Sickle Cell DiseaseNCT00784082
Inflammatory Response to Hydroxyurea Therapy in Sickle Cell Disease
An observational study of Sickle Cell Disease, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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. Read more about this study
- Who is it for?
- Ages 3 years and olderHealthy volunteers can take part
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Hydroxycarbamide, Hydroxyurea (drug)
- How many people
- 62 participants
- Where
- 1 siteFrance
- Study dates
- May 2009to Nov 2012
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
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
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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).
- Conditions
- Sickle Cell Disease
- Being tested
- Hydroxycarbamide, Hydroxyurea (drug)
- Keywords
- Sickle cell disease, hydroxyurea, inflammation
- Medical subject headings
- Anemia, Sickle Cell, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydroxycarbamide, Hydroxyurea (drug)Drug
hydroxyurea 20-25 mg/kg/day since at least 3 months
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Hydroxycarbamide, Hydroxyurea (drug) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Day 1
Secondary outcomes (5)
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)
Measured: Day 1
Hematological at baseline
Hematological at baseline (Hb, reticulocytes, MCV, platelets, leukocytes, PN and monocytes, lymphocytes, erythroblasts, iron status)
Measured: Day 1
Determination of HbF
Determination of HbF
Measured: Day 1
Determination of markers of the "acute phase"
Determination of markers of the "acute phase": CRP and orosomucoid
Measured: Day 1
Plasma concentrations
Plasma concentrations of HU just before taking HU (residual) and H2 after dosing.
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2008 (estimated)
- Study startMay 2009
- Primary completionOct 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marie-Hélène Odièvre, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00784082
- Sponsor's protocol ID
- P080102
- Other IDs
- 2008-005077-35, 2008
- Status last verified
- Jan 2013
- First submitted
- 27 Oct 2008
- Last updated
- 31 Jan 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inflammatory Response to Hydroxyurea Therapy in Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT00784082
- Acronym / sponsor ID
- P080102
- Conditions
- Sickle Cell Disease
- Keywords
- Sickle cell disease, hydroxyurea, inflammation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- May 2009
- Primary completion
- Oct 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 3 Nov 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Homozygous SS sickle cell children | – | Drug: Hydroxycarbamide, Hydroxyurea (drug)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. |
| Homozygous SS children | – | Drug: Hydroxycarbamide, Hydroxyurea (drug)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. |
Who may qualify
- Ages
- 3 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- 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
Key inclusion criteria (6 listed)
- 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 :
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hydroxycarbamide, Hydroxyurea (drug)hydroxyurea 20-25 mg/kg/day since at least 3 months | Drug | Homozygous SS children, Homozygous SS sickle cell children |
Primary outcome
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).
5 secondary outcomes
Clinical data
Time frame: Day 1
Hematological at baseline
Time frame: Day 1
Determination of HbF
Time frame: Day 1
Determination of markers of the "acute phase"
Time frame: Day 1
Plasma concentrations
Time frame: Day 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marie-Hélène Odièvre, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sickle Cell Disease, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determination of plasma inflammatory markers (time frame: Day 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2013.