Clinical trial NCT00784082: Inflammatory Response to Hydroxyurea Therapy in Sickle Cell Disease
Official title: Inflammatory Response to Hydroxyurea Therapy in Sickle Cell Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sickle Cell Disease
Keywords: Sickle cell disease, hydroxyurea, inflammation
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2008-11-02
Enrollment: 62
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Homozygous SS sickle cell children, aged \> 3 years, of sub-Saharian Africa heterozygous AS parents or siblings of the patients, and AA siblings or healthy African unrelated subjects, aged \> 3 years

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).

Eligibility criteria: 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

Primary outcomes:
measure: Determination of plasma inflammatory markers
timeFrame: Day 1
Secondary outcomes:
measure: Clinical data
timeFrame: Day 1
measure: Hematological at baseline
timeFrame: Day 1
measure: Determination of HbF
timeFrame: Day 1
measure: Determination of markers of the "acute phase"
timeFrame: Day 1
measure: Plasma concentrations
timeFrame: Day 1
Other outcomes:
Locations:
city: Colombes
country: France
facility: Hopital Louis Mourier
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Marie-Hélène Odièvre, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: