 30, 2015)
  • Coagulation markers [ Time Frame: sickle cell patients - stable condition - at upcoming hospital routine follow-up, within maximum two years time ]
    The following coagulation markers will be assessed in the blood samples: thrombin and thrombomodulin, protein C, protein S, antithrombin, D-dimer, factor VIII, TFPI (physiological inhibitor of the extrinsic pathway of coagulation). This will be measured only once for each patient, for this health status.
  • Coagulation markers [ Time Frame: sicke cell patients - if exsanguinotransfusion needed - immediately prior exsanguinotransfusion, within maximum two years time ]
    The following coagulation markers will be assessed in the blood samples:thrombin and thrombomodulin, protein C, protein S, antithrombin, D-dimer, factor VIII, TFPI (physiological inhibitor of the extrinsic pathway of coagulation). This will be measured only once for each patient, for this health status.
  • Coagulation markers [ Time Frame: sicke cell patients - if exsanguinotransfusion needed - immediately after exsanguinotransfusion, within maximum two years time ]
    The following coagulation markers will be assessed in the blood samples:thrombin and thrombomodulin, protein C, protein S, antithrombin, D-dimer, factor VIII, TFPI (physiological inhibitor of the extrinsic pathway of coagulation). This will be measured only once for each patient, for this health status.
  • Coagulation markers [ Time Frame: sickle cell patients - if vaso-occlusive crisis - during the vaso-occlusive crisis, within maximum two years time ]
    The following coagulation markers will be assessed in the blood samples:thrombin and thrombomodulin, protein C, protein S, antithrombin, D-dimer, factor VIII, TFPI (physiological inhibitor of the extrinsic pathway of coagulation). This will be measured only once for each patient, for this health status.
  • Coagulation markers [ Time Frame: healthy volunteers: after informed consent signature, within maximum two years time ]
    The following markers will be assessed in the blood samples:thrombin and thrombomodulin, protein C, protein S, antithrombin, D-dimer, factor VIII, TFPI (physiological inhibitor of the extrinsic pathway of coagulation). This will be measured only once for each volunteer.
  • Hemolysis markers [ Time Frame: sickle cell patients - stable condition - at upcoming hospital routine follow-up, within maximum two years time ]
    Will be measured in the blood samples by the following markers:plasmatic hemoglobin level and the lactate dehydrogenase level.This will be measured only once for each patient, for this health status.
  • Hemolysis markers [ Time Frame: sicke cell patients - if exsanguinotransfusion needed - immediately prior exsanguinotransfusion, within maximum two years time ]
    Will be measured in the blood samples by the following markers:plasmatic hemoglobin level and the lactate dehydrogenase level.This will be measured only once for each patient, for this health status.
  • Hemolysis markers [ Time Frame: sicke cell patients - if exsanguinotransfusion needed - immediately after exsanguinotransfusion, within maximum two years time ]
    Will be measured in the blood samples by the following markers:plasmatic hemoglobin level and the lactate dehydrogenase level.This will be measured only once for each patient, for this health status.
  • Hemolysis markers [ Time Frame: sickle cell patients - if vaso-occlusive crisis - during the vaso-occlusive crisis, within maximum two years time ]
    Will be measured in the blood samples by the following markers:plasmatic hemoglobin level and the lactate dehydrogenase level.This will be measured only once for each patient, for this health status.
  • Hemolysis markers [ Time Frame: healthy volunteers: after informed consent signature, within maximum two years time ]
    Will be measured in the blood samples by the following markers:plasmatic hemoglobin level and the lactate dehydrogenase level.This will be measured only once for each volunteer.
  • Microparticles level [ Time Frame: sickle cell patients - stable condition - at upcoming hospital routine follow-up, within maximum two years time ]
    Will be measured in the blood samples both by a capture method (Zymuphen) and FACS.This will be measured only once for each patient, for this health status.
  • Microparticles level [ Time Frame: sicke cell patients -if exsanguinotransfusion - immediately prior exsanguinotransfusion, within maximum two years time ]
