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Inflammatory Response to Hydroxyurea Therapy in Sickle Cell Disease

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ClinicalTrials.gov Identifier: NCT00784082
Recruitment Status : Completed
First Posted : November 3, 2008
Last Update Posted : January 31, 2013
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Tracking Information
First Submitted Date October 27, 2008
First Posted Date November 3, 2008
Last Update Posted Date January 31, 2013
Study Start Date May 2009
Actual Primary Completion Date October 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: January 30, 2013)
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).
Original Primary Outcome Measures Not Provided
Change History Complete list of historical versions of study NCT00784082 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: January 30, 2013)
  • 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)
  • Hematological at baseline [ Time Frame: Day 1 ]
    Hematological at baseline (Hb, reticulocytes, MCV, platelets, leukocytes, PN and monocytes, lymphocytes, erythroblasts, iron status)
  • Determination of HbF [ Time Frame: Day 1 ]
    Determination of HbF
  • Determination of markers of the "acute phase" [ Time Frame: Day 1 ]
    Determination of markers of the "acute phase": CRP and orosomucoid
  • Plasma concentrations [ Time Frame: Day 1 ]
    Plasma concentrations of HU just before taking HU (residual) and H2 after dosing.
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Inflammatory Response to Hydroxyurea Therapy in Sickle Cell Disease
Official Title Inflammatory Response to Hydroxyurea Therapy in Sickle Cell Disease
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 Type Observational
Study Design Not Provided
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Sample with DNA
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
Condition Sickle Cell Disease
Intervention Drug: Hydroxycarbamide, Hydroxyurea (drug)
hydroxyurea 20-25 mg/kg/day since at least 3 months
Study Groups/Cohorts
  • Homozygous SS sickle cell children

    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.
    Intervention: Drug: Hydroxycarbamide, Hydroxyurea (drug)
  • Homozygous SS children

    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.
    Intervention: Drug: Hydroxycarbamide, Hydroxyurea (drug)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: January 30, 2013)
62
Original Estimated Enrollment
 (submitted: October 31, 2008)
100
Actual Study Completion Date November 2012
Actual Primary Completion Date October 2012   (Final data collection date for primary outcome measure)
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
Sex/Gender
Sexes Eligible for Study: All
Ages 3 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries France
Removed Location Countries  
 
Administrative Information
NCT Number NCT00784082
Other Study ID Numbers P080102
2008-005077-35 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Assistance Publique - Hôpitaux de Paris
Study Sponsor Assistance Publique - Hôpitaux de Paris
Collaborators Not Provided
Investigators
Principal Investigator: Marie-Hélène Odièvre, MD, PhD Assistance Publique - Hôpitaux de Paris
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date January 2013