Clinical trial NCT04839159: Study of Biological Markers in Children With Sickle Cell Disease
Official title: Prospective Clinical Study on Early Inflammatory, Cell Adhesion and Hemostatic Plasmatic Markers of Endothelial Dysfunction in Children With Sickle Cell Disease (SCD)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Sickle Cell Disease
Keywords: Sickle cell disease, children, thrombin generation, inflammation, cytokines, adhesion molecules, plasmatic markers, coagulation
Lead sponsor: Queen Fabiola Children's University Hospital
Sponsor class: OTHER
First posted: 2021-04-09
Enrollment: 41
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.

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Eligibility criteria: 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

Primary outcomes:
measure: Plasmatic levels of IL-6 at 12 months of age
timeFrame: 12 months of age
Secondary outcomes:
measure: Plasmatic levels of IL-6 at 6 months of age
timeFrame: 6 months of age
measure: Plasmatic levels of IL-6 at 2 years of age
timeFrame: 2 years of age
measure: Plasmatic levels of IL-6 at 3 years of age
timeFrame: 3 years of age
measure: Plasmatic levels of IL-6 at 4 years of age
timeFrame: 4 years of age
measure: 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
timeFrame: Before the introduction of any new sickle cell disease treatment
measure: Plasmatic levels of IL-1ß at 6 months of age
timeFrame: 6 months of age
measure: Plasmatic levels of IL-1ß at 12 months of age
timeFrame: 12 months of age
measure: Plasmatic levels of IL-1ß at 2 years of age
timeFrame: 2 years of age
measure: Plasmatic levels of IL-1ß at 3 years of age
timeFrame: 3 years of age
measure: Plasmatic levels of IL-1ß at 4 years of age
timeFrame: 4 years of age
measure: 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
timeFrame: Before the introduction of any new sickle cell disease treatment
measure: Plasmatic levels of IL-8 at 6 months of age
timeFrame: 6 months of age
measure: Plasmatic levels of IL-8 at 12 months of age
timeFrame: 12 months of age
measure: Plasmatic levels of IL-8 at 2 years of age
timeFrame: 2 years of age
measure: Plasmatic levels of IL-8 at 3 years of age
timeFrame: 3 years of age
measure: Plasmatic levels of IL-8 at 4 years of age
timeFrame: 4 years of age
measure: 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
timeFrame: Before the introduction of any new sickle cell disease treatment
measure: Plasmatic levels of IL-10 at 6 months of age
timeFrame: 6 months of age
measure: Plasmatic levels of IL-10 at 12 months of age
timeFrame: 12 months of age
measure: Plasmatic levels of IL-10 at 2 years of age
timeFrame: 2 years of age
measure: Plasmatic levels of IL-10 at 3 years of age
timeFrame: 3 years of age
measure: Plasmatic levels of IL-10 at 4 years of age
timeFrame: 4 years of age
measure: 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
timeFrame: Before the introduction of any new sickle cell disease treatment
measure: Plasmatic levels of IL-12 at 6 months of age
timeFrame: 6 months of age
measure: Plasmatic levels of IL-12 at 12 months of age
timeFrame: 12 months of age
measure: Plasmatic levels of IL-12 at 2 years of age
timeFrame: 2 years of age
measure: Plasmatic levels of IL-12 at 3 years of age
timeFrame: 3 years of age
measure: Plasmatic levels of IL-12 at 4 years of age
timeFrame: 4 years of age
measure: 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
timeFrame: Before the introduction of any new sickle cell disease treatment
measure: Plasmatic levels of TNF alpha at 6 months of age
timeFrame: 6 months of age
measure: Plasmatic levels of TNF alpha at 12 months of age
timeFrame: 12 months of age
measure: Plasmatic levels of TNF alpha at 2 years of age
timeFrame: 2 years of age
measure: Plasmatic levels of TNF alpha at 3 years of age
timeFrame: 3 years of age
measure: Plasmatic levels of TNF alpha at 4 years of age
timeFrame: 4 years of age
measure: 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
timeFrame: Before the introduction of any new sickle cell disease treatment
measure: Plasmatic levels of ICAM-1 at 6 months of age
timeFrame: 6 months of age
measure: Plasmatic levels of ICAM-1 at 12 months of age
timeFrame: 12 months of age
measure: Plasmatic levels of ICAM-1 at 2 years of age
timeFrame: 2 years of age
measure: Plasmatic levels of ICAM-1 at 3 years of age
timeFrame: 3 years of age
measure: Plasmatic levels of ICAM-1 at 4 years of age
timeFrame: 4 years of age
measure: 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
timeFrame: Before the introduction of any new sickle cell disease treatment
measure: Plasmatic levels of VCAM-1 at 6 months of age
timeFrame: 6 months of age
measure: Plasmatic levels of VCAM-1 at 12 months of age
timeFrame: 12 months of age
measure: Plasmatic levels of VCAM-1 at 2 years of age
timeFrame: 2 years of age
measure: Plasmatic levels of VCAM-1 at 3 years of age
timeFrame: 3 years of age
measure: Plasmatic levels of VCAM-1 at 4 years of age
timeFrame: 4 years of age
measure: 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
timeFrame: Before the introduction of any new sickle cell disease treatment
measure: Plasmatic VCAM-1 levels after in vitro stimulation with LPS
timeFrame: Plasmatic level of VCAM-1 after in vitro stimulation with LPS
measure: Plasmatic levels of E-selectine at 6 months of age
timeFrame: 6 months of age
measure: Plasmatic levels of E-selectine at 12 months of age