    Will be measured in the blood samples both by a capture method (Zymuphen) and FACS. This will be measured only once for each patient, for this health status.
  • Microparticles level [ Time Frame: sicke cell patients - if exsanguinotransfusion needed - immediately after exsanguinotransfusion, within maximum two years time ]
    Will be measured in the blood samples both by a capture method (Zymuphen) and FACS.This will be measured only once for each patient, for this health status.
  • Microparticles level [ Time Frame: sickle cell patients - if vaso-occlusive crisis - during the vaso-occlusive crisis, within maximum two years time ]
    Will be measured both by a capture method (Zymuphen) and FACS.This will be measured only once for each patient, for this health status.
  • Microparticles level [ Time Frame: healthy volunteers: after informed consent signature, within maximum two years time ]
    Will be measured in the blood samples both by a capture method (Zymuphen) and FACS. This will be measured only once for each patient, for this health status.
  • Inflammatory markers [ Time Frame: sickle cell patients - stable condition - at upcoming hospital routine follow-up, within maximum two years time ]
    The following markers will be assessed in the blood samples: inflammatory cytokines, TNF, usCRP and interleukines. This will be measured only once for each patient, for this health status.
  • Inflammatory markers [ Time Frame: sicke cell patients - if exsanguinotransfusion needed - immediately prior exsanguinotransfusion, within maximum two years time ]
    The following markers will be assessed in the blood samples: inflammatory cytokines, TNF, usCRP and interleukines. This will be measured only once for each patient, for this health status.
  • Inflammatory markers [ Time Frame: sicke cell patients - if exsanguinotransfusion needed - immediately after exsanguinotransfusion, within maximum two years time ]
    The following markers will be assessed in the blood samples: inflammatory cytokines, TNF, usCRP and interleukines. This will be measured only once for each patient, for this health status.
  • Inflammatory markers [ Time Frame: sickle cell patients - if vaso-occlusive crisis - during the vaso-occlusive crisis, within maximum two years time ]
    The following markers will be assessed in the blood samples: inflammatory cytokines, TNF, usCRP and interleukines. This will be measured only once for each patient, for this health status.
  • Inflammatory markers [ Time Frame: healthy volunteers - after informed consent signature, within maximum two years time ]
    The following markers will be assessed in the blood samples: inflammatory cytokines, TNF, usCRP and interleukines. This will be measured only once for each volunteer.
  • Vascular markers [ Time Frame: sickle cell patients - stable condition - at upcoming hospital routine follow-up, within maximum two years time ]
    The following markers will be assessed in the blood samples: soluble thrombomodulin, von Willebrand factor, vascular endothelial growth factor, protein C endothelial factor. This will be measured only once for each patient, for this health status
  • Vascular markers [ Time Frame: sicke cell patients - if exsanguinotransfusion needed - immediately prior exsanguinotransfusion, within maximum two years time ]
    The following markers will be assessed in the blood samples: soluble thrombomodulin, von Willebrand factor, vascular endothelial growth factor, protein C endothelial factor. This will be measured only once for each patient, for this health status
  • Vascular markers [ Time Frame: sicke cell patients - if exsanguinotransfusion needed - immediately after exsanguinotransfusion, within maximum two years time ]
    The following markers will be assessed in the blood samples: soluble thrombomodulin, von Willebrand factor, vascular endothelial growth factor, protein C endothelial factor. This will be measured only once for each patient, for this health status
  • Vascular markers [ Time Frame: healthy volunteers - after informed consent signature, within maximum two years time ]
    The following markers will be assessed in the blood samples: soluble thrombomodulin, von Willebrand factor, vascular endothelial growth factor, protein C endothelial factor. This will be measured only once for each volunteer.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of the Hemostatic Potential in Sickle Cell Disease Patients
Official Title  ICMJE Evaluation of the Hemostatic Potential in Sickle Cell Disease Patients
Brief Summary

