Inflammatory Response to Hydroxyurea Therapy in Sickle Cell Disease - Full Text View

Sponsored by:	Assistance Publique - Hôpitaux de Paris
Information provided by:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT00784082

Purpose

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.

Condition	Intervention
Sickle Cell Disease	Drug: Hydroxycarbamide, Hydroxyurea (drug)

Genetics Home Reference related topics: sickle cell disease

MedlinePlus related topics: Sickle Cell Anemia

Drug Information available for: Hydroxyurea

U.S. FDA Resources

Study Type:	Observational
Official Title:	Inflammatory Response to Hydroxyurea Therapy in Sickle Cell Disease

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Biospecimen Retention: Samples With DNA

Biospecimen Description:

Sample with DNA

Estimated Enrollment:	100
Study Start Date:	December 2008
Estimated Study Completion Date:	June 2010
Estimated Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
0 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 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.
2 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 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.	Drug: Hydroxycarbamide, Hydroxyurea (drug) hydroxyurea 20-25 mg/kg/day since at least 3 months

Groups/Cohorts

Assigned Interventions

0

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
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.

2

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
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.

Drug: Hydroxycarbamide, Hydroxyurea (drug)

hydroxyurea 20-25 mg/kg/day since at least 3 months

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

Ages Eligible for Study:	3 Years and older
Genders Eligible for Study:	Both
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

Criteria

INCLUSION CRITERIA:

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
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00784082

Contacts

Contact: Marie-Hélène Odièvre, MD, PhD

(33) 1 40 03 19 24

marie-helene.odievre@inserm.fr

Locations

France
Hopital Louis Mourier
COLOMBES, France, 92701

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

Principal Investigator:

Marie-Hélène Odièvre, MD, PhD

Assistance Publique - Hôpitaux de Paris

More Information

Responsible Party:	department clinical research of developpement ( Yannick Vacher )
Study ID Numbers:	P080102, N° EudratCT 2008-005077-35
Study First Received:	October 27, 2008
Last Updated:	October 31, 2008
ClinicalTrials.gov Identifier:	NCT00784082
Health Authority:	France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:

Sickle cell disease, hydroxyurea, inflammation

Study placed in the following topic categories:

Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn
Hydroxyurea
Hematologic Diseases
Hemoglobinopathies
Anemia

Anemia, Hemolytic
Hemoglobinopathy
Anemia, Sickle Cell
Sickle cell anemia
Inflammation

Additional relevant MeSH terms:

Antisickling Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses

Hematologic Agents
Enzyme Inhibitors
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009