timeFrame: 12 months of age
measure: Plasmatic levels of E-selectine at 2 years of age
timeFrame: 2 years of age
measure: Plasmatic levels of E-selectine at 3 years of age
timeFrame: 3 years of age
measure: Plasmatic levels of E-selectine at 4 years of age
timeFrame: 4 years of age
measure: 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
timeFrame: Before the introduction of any new sickle cell disease treatment
measure: Plasmatic levels of P-selectine at 6 months of age
timeFrame: 6 months of age
measure: Plasmatic levels of P-selectine at 12 months of age
timeFrame: 12 months of age
measure: Plasmatic levels of P-selectine at 2 years of age
timeFrame: 2 years of age
measure: Plasmatic levels of P-selectine at 3 years of age
timeFrame: 3 years of age
measure: Plasmatic levels of P-selectine at 4 years of age
timeFrame: 4 years of age
measure: 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
timeFrame: Before the introduction of any new sickle cell disease treatment
measure: Plasmatic levels of Vascular Endothelial Growth Factor (VEGF) at 6 months of age
timeFrame: 6 months of age
measure: Plasmatic levels of Vascular Endothelial Growth Factor (VEGF) at 12 months of age
timeFrame: 12 months of age
measure: Plasmatic levels of Vascular Endothelial Growth Factor (VEGF) at 2 years of age
timeFrame: 2 years of age
measure: Plasmatic levels of Vascular Endothelial Growth Factor (VEGF) at 3 years of age
timeFrame: 3 years of age
measure: Plasmatic levels of Vascular Endothelial Growth Factor (VEGF) at 4 years of age
timeFrame: 4 years of age
measure: 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
timeFrame: Before the introduction of any new sickle cell disease treatment
measure: Lag time parameter in thrombin generation assay at 6 months of age
timeFrame: 6 months of age
measure: Lag time parameter in thrombin generation assay at 12 months of age
timeFrame: 12 months of age
measure: Lag time parameter in thrombin generation assay at 2 years of age
timeFrame: 2 years of age
measure: Lag time parameter in thrombin generation assay at 3 years of age
timeFrame: 3 years of age
measure: Lag time parameter in thrombin generation assay at 4 years of age
timeFrame: 4 years of age
measure: 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
timeFrame: Before the introduction of any new sickle cell disease treatment
measure: Peak height parameter in thrombin generation assay at 6 months of age
timeFrame: 6 months of age
measure: Peak height parameter in thrombin generation assay at 12 months of age
timeFrame: 12 months of age
measure: Peak height parameter in thrombin generation assay at 2 years of age
timeFrame: 2 years of age
measure: Peak height parameter in thrombin generation assay at 3 years of age
timeFrame: 3 years of age
measure: Peak height parameter in thrombin generation assay at 4 years of age
timeFrame: 4 years of age
measure: 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
timeFrame: Before the introduction of any new sickle cell disease treatment
measure: Time to peak parameter in thrombin generation assay at 6 months of age
timeFrame: 6 months of age
measure: Time to peak parameter in thrombin generation assay at 12 months of age
timeFrame: 12 months of age
measure: Time to peak parameter in thrombin generation assay at 2 years of age
timeFrame: 2 years of age
measure: Time to peak parameter in thrombin generation assay at 3 years of age
timeFrame: 3 years of age
measure: Time to peak parameter in thrombin generation assay at 4 years of age
timeFrame: 4 years of age
measure: 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
timeFrame: Before the introduction of any new sickle cell disease treatment
measure: Endogenous thrombin potential parameter in thrombin generation assay at 6 months of age
timeFrame: 6 months of age
measure: Endogenous thrombin potential parameter in thrombin generation assay at 12 months of age
timeFrame: 12 months of age
measure: Endogenous thrombin potential parameter in thrombin generation assay at 2 years of age
timeFrame: 2 years of age
measure: Endogenous thrombin potential parameter in thrombin generation assay at 3 years of age
timeFrame: 3 years of age
measure: Endogenous thrombin potential parameter in thrombin generation assay at 4 years of age
timeFrame: 4 years of age
measure: 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
timeFrame: before the introduction of any new sickle cell disease treatment
measure: Plasmatic levels of Factor VIII at 6 months of age
timeFrame: 6 months of age
measure: Plasmatic levels of Factor VIII at 12 months of age
timeFrame: 12 months of age
measure: Plasmatic levels of Factor VIII at 2 years of age
timeFrame: 2 years of age
measure: Plasmatic levels of Factor VIII at 3 years of age
timeFrame: 3 years of age
measure: Plasmatic levels of Factor VIII at 4 years of age
timeFrame: 4 years of age
measure: 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
timeFrame: Before the introduction of any new sickle cell disease treatment
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: CHU Saint Pierre
city: Brussels
country: Belgium
facility: Hôpital Universitaire Des Enfants Reine Fabiola
city: Brussels
country: Belgium
facility: HIS - Site Etterbeek-Ixelles
Study officials:
affiliation: Queen Fabiola Children's University Hospital
name: Bushra Zucca, MD
role: PRINCIPAL_INVESTIGATOR
References:
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