Sickle Cell Disease and Endothelial Progenitor Cells (EPCs)

NCT00783627 | Completed

• 1 other identifier: P 050310
• Study Type: observational
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

Sickle Cell Disease (SCD) is the most prevalent genetic disease of haemoglobin.The underlying abnormality in the red blood cell (RBC) of SCD is the presence of abnormal sickle cell hemoglobin (HbS), which, when deoxygenated, becomes relatively insoluble, forms aggregates with other hemoglobin molecules within the RBC and causes rigid deformation of the cell. Acute pain vaso-occlusive crisis, strokes and acute chest syndrome are the main acute complications, sometimes life-threatening, often leading to organic and functional squeal. Although the common SS form of SCD is a unique gene disorder, the range of the clinical severity is remarkably wide and striking, suggesting that clinical polymorphism is due to modifier genes and environmental factors.Most of the research efforts have been focused on the biology of haemoglobin and of the red cells. Meanwhile, the complex pathophysiology of SCD is undoubtedly influenced by the many physiologic functions of the vascular wall. In line with this hypothesis are several reports of increased circulating levels of endothelium-derived surface molecules in SCD patients suggesting marked endothelial stress in SCD. Similarly, other processes that involve the endothelium, such as leukocyte adhesion and activation, may play a role in vascular occlusion. This accumulation of data raises the unanswered question of the mechanisms of endothelium maintenance and regeneration in SCD. Through these mechanisms, it is likely that function or dysfunction of the vascular endothelium contributes to the overall vascular pathobiology of this disease, which includes recurrent vaso-occlusions, stroke, leg ulcers, chronic organ ischemic damages, and neovascularizing retinopathy that affect nearly one-half (48%) of the surviving patients by the fifth decade.Thus, our groups have combined their respective clinical and biological expertises to test the hypothesis that SCD is a condition of specific endothelial stress and dysfunction upon chronic and Paracystic abnormal interactions with circulating cells and abnormal oxygen delivery to tissues. Specifically, we hypothesize that chronic endothelial stress with detachment of activated endothelial cells require increases mobilisation of the Endothelial Progenitor Cells (EPCs) that maintain endothelial homeostasis to avoid major thromboembolic events and vasospasm. Inappropriate mobilisation or maturation of the EPCs in SCD may participate to the severity of the disease.

Conditions

Sickle Cell Anemia

Keywords

Endothelium; progenitors; stem cells; sickle cell

Outcome Measures

Primary Outcomes (1)

• Measure the relative levels of endothelial progenitors (EPCs) derived from cultured mononuclear cells in patients and carefully matched healthy subjects at day 0 and after 6 months later (number of endothelial cells colony forming units).

  at day 0 and 6 months

Secondary Outcomes (2)

• Comparison of the number of circulating EPCs and CECs by FACS. The blood mononuclear cell fraction are depleted from all the haematopoietic cells using a depletion magnetic bead column. The lineage minus population is then subjected to a triple labelling

  at day 1 and at 6 months

• Correlations tests will be performed between these markers and markers of clinical severity (retinopathy, leg ulcers, number of vaso-occlusive events in the past year, microalbuminuria, leukocyte count, HbF level).

  at day 1 and 6 months

Study Arms (2)

1

Patient with sickle cell disease

Procedure: Angiography

2

Healthy volunteers

Interventions

Angiography PROCEDURE

Angiography done at the J1 visit

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Sickle cell patient : followed by the participating center. Healthy volunteers : matched on sex, age and BMI with the patients.

You may qualify if:

• Age between 18 and 45 yo
• SS genotype if patient
• Absence of relative with sickle cell anemia if healthy volunteer.
• Affiliated to the national health insurance benefit
• Signature of Informed consent form
• oral contraceptive regiment with micro or mini estro-progestative (women)

You may not qualify if:

• present or past (or interrupted for less than 3 months) therapy with hydroxyurea
• Present or recent blood transfusion and/or exchange (in the past 3 months)
• SC genotype (patients)- BMI \> 30 kg/m2
• Positive serodiagnosis for HIV, HVB, HVC
• Know allergy to fluorescein (patients)
• Hemoglobin \< 7.5 g/dL
• Pregnancy confirmed by Beta-HCG test in plasma
• Menopause
• Extreme difficulty for adequate venous puncture
• Smoking for the last month.
• ALAT or ASAT \> 2 x N
• Hypercholesterolemia (cholesterol total \> 2.,2g/L or 6.55 mmol/L),
• Treatment by statin
• Diabetes (fasting blood glucose level equal or superior to 6,1 mmol/L)
• Hypertension (systolic blood pressure \> 140 mmHg or diastolic blood pressure \> 90 mmHg).

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hopital Tenon, Assistance Publique Hôpitaux de Paris

Paris, 75020, France

Location

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Cerebral Angiography

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Neuroradiography; Neuroimaging; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Angiography; Radiography; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques, Neurological; Investigative Techniques

Study Officials

• Pierre Louis THARAUX, MDPH

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 15, 2008
• First Posted: November 3, 2008
• Study Start: November 1, 2006
• Primary Completion: June 1, 2009
• Study Completion: November 1, 2009
• Last Updated: February 23, 2011

Record last verified: 2011-02

Locations

FR (1)