Substudy of CADRE: for People With Extreme Phenotype: BIOCADRE
NCT ID: NCT03352986
Last Updated: 2017-11-24
Study Results
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Basic Information
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UNKNOWN
300 participants
OBSERVATIONAL
2017-05-15
2019-12-31
Brief Summary
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Detailed Description
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The project aims at better understanding SCD chronic vascular complications and in particular to explore extensively the different mechanisms associated with hemolysis. This will be addressed through both an epidemiological approach and a hypotheses-driven pathophysiological approach. On the one hand, a descriptive and analytic epidemiological study will isolate clusters of clinical, functional and usual biological phenotypes in SCD patients and look for new mechanistic and biological markers predictive of chronic vascular complications in SCD with SS phenotype. Investigators will specifically investigate i) microcirculation functions using peripheral arterial tonometry, ii) blood and plasma viscosities, iii) level of plasma blood cell derived microparticles, free hemoglobin, and the free heme content of erythrocytes-derived microparticles and expression of Duffy erythrocyte antigen, the unique erythroid receptor for chemokines. One the other hand, investigators will test novel markers and modifiers of hemolysis and heme metabolism and assess their relationship with inflammation and vascular phenotypes.These different biomarkers will be compared between the selected subgroups of patients with extreme vascular phenotype.
Methods: The project involves a transversal case control study, nested in the CADRE cohort, recently built up by Partner 1 and African collaborators. CADRE is the largest ongoing epidemiological cohort, including 4,300 SCD patients and 1,000 controls in five west and central African countries, in which various chronic complications of SCD have already been registered. The present second phase study will be conducted in the centres of Dakar and Bamako. Patients' selection will be performed in the existing database to obtain 6 subgroups of 40 SS patients with one of the main vascular chronic complications or none of them, for a total of 240 patients. Selected patients will be recalled during one year in parallel in the 2 recruiting centres. Clinical phenotyping, usual biology, functional microvascular functions (peripheral arterial tonometry), and blood/plasma viscosities analyses will be performed in the African recruiting centres after training of technicians, PhD and MD students by the French partners. Plasma samples, microparticles and extracellular DNA, will be prepared and frozen for further analyses in the partner's laboratories. DNA will be collected for each subject. A principal component analysis will isolate clusters of clinical complications, functional and biological markers and a multivariate logistic regression will quantify the effect of these markers on the risk of vasculopathy, with adjustment on all known SCD modifying factors.
Expected results: 1) The identification of high risk SCD patients for chronic vascular complications using new biomarkers, 2) A better understanding of chronic vascular disease process at the mechanistic and biological (viscosity, hemolysis, erythrocyte derived microparticles, inflammatory cytokines and receptors) levels, 3) The identification of endophenotypes and constitution of DNA bank for further genetic studies.
Conditions
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Keywords
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Study Design
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COHORT
PROSPECTIVE
Study Groups
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osteonecrosis
Sickle cell patients with osteonecrosis as a vascular main complication
biological analysis
biological analysis will be performed in the 6 groups of patients
peripheral arterial tonometry
peripheral arterial tonometry will be performed in the 6 groups of patients
leg ulcer
Sickle cell patients with leg ulcer as a vascular main complication
biological analysis
biological analysis will be performed in the 6 groups of patients
peripheral arterial tonometry
peripheral arterial tonometry will be performed in the 6 groups of patients
microalbuminuria
Sickle cell patients with microalbuminuria as a vascular main complication
biological analysis
biological analysis will be performed in the 6 groups of patients
peripheral arterial tonometry
peripheral arterial tonometry will be performed in the 6 groups of patients
pulmonary hypertension
Sickle cell patients with pulmonary hypertension as a vascular main complication
biological analysis
biological analysis will be performed in the 6 groups of patients
peripheral arterial tonometry
peripheral arterial tonometry will be performed in the 6 groups of patients
stroke
Sickle cell patients with strocke as a vascular main complication
biological analysis
biological analysis will be performed in the 6 groups of patients
peripheral arterial tonometry
peripheral arterial tonometry will be performed in the 6 groups of patients
priapism
Sickle cell patients with priapism as a vascular main complication
biological analysis
biological analysis will be performed in the 6 groups of patients
peripheral arterial tonometry
peripheral arterial tonometry will be performed in the 6 groups of patients
Interventions
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biological analysis
biological analysis will be performed in the 6 groups of patients
peripheral arterial tonometry
peripheral arterial tonometry will be performed in the 6 groups of patients
Eligibility Criteria
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Inclusion Criteria
Exclusion Criteria
* vaso-occlusive crisis in the previous 15 days
* infection in the previous 8 days
10 Years
ALL
No
Sponsors
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Institut National de la Santé Et de la Recherche Médicale, France
OTHER_GOV
Cardiologie et Développement
OTHER
Responsible Party
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Principal Investigators
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Brigitte Ranque, MD
Role: PRINCIPAL_INVESTIGATOR
Institut National de la Santé Et de la Recherche Médicale, France
Locations
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Centre de Recherches er de Lutte contre la Drépanocytose
Bamako, , Mali
Centre National de Transfusion Sanguine
Dakar, , Senegal
Countries
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Central Contacts
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Facility Contacts
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Dapa Diallo, MD
Role: primary
Saliou Diop, MD
Role: primary
References
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Other Identifiers
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003
Identifier Type: -
Identifier Source: org_study_id