Inflammatory Response to Hydroxyurea Therapy in Sickle Cell Disease

Sickle Cell Disease Clinical Trial

Official title:

Inflammatory Response to Hydroxyurea Therapy in Sickle Cell Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00784082
• Other study ID #: P080102
• Secondary ID: 2008-005077-35
• Status: Completed
• Phase: N/A
• First received: October 27, 2008
• Last updated: January 30, 2013
• Start date: May 2009
• Est. completion date: November 2012

Study information

• Verified date: January 2013
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: November 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 3 Years and older

Eligibility

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

Study Design

N/A

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Drug:
• Hydroxycarbamide, Hydroxyurea (drug)
hydroxyurea 20-25 mg/kg/day since at least 3 months

Locations

Country	Name	City	State
France	Hopital Louis Mourier	Colombes

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of plasma inflammatory markers	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).	Day 1	No
Secondary	Clinical data	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)	Day 1	No
Secondary	Hematological at baseline	Hematological at baseline (Hb, reticulocytes, MCV, platelets, leukocytes, PN and monocytes, lymphocytes, erythroblasts, iron status)	Day 1	No
Secondary	Determination of HbF	Determination of HbF	Day 1	No
Secondary	Determination of markers of the "acute phase"	Determination of markers of the "acute phase": CRP and orosomucoid	Day 1	No
Secondary	Plasma concentrations	Plasma concentrations of HU just before taking HU (residual) and H2 after dosing.	Day 1	No