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Inflammatory Response to Hydroxyurea Therapy in Sickle Cell Disease

Primary Purpose

Sickle Cell Disease

Status
Completed
Phase
Locations
France
Study Type
Observational
Intervention
Hydroxycarbamide, Hydroxyurea (drug)
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an observational trial for Sickle Cell Disease focused on measuring Sickle cell disease, hydroxyurea, inflammation

Eligibility Criteria

3 Years - undefined (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Hopital Louis Mourier

Arms of the Study

Arm 1

Arm 2

Arm Type

Arm Label

Homozygous SS sickle cell children

Homozygous SS children

Arm Description

Hydroxycarbamide, Hydroxyurea (drug): 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.

Hydroxycarbamide, Hydroxyurea (drug): 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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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)
Hematological at baseline
Hematological at baseline (Hb, reticulocytes, MCV, platelets, leukocytes, PN and monocytes, lymphocytes, erythroblasts, iron status)
Determination of HbF
Determination of HbF
Determination of markers of the "acute phase"
Determination of markers of the "acute phase": CRP and orosomucoid
Plasma concentrations
Plasma concentrations of HU just before taking HU (residual) and H2 after dosing.

Full Information

First Posted
October 27, 2008
Last Updated
January 30, 2013
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT00784082
Brief Title
Inflammatory Response to Hydroxyurea Therapy in Sickle Cell Disease
Official Title
Inflammatory Response to Hydroxyurea Therapy in Sickle Cell Disease
Study Type
Observational

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
May 2009 (undefined)
Primary Completion Date
October 2012 (Actual)
Study Completion Date
November 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease
Keywords
Sickle cell disease, hydroxyurea, inflammation

7. Study Design

Enrollment
62 (Actual)
Biospecimen Retention
Samples With DNA
Biospecimen Description
Sample with DNA

8. Arms, Groups, and Interventions

Arm Title
Homozygous SS sickle cell children
Arm Description
Hydroxycarbamide, Hydroxyurea (drug): 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.
Arm Title
Homozygous SS children
Arm Description
Hydroxycarbamide, Hydroxyurea (drug): 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.
Intervention Type
Drug
Intervention Name(s)
Hydroxycarbamide, Hydroxyurea (drug)
Intervention Description
hydroxyurea 20-25 mg/kg/day since at least 3 months
Primary Outcome Measure Information:
Title
Determination of plasma inflammatory markers
Description
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).
Time Frame
Day 1
Secondary Outcome Measure Information:
Title
Clinical data
Description
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)
Time Frame
Day 1
Title
Hematological at baseline
Description
Hematological at baseline (Hb, reticulocytes, MCV, platelets, leukocytes, PN and monocytes, lymphocytes, erythroblasts, iron status)
Time Frame
Day 1
Title
Determination of HbF
Description
Determination of HbF
Time Frame
Day 1
Title
Determination of markers of the "acute phase"
Description
Determination of markers of the "acute phase": CRP and orosomucoid
Time Frame
Day 1
Title
Plasma concentrations
Description
Plasma concentrations of HU just before taking HU (residual) and H2 after dosing.
Time Frame
Day 1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Study Population Description
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
Sampling Method
Non-Probability Sample
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marie-Hélène Odièvre, MD, PhD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hopital Louis Mourier
City
Colombes
ZIP/Postal Code
92701
Country
France

12. IPD Sharing Statement

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Inflammatory Response to Hydroxyurea Therapy in Sickle Cell Disease

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