Inflammatory Response to Hydroxyurea Therapy in Sickle Cell Disease

Completed

• Conditions: Sickle Cell Disease
• Interventions: Drug: Hydroxycarbamide, Hydroxyurea (drug)

• Registration Number: NCT00784082
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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).

Study Timeline

• Study First Submitted: 2008-10-27
• Study First Submitted QC: 2008-10-31
• Study First Posted: 2008-11-02
• Study Start: 2009-05
• Primary Completion: 2012-10
• Study Completion: 2012-11
• Status Verified: 2013-01
• Last Update Submitted: 2013-01-30
• Last Update Posted: 2013-01-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 62

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Homozygous SS children	Hydroxycarbamide, Hydroxyurea (drug)	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.
Homozygous SS sickle cell children	Hydroxycarbamide, Hydroxyurea (drug)	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Determination of markers of the "acute phase"	Day 1	Determination of markers of the "acute phase": CRP and orosomucoid
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)
Determination of HbF	Day 1	Determination of HbF
Hematological at baseline	Day 1	Hematological at baseline (Hb, reticulocytes, MCV, platelets, leukocytes, PN and monocytes, lymphocytes, erythroblasts, iron status)
Plasma concentrations	Day 1	Plasma concentrations of HU just before taking HU (residual) and H2 after dosing.

Trial Locations

Locations (1)

Hopital Louis Mourier; 🇫🇷 Colombes, France