Clinical trial NCT03114137: Heart Arteries and Sickle Cell Disease / Coeur Artères DREpanocytose
Official title: Heart, Arteries and Sikle Cell Disease, a Multicentric Cohort of Cardiovascular Complications in Subsaharan Africa
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Sickle Cell Anemia
Sickle Cell Disease
Keywords: Sub-Saharan Africa
Sickle Cell Disease
Vasculopathy
Nephropathy
Pulmonary hypertension
cardiac disease
hemolysis
pulse wave velocity
blood viscosity
Lead sponsor: Cardiologie et Développement
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
name: University of Paris 5 - Rene Descartes
name: laboratory of excellence GR-Ex
First posted: 2017-04-14
Enrollment: 4500
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children and adult patients with the sickle cell disease living in subSaharan Africa

Brief summary: The CADRE study is a multinational observational cohort of patients with sickle-cell disease (SCD) in five west and central sub-Saharan African countries. The aim of this project is to describe the incidence and assess the predictive factors of SCD-related micro- and macro-vascular complications in sub-Saharan Africa.

Detailed description: Sickle cell disease (SCD), one of the lost common genetic diseases worldwide, is caused by a mutation in the β globin gene. Most patients with this disease are homozygous for the βS allele (SS), whereas others have inherited a βS allele with another mutation in the β globin gene. In addition to repeated acute ischemic insults due to the red blood cells sickling in the microcirculation, a chronic vasculopathy leads to organ injuries, such as kidney disease, stroke, pulmonary hypertension, retinopathy, bone infarcts, and leg ulcers.

CADRE is a multinational prospective observational study undertaken in five countries in sub-Saharan Africa. Patients with SCD will be recruited through outpatients' clinics in public, university and private hospitals and research centers in five countries. The CADRE protocol was approved by the relevant national ethics committee in each of the participating countries.

Primary endpoint is to measure the prevalence and the incidence of the main vascular complications in the main types of SCD: glomerulopathy, nephropathy, cardiopathy, pulmonary hypertension, retinopathy, strokes, osteonecrosis and leg ulcers.

Secondary endpoints are:

* to define the clinical and biological predictors of SCD vasculopathy in Africa
* to search for genetic risk factors for the SCD-related cardiovascular complications, in particular alpha thalassemia, persistence of foetal hemoglobin and other candidate genetic polymorphisms
* to search for functional risk factors (pulse wave velocity, capillary vasodilatation, blood visosity) for the SCD-related cardiovascular complications
* to search for new biological determinant of SCD-related cardiovascular complications, in particular alternative markers of hemolysis (microparticules, free heme) and inflammation (cytokines, leucocytes phenotyping, NET (neutrophile extracellular traps))

Eligibility criteria: Inclusion Criteria:

* age: five-year-old or more
* signature of informed consent Patients : major sickle cell syndrome confirmed by hemoglobin phenotyping: SS, SC, SBeta+ or Sbeta0 Controls : healthy parents or siblings of the patients, hospital staff or their children, matched on age+/- 3 years and country (1 control for 4 patients)

Exclusion Criteria:

unstable clinical status such as:

* vaso-occlusive crisis in the previous 15 days
* fever or infectious disease in the previous 15 days
* transfusion in the previous 2 months

Primary outcomes:
measure: Prevalence and 10 year-incidence of SCD-related vascular complications in different phenotypes of SCD: glomerulopathy
timeFrame: 10 years
measure: Prevalence and 10 year-incidence of SCD-related vascular complications in different phenotypes of SCD: cardiopathy
timeFrame: 10 years
measure: Prevalence and 10 year-incidence of SCD-related vascular complications in different phenotypes of SCD: pulmonary hypertension
timeFrame: 10 years
measure: Prevalence and incidence and the 10 year-incidence of the main SCD-related vascular complications in different phenotypes of SCD: retinopathy
timeFrame: 10 years
measure: Prevalence and 10 year-incidence of SCD-related vascular complications in different phenotypes of SCD:stroke
timeFrame: 10 years
measure: Prevalence and 10 year-incidence of SCD-related vascular complications in different phenotypes of SCD:osteonecrosis
timeFrame: 10 years
measure: Prevalence and 10 year-incidence of SCD-related vascular complications in different phenotypes of SCD: leg ulcers
timeFrame: 10 years
measure: Prevalence and 10 year-incidence of SCD-related vascular complications in different phenotypes of SCD: priapism
timeFrame: 10 years
Secondary outcomes:
measure: Potential biological risk marker measured at baseline and follow up visits: carotid-femoral pulse wave velocity
timeFrame: 10 years
measure: Potential biological risk marker measured at baseline and follow up visits: complete blood count
timeFrame: 10 years
measure: Potential biological risk marker measured at baseline and follow up visits: LDH level
timeFrame: 10 years
measure: Potential biological risk marker measured at baseline and follow up visits: bilirubin level
timeFrame: 10 years
measure: Potential biological risk marker measured at baseline and follow up visits: microparticules measure
timeFrame: 10 years
measure: Potential biological risk marker measured at baseline and follow up visits: free heme level
timeFrame: 10 years
measure: Potential biological risk marker measured at baseline and follow up visits: inflammatory cytokines
timeFrame: 10 years
measure: Potential biological risk marker measured at baseline and follow up visits: neutrophil extracellular traps
timeFrame: 10 years
Other outcomes:
Locations:
city: Yaounde
country: Cameroon
facility: Central Hospital of Yaounde
city: Yaounde
country: Cameroon
facility: Centre mère et enfant / fondation Chantal Biya
city: Yaounde
country: Cameroon
facility: Centre Pasteur du Cameroun
city: Yaounde
country: Cameroon
facility: Pediatrics unit, Centre Hospitalier d'Essos
city: Kinshasa
country: Congo, The Democratic Republic of the
facility: Centre hospitalier Monkole
city: Abidjan
country: Côte D'Ivoire
facility: Hematology Unit, CHU Yopougon
city: Abidjan
country: Côte D'Ivoire
facility: Institut de cardiologie
city: Libreville
country: Gabon
facility: CIRMF
city: Bamako
country: Mali
facility: Cardiology Unit, Centre gyneco-obstretrique
city: Bamako
country: Mali
facility: Centre de Recherche et de Lutte contre la Drepanocytose
city: Dakar
country: Senegal
facility: Centre hospitalier d'enfants Albert Royer
city: Dakar
country: Senegal
facility: Centre hospitalo-universotaire de Fann, Cardiology department
city: Dakar
country: Senegal
facility: Centre national de transfusion sanguine
Study officials:
affiliation: Cardiologie et Developpement
name: Xavier Jouven, MD PhD
role: PRINCIPAL_INVESTIGATOR
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