Sickle Cell Disease
Conditions
Keywords
Sickle cell disease, hydroxyurea, inflammation
Brief summary
In sickle cell disease (SCD), polymerisation of haemoglobin S and the resulting shape change of the red blood cells (RBC) lead to vascular occlusion and severe painful crises. Permanent inflammatory state and abnormal RBC adhesion to the endothelium trigger these phenomenon. Hydroxyurea (HU) is the only drug that has been shown to reduce clinical severity of SCD, and this was initially attributed to the stimulation of foetal haemoglobin (HbF). However, the clinical response does not correlate consistently with the degree and time of HbF increment, suggesting that HU clinical benefits may involve other mechanisms such as the induction of natural anti-inflammatory response via the hypothalami-pituitary-adrenal axis.
Detailed description
Plasmatic proinflammatory molecules (C-reactive protein, orosomucoid, RANTES, IL-6, IL-8, MCP-1, IL-1A, IL-1B, ET-1, IL-4, IL-10, TNFalpha, IFNgamma), hormones from the hypothalami-pituitary-adrenal axis (cortisol, ACTH), and hypothalamic peptids (arginine vasopressin, corticotrophin-releasing hormone) will be measured from SCD children treated or not with HU (20 treated children, 20 untreated children with a history of vaso-occlusive events, 20 asymptomatic children, and 20 healthy African controls).
Interventions
DRUGHydroxycarbamide, Hydroxyurea (drug)
hydroxyurea 20-25 mg/kg/day since at least 3 months
Sponsors
Assistance Publique - Hôpitaux de Paris
Eligibility
Sex/Gender
ALL
Age
3 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Homozygous SS sickle cell children, aged \> 3 years, of sub-Saharian Africa extraction, in a steady-state of disease (free of any infectious or vaso-occlusive events for the 4 weeks prior to and 2 weeks after blood sampling, and transfusion-free for 4 months prior to blood sampling), taken no drug except penicillin-V, folate or iron supplementation, hydroxyurea, divided into three groups : * children treated with hydroxyurea 20-25 mg/kg/day since at least 3 months with clinical efficacy on vaso-occlusive events * untreated children with major vaso-occlusive events * children \> 5 year-old without a history of vaso-occlusive events Signed informed consent obtained from the subjects (if possible) and their parents 2. Controls : heterozygous AS parents or siblings of the patients, and AA siblings or healthy African unrelated subjects, aged \> 3 years, taken no drug on the day of blood sampling. Signed informed consent obtained from the subjects (if possible) and their parents
Exclusion criteria
* Children in a acute-phase of the disease * Parent's or patient's refusal * Taking any drug except penicillin-V, folate or iron supplementation, hydroxyurea * Un-healthy control or taking drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determination of plasma inflammatory markers | Day 1 | Determination of plasma inflammatory markers (RANTES, IL-6, IL-8, MCP-1, IL-1A, IL-1B, ET-1, IL-4, IL-10, TNF a,, IFN g) of hormones of the pituitary-adrenal (cortisol, ACTH) and hypothalamic peptides (AVP, CRH). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical data | Day 1 | Clinical data (age, sex of the patient and his parent or siblings, frequency of painful crises requiring hospitalization, measured / year in the three years prior to the study, frequency and causes acute anemic episodes, whether or not a hepatosplenomegaly) |
| Hematological at baseline | Day 1 | Hematological at baseline (Hb, reticulocytes, MCV, platelets, leukocytes, PN and monocytes, lymphocytes, erythroblasts, iron status) |
| Determination of HbF | Day 1 | Determination of HbF |
| Determination of markers of the acute phase | Day 1 | Determination of markers of the acute phase: CRP and orosomucoid |
| Plasma concentrations | Day 1 | Plasma concentrations of HU just before taking HU (residual) and H2 after dosing. |
Countries
France
Outcome results
None listed