Inflammatory Response to Hydroxyurea Therapy in Sickle Cell Disease
Overview
- Phase
- Not Applicable
- Intervention
- Hydroxycarbamide, Hydroxyurea (drug)
- Conditions
- Sickle Cell Disease
- Sponsor
- Assistance Publique - Hôpitaux de Paris
- Enrollment
- 62
- Locations
- 1
- Primary Endpoint
- Determination of plasma inflammatory markers
- Status
- Completed
- Last Updated
- 13 years ago
Overview
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Homozygous SS sickle cell children
Hydroxycarbamide, Hydroxyurea (drug): 1. Homozygous SS sickle cell children, aged \> 3 years, of sub-Saharian Africa extraction, in a steady-state of disease , 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 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.
Intervention: Hydroxycarbamide, Hydroxyurea (drug)
Homozygous SS children
Hydroxycarbamide, Hydroxyurea (drug): 1. Homozygous SS children, aged \> 3 years, of sub-Saharian Africa extraction, in a steady-state of disease, 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 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.
Intervention: Hydroxycarbamide, Hydroxyurea (drug)
Outcomes
Primary Outcomes
Determination of plasma inflammatory markers
Time Frame: 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 Outcomes
- Clinical data(Day 1)
- Determination of HbF(Day 1)
- Hematological at baseline(Day 1)
- Plasma concentrations(Day 1)
- Determination of markers of the "acute phase"(Day 1)