Sickle cell disease is a genetic disorder caused by a point mutation on the amino acid sequence of the β chain of hemoglobin.

The most expressive and most frequent complication of the disease is vaso-occlusive crisis, dominated by a painful syndrome. In addition to vaso-occlusive crises, many more chronic biological disturbances are observed in sickle cell patients.Sickle cell disease is considered nowadays as a hypercoagulable state.

However, the approach used so far to the measure of clotting in sickle cell disease was segmented in the sense that the various components of the hemostatic balance were studied separately.The thrombin generation test is a functional test which explores the coagulation globally, integrating both pro players that anticoagulants actors in the system. The investigators already used this test to demonstrate that the hemostatic potential was high in a cohort of affected children compared to control children of the same age.

This test will be used to characterize the hemostatic potential of adult sickle cell patients followed at the CHU Brugmann Hospital.

Detailed Description

Sickle cell disease is a genetic disorder caused by a point mutation on the amino acid sequence of the β chain of hemoglobin. This is the most common genetic disease in the world. The majority of patients are in Sub-Saharan Africa; however, the increase in migratory movements of populations helps to move patients out of the initial zones of the disease.

According to recent data, about 400 patients would be followed in the Belgian hospitals, and about 1 in 1500 newborns in Belgium would be a major carrier of hemoglobinopathies. The most expressive and most frequent complication of the disease is vaso-occlusive crisis, dominated by a painful syndrome. In addition to vaso-occlusive crises, many more chronic biological disturbances are observed in sickle cell patients. Their contribution to the course of the disease is becoming increasingly stressing. Among them are intravascular hemolysis, hyper-adhesion of blood cells to vascular endothelium, inflammation, oxidative stress, vasculopathy and bleeding disorders.

Sickle cell disease is considered nowadays as a hypercoagulable state. Indeed, sickle cell patients have a high risk of non-hemorrhagic stroke, thrombosis in the pulmonary arteries and deep vein thrombosis that are otherwise associated with mortality and high morbidity. Many anomalies at various levels in the hemostatic system demonstrate coagulation activation even in clinically stable condition.

However, the approach used so far to the measure of clotting in sickle cell disease was segmented in the sense that the various components of the hemostatic balance were studied separately. This scale is complex, this approach difficult to give a comprehensive and integrated picture of the various disturbances in the system. The thrombin generation test is a functional test which explores the coagulation globally, integrating both pro players that anticoagulants actors in the system. The investigators have used this test to demonstrate that the hemostatic potential was high in a cohort of affected children compared to control children of the same age. In this cohort high hemostatic potential was related to the rate of circulating microparticles and intravascular hemolysis rate. Studies are underway to look for correlations between the hemostatic potential and clinical complications in this pediatric cohort.

The use of thrombin generation test for the study of hemostasis in adult patients with sickle cell disease, and the contribution of coagulation disorders with the occurrence of complications of the disease remain little known. The investigators will therefore:

  • Characterize the hemostatic potential of adult sickle cell patients followed at the CHU Brugmann
  • Search for links between the hemostatic potential and other biological phenomena observed during the disease (intravascular hemolysis, microparticles, vasculopathy, inflammation)
  • Search for correlations with clinical complications
  • Evaluate the effect of treatment (including exchange transfusions) on the hemostatic potential.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Sickle Cell Disease
Intervention  ICMJE
  • Other: Blood sampling - healthy volunteers
    Four citrate blood sampling tubes (blue cap, 2.7ml) will be taken only once.
  • Other: Blood sampling - sickle cell patients arm - stable condition
    Four citrate blood sampling tubes (blue cap, 2.7ml) will be taken only once.
  • Other: Blood sampling - sickle cell patients arm- exsanguinotransfusion needed
    Four citrate blood sampling tubes (blue cap, 2.7ml) will be taken only once, before and after the exsanguinotransfusion.
  • Other: Blood sampling - sickle cell patients arm - vaso-occlusive crisis.
    Four citrate blood sampling tubes (blue cap, 2.7ml) will be taken only once.
Study Arms  ICMJE
  • Experimental: Sickle cell disease
    This arm will include an approximate number of 50 sickle cell disease patients, homozygous and heterozygous.
    Interventions:
    • Other: Blood sampling - sickle cell patients arm - stable condition
    • Other: Blood sampling - sickle cell patients arm- exsanguinotransfusion needed
    • Other: Blood sampling - sickle cell patients arm - vaso-occlusive crisis.
  • Control
    This arm will include an approximate number of 30 healthy volunteers.
    Intervention: Other: Blood sampling - healthy volunteers
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 25, 2016)
64
Original Estimated Enrollment  ICMJE
 (submitted: September 30, 2015)
80
Actual Study Completion Date  ICMJE July 2016
Actual Primary Completion Date July 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

- Sickle cell disease group: Sickle cell disease patients aged over 18 years

- Healthy volunteers group: Healthy volunteers, age matching with the sickle cell disease group

Exclusion Criteria:

- Sickle cell disease group: Pregnant women, dialysis patients, patients with an hepatic impairment, patients under treatments that can interfere with coagulation

- Healthy volunteers group: Pregnant women, known chronical disease, acute inflammatory syndrome, hemostasis disorder, abnormal complete blood count

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02565082
Other Study ID Numbers  ICMJE CHUB-Drepanocytose-Hemostatic
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dr Anne Demulder, Brugmann University Hospital
Study Sponsor  ICMJE Brugmann University Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Anne Demulder, MD CHU Brugmann
Principal Investigator: Bhavna Mahadeb St Pierre Hospital
PRS Account Brugmann University Hospital
Verification Date July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP