Study of Biological Markers in Children With Sickle Cell Disease

Study Overview
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Brief Summary
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Sickle cell disease is associated with significant morbi-mortality hence the interest in an early and targeted care. At present, there is no plasmatic marker able to identify infants at higher risk of developping severe complications later in life. However, recent studies have demonstrated a correlation between certain complications of the disease and biomarkers of the endothelial dysfunction characterizing it. Investigators prospectively followed a cohort of children diagnosed with SCD through the universal neonatal screening using inflammatory and haemostatic plasmatic markers to study their annual evolution. Investigators then will evaluate potential associations between these biological markers and the occurrence of SCD related complications. A secondary objective of this study is to evaluate the repercussions of therapeutic intervention on these markers. .

Official Title
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Prospective Clinical Study on Early Inflammatory, Cell Adhesion and Hemostatic Plasmatic Markers of Endothelial Dysfunction in Children With Sickle Cell Disease (SCD)

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Other: Blood sampling
* Other: Blood sampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient aged less than 6 months Sickle cell syndrome SS, Sβthal or SC confirmed by hemoglobin electrophoresis Subjects legal representatives must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to let participate their child in the study Exclusion Criteria: Congenital abnormality other than sickle cell disease except for a glucose-6-phosphate-deshydrogenase Prematurity Initiation of the following therapies before enrollment: chronic transfusion regimen or bone marrow transplantation

Ages Eligible for Study
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Minimum Age: 6 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SCD Patient<br> | Other: Blood sampling<br>* Blood sampling at the age of 6 and 12 months, 2-3-4 years<br>Other: Blood sampling<br>* Blood sampling before any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasmatic levels of IL-6 at 12 months of age | Measurement of plasmatic levels of IL-6 (fg/mL) by flow cytometric assay | 12 months of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasmatic levels of IL-6 at 6 months of age | Measurement of plasmatic levels of IL-6 (fg/mL) by flow cytometric assay | 6 months of age | 
| Plasmatic levels of IL-6 at 2 years of age | Measurement of plasmatic levels of IL-6 (fg/mL) by flow cytometric assay | 2 years of age | 
| Plasmatic levels of IL-6 at 3 years of age | Measurement of plasmatic levels of IL-6 (fg/mL) by flow cytometric assay | 3 years of age | 
| Plasmatic levels of IL-6 at 4 years of age | Measurement of plasmatic levels of IL-6 (fg/mL) by flow cytometric assay | 4 years of age | 
| Plasmatic levels of IL-6 before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres | Measurement of plasmatic levels of IL-6 (fg/mL) by flow cytometric assay | Before the introduction of any new sickle cell disease treatment | 
| Plasmatic levels of IL-1ß at 6 months of age | Measurement of plasmatic levels of IL-1ß (fg/mL) by flow cytometric assay | 6 months of age | 
| Plasmatic levels of IL-1ß at 12 months of age | Measurement of plasmatic levels of IL-1ß (fg/mL) by flow cytometric assay | 12 months of age | 
| Plasmatic levels of IL-1ß at 2 years of age | Measurement of plasmatic levels of IL-1ß (fg/mL) by flow cytometric assay | 2 years of age | 
| Plasmatic levels of IL-1ß at 3 years of age | Measurement of plasmatic levels of IL-1ß (fg/mL) by flow cytometric assay | 3 years of age | 
| Plasmatic levels of IL-1ß at 4 years of age | Measurement of plasmatic levels of IL-1ß (fg/mL) by flow cytometric assay | 4 years of age | 
| Plasmatic levels of IL-1ß before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres | Measurement of plasmatic levels of IL-1ß (fg/mL) by flow cytometric assay | Before the introduction of any new sickle cell disease treatment | 
| Plasmatic levels of IL-8 at 6 months of age | Measurement of plasmatic levels of IL-8 (fg/mL) by flow cytometric assay | 6 months of age | 
| Plasmatic levels of IL-8 at 12 months of age | Measurement of plasmatic levels of IL-8 (fg/mL) by flow cytometric assay | 12 months of age | 
| Plasmatic levels of IL-8 at 2 years of age | Measurement of plasmatic levels of IL-8 (fg/mL) by flow cytometric assay | 2 years of age | 
| Plasmatic levels of IL-8 at 3 years of age | Measurement of plasmatic levels of IL-8 (fg/mL) by flow cytometric assay | 3 years of age | 
| Plasmatic levels of IL-8 at 4 years of age | Measurement of plasmatic levels of IL-8 (fg/mL) by flow cytometric assay | 4 years of age | 
| Plasmatic levels of IL-8 before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres | Measurement of plasmatic levels of IL-8 (fg/mL) by flow cytometric assay | Before the introduction of any new sickle cell disease treatment | 
| Plasmatic levels of IL-10 at 6 months of age | Measurement of plasmatic levels of IL-10 (fg/mL) by flow cytometric assay | 6 months of age | 
| Plasmatic levels of IL-10 at 12 months of age | Measurement of plasmatic levels of IL-10 (fg/mL) by flow cytometric assay | 12 months of age | 
| Plasmatic levels of IL-10 at 2 years of age | Measurement of plasmatic levels of IL-10 (fg/mL) by flow cytometric assay | 2 years of age | 
| Plasmatic levels of IL-10 at 3 years of age | Measurement of plasmatic levels of IL-10 (fg/mL) by flow cytometric assay | 3 years of age | 
| Plasmatic levels of IL-10 at 4 years of age | Measurement of plasmatic levels of IL-10 (fg/mL) by flow cytometric assay | 4 years of age | 
| Plasmatic levels of IL-10 before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres | Measurement of plasmatic levels of IL-10 (fg/mL) by flow cytometric assay | Before the introduction of any new sickle cell disease treatment | 
| Plasmatic levels of IL-12 at 6 months of age | Measurement of plasmatic levels of IL-12 (fg/mL) by flow cytometric assay | 6 months of age | 
| Plasmatic levels of IL-12 at 12 months of age | Measurement of plasmatic levels of IL-12 (fg/mL) by flow cytometric assay | 12 months of age | 
| Plasmatic levels of IL-12 at 2 years of age | Measurement of plasmatic levels of IL-12 (fg/mL) by flow cytometric assay | 2 years of age | 
| Plasmatic levels of IL-12 at 3 years of age | Measurement of plasmatic levels of IL-12 (fg/mL) by flow cytometric assay | 3 years of age | 
| Plasmatic levels of IL-12 at 4 years of age | Measurement of plasmatic levels of IL-12 (fg/mL) by flow cytometric assay | 4 years of age | 
| Plasmatic levels of IL-12 before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres | Measurement of plasmatic levels of IL-12 (fg/mL) by flow cytometric assay | Before the introduction of any new sickle cell disease treatment | 
| Plasmatic levels of TNF alpha at 6 months of age | Measurement of plasmatic levels of TNF alpha (fg/mL) by flow cytometric assay | 6 months of age | 
| Plasmatic levels of TNF alpha at 12 months of age | Measurement of plasmatic levels of TNF alpha (fg/mL) by flow cytometric assay | 12 months of age | 
| Plasmatic levels of TNF alpha at 2 years of age | Measurement of plasmatic levels of TNF alpha (fg/mL) by flow cytometric assay | 2 years of age | 
| Plasmatic levels of TNF alpha at 3 years of age | Measurement of plasmatic levels of TNF alpha (fg/mL) by flow cytometric assay | 3 years of age | 
| Plasmatic levels of TNF alpha at 4 years of age | Measurement of plasmatic levels of TNF alpha (fg/mL) by flow cytometric assay | 4 years of age | 
| Plasmatic levels of TNF alpha before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres | Measurement of plasmatic levels of TNF alpha (fg/mL) by flow cytometric assay | Before the introduction of any new sickle cell disease treatment | 
| Plasmatic levels of ICAM-1 at 6 months of age | Measurement of plasmatic levels of ICAM-1 (pg/mL) by flow cytometric assay | 6 months of age | 
| Plasmatic levels of ICAM-1 at 12 months of age | Measurement of plasmatic levels of ICAM-1 (pg/mL) by flow cytometric assay | 12 months of age | 
| Plasmatic levels of ICAM-1 at 2 years of age | Measurement of plasmatic levels of ICAM-1 (pg/mL) by flow cytometric assay | 2 years of age | 
| Plasmatic levels of ICAM-1 at 3 years of age | Measurement of plasmatic levels of ICAM-1 (pg/mL) by flow cytometric assay | 3 years of age | 
| Plasmatic levels of ICAM-1 at 4 years of age | Measurement of plasmatic levels of ICAM-1 (pg/mL) by flow cytometric assay | 4 years of age | 
| Plasmatic levels of ICAM-1 before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres | Measurement of plasmatic levels of ICAM-1 (pg/mL) by flow cytometric assay | Before the introduction of any new sickle cell disease treatment | 
| Plasmatic levels of VCAM-1 at 6 months of age | Measurement of plasmatic levels of VCAM-1 (pg/mL) by flow cytometric assay | 6 months of age | 
| Plasmatic levels of VCAM-1 at 12 months of age | Measurement of plasmatic levels of VCAM-1 (pg/mL) by flow cytometric assay | 12 months of age | 
| Plasmatic levels of VCAM-1 at 2 years of age | Measurement of plasmatic levels of VCAM-1 (pg/mL) by flow cytometric assay | 2 years of age | 
| Plasmatic levels of VCAM-1 at 3 years of age | Measurement of plasmatic levels of VCAM-1 (pg/mL) by flow cytometric assay | 3 years of age | 
| Plasmatic levels of VCAM-1 at 4 years of age | Measurement of plasmatic levels of VCAM-1 (pg/mL) by flow cytometric assay | 4 years of age | 
| Plasmatic levels of VCAM-1 before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres | Measurement of plasmatic levels of VCAM-1 (pg/mL) by flow cytometric assay | Before the introduction of any new sickle cell disease treatment | 
| Plasmatic VCAM-1 levels after in vitro stimulation with LPS | Measurement of plasmatic levels of VCAM-1 (pg/mL) by flow cytometric assay after in vitro stimulation with LPS | Plasmatic level of VCAM-1 after in vitro stimulation with LPS | 
| Plasmatic levels of E-selectine at 6 months of age | Measurement of plasmatic levels of E-selectine (pg/mL) by flow cytometric assay | 6 months of age | 
| Plasmatic levels of E-selectine at 12 months of age | Measurement of plasmatic levels of E-selectine (pg/mL) by flow cytometric assay | 12 months of age | 
| Plasmatic levels of E-selectine at 2 years of age | Measurement of plasmatic levels of E-selectine (pg/mL) by flow cytometric assay | 2 years of age | 
| Plasmatic levels of E-selectine at 3 years of age | Measurement of plasmatic levels of E-selectine (pg/mL) by flow cytometric assay | 3 years of age | 
| Plasmatic levels of E-selectine at 4 years of age | Measurement of plasmatic levels of E-selectine (pg/mL) by flow cytometric assay | 4 years of age | 
| Plasmatic levels of E-selectine before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres | Measurement of plasmatic levels of E-selectine (pg/mL) by flow cytometric assay | Before the introduction of any new sickle cell disease treatment | 
| Plasmatic levels of P-selectine at 6 months of age | Measurement of plasmatic levels of P-selectine (pg/mL) by flow cytometric assay | 6 months of age | 
| Plasmatic levels of P-selectine at 12 months of age | Measurement of plasmatic levels of P-selectine (pg/mL) by flow cytometric assay | 12 months of age | 
| Plasmatic levels of P-selectine at 2 years of age | Measurement of plasmatic levels of P-selectine (pg/mL) by flow cytometric assay | 2 years of age | 
| Plasmatic levels of P-selectine at 3 years of age | Measurement of plasmatic levels of P-selectine (pg/mL) by flow cytometric assay | 3 years of age | 
| Plasmatic levels of P-selectine at 4 years of age | Measurement of plasmatic levels of P-selectine (pg/mL) by flow cytometric assay | 4 years of age | 
| Plasmatic levels of P-selectine before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres | Measurement of plasmatic levels of P-selectine (pg/mL) by flow cytometric assay | Before the introduction of any new sickle cell disease treatment | 
| Plasmatic levels of Vascular Endothelial Growth Factor (VEGF) at 6 months of age | Measurement of plasmatic levels of VEGF (pg/mL) by flow cytometric assay | 6 months of age | 
| Plasmatic levels of Vascular Endothelial Growth Factor (VEGF) at 12 months of age | Measurement of plasmatic levels of VEGF (pg/mL) by flow cytometric assay | 12 months of age | 
| Plasmatic levels of Vascular Endothelial Growth Factor (VEGF) at 2 years of age | Measurement of plasmatic levels of VEGF (pg/mL) by flow cytometric assay | 2 years of age | 
| Plasmatic levels of Vascular Endothelial Growth Factor (VEGF) at 3 years of age | Measurement of plasmatic levels of VEGF (pg/mL) by flow cytometric assay | 3 years of age | 
| Plasmatic levels of Vascular Endothelial Growth Factor (VEGF) at 4 years of age | Measurement of plasmatic levels of VEGF (pg/mL) by flow cytometric assay | 4 years of age | 
| Plasmatic levels of VEGF before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres | Measurement of plasmatic levels of VEGF (pg/mL) by flow cytometric assay | Before the introduction of any new sickle cell disease treatment | 
| Lag time parameter in thrombin generation assay at 6 months of age | Measurement of lag time (minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method. | 6 months of age | 
| Lag time parameter in thrombin generation assay at 12 months of age | Measurement of lag time (minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method. | 12 months of age | 
| Lag time parameter in thrombin generation assay at 2 years of age | Measurement of lag time (minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method. | 2 years of age | 
| Lag time parameter in thrombin generation assay at 3 years of age | Measurement of lag time (minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method. | 3 years of age | 
| Lag time parameter in thrombin generation assay at 4 years of age | Measurement of lag time (minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method. | 4 years of age | 
| Lag time parameter in thrombin generation assay before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres | Measurement of lag time (minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method. | Before the introduction of any new sickle cell disease treatment | 
| Peak height parameter in thrombin generation assay at 6 months of age | Measurement of peak height (nM) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method. | 6 months of age | 
| Peak height parameter in thrombin generation assay at 12 months of age | Measurement of peak height (nM) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method. | 12 months of age | 
| Peak height parameter in thrombin generation assay at 2 years of age | Measurement of peak height (nM) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method. | 2 years of age | 
| Peak height parameter in thrombin generation assay at 3 years of age | Measurement of peak height (nM) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method. | 3 years of age | 
| Peak height parameter in thrombin generation assay at 4 years of age | Measurement of peak height (nM) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method. | 4 years of age | 
| Peak height parameter in thrombin generation assay before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres | Measurement of peak height (nM) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method. | Before the introduction of any new sickle cell disease treatment | 
| Time to peak parameter in thrombin generation assay at 6 months of age | Measurement of time to peak (minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method | 6 months of age | 
| Time to peak parameter in thrombin generation assay at 12 months of age | Measurement of time to peak (minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method | 12 months of age | 
| Time to peak parameter in thrombin generation assay at 2 years of age | Measurement of time to peak (minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method | 2 years of age | 
| Time to peak parameter in thrombin generation assay at 3 years of age | Measurement of time to peak (minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method | 3 years of age | 
| Time to peak parameter in thrombin generation assay at 4 years of age | Measurement of time to peak (minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method | 4 years of age | 
| Time to peak parameter in thrombin generation assay before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres | Measurement of time to peak (minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method | Before the introduction of any new sickle cell disease treatment | 
| Endogenous thrombin potential parameter in thrombin generation assay at 6 months of age | Measurement of endogenous thrombin potential (nM x minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method. | 6 months of age | 
| Endogenous thrombin potential parameter in thrombin generation assay at 12 months of age | Measurement of endogenous thrombin potential (nM x minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method. | 12 months of age | 
| Endogenous thrombin potential parameter in thrombin generation assay at 2 years of age | Measurement of endogenous thrombin potential (nM x minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method. | 2 years of age | 
| Endogenous thrombin potential parameter in thrombin generation assay at 3 years of age | Measurement of endogenous thrombin potential (nM x minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method. | 3 years of age | 
| Endogenous thrombin potential parameter in thrombin generation assay at 4 years of age | Measurement of endogenous thrombin potential (nM x minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method. | 4 years of age | 
| Endogenous thrombin potential parameter in thrombin generation assay before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres | Measurement of endogenous thrombin potential (nM x minutes) parameter of thrombin generation in platelet poor plasma using the Calibrated Automated Thrombogram (CAT®) method. | before the introduction of any new sickle cell disease treatment | 
| Plasmatic levels of Factor VIII at 6 months of age | Measurement of plasmatic levels of Factor VIII by flow cytometric assay | 6 months of age | 
| Plasmatic levels of Factor VIII at 12 months of age | Measurement of plasmatic levels of Factor VIII by flow cytometric assay | 12 months of age | 
| Plasmatic levels of Factor VIII at 2 years of age | Measurement of plasmatic levels of Factor VIII by flow cytometric assay | 2 years of age | 
| Plasmatic levels of Factor VIII at 3 years of age | Measurement of plasmatic levels of Factor VIII by flow cytometric assay | 3 years of age | 
| Plasmatic levels of Factor VIII at 4 years of age | Measurement of plasmatic levels of Factor VIII by flow cytometric assay | 4 years of age | 
| Plasmatic levels of Factor VIII before the introduction of any new sickle cell disease treatment as determined by a physician according to the standard of care to which the hospital adheres | Measurement of plasmatic levels of Factor VIII by flow cytometric assay | Before the introduction of any new sickle cell disease treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sickle cell disease, children, thrombin generation, inflammation, cytokines, adhesion molecules, plasmatic markers, coagulation