Skip to main content
OpenTrials
Completed

NCT Number: NCT00784082

Inflammatory Response to Hydroxyurea Therapy in Sickle Cell Disease

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Sickle Cell Disease Anemia Anemia, Hemolytic Anemia, Hemolytic, Congenital Anemia, Sickle Cell Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinopathies Inflammation Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

3 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Hopital Louis Mourier

Colombes, 92701, France

About this study

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).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Hydroxycarbamide, Hydroxyurea (drug)

Drug

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

Primary outcomes

  1. 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

  1. Clinical data

    Time frame: 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)

  2. Hematological at baseline

    Time frame: Day 1

    Hematological at baseline (Hb, reticulocytes, MCV, platelets, leukocytes, PN and monocytes, lymphocytes, erythroblasts, iron status)

  3. Determination of HbF

    Time frame: Day 1

    Determination of HbF

  4. Determination of markers of the "acute phase"

    Time frame: Day 1

    Determination of markers of the "acute phase": CRP and orosomucoid

  5. Plasma concentrations

    Time frame: Day 1

    Plasma concentrations of HU just before taking HU (residual) and H2 after dosing.

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Important dates

Study start
2009
Primary completion
2012
Study completion
2012
First posted
Nov 3, 2008
Registry last updated
Jan 31, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.