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Heart Arteries and Sickle Cell Disease / Coeur Artères DREpanocytose

Conditions
Sickle Cell Anemia
Sickle Cell Disease
Registration Number
NCT03114137
Lead Sponsor
Cardiologie et Développement
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))

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
4500
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

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Prevalence and 10 year-incidence of SCD-related vascular complications in different phenotypes of SCD: cardiopathy10 years

left ventricular ejection fraction \< 60 %

Prevalence and incidence and the 10 year-incidence of the main SCD-related vascular complications in different phenotypes of SCD: retinopathy10 years

retinal examination

Prevalence and 10 year-incidence of SCD-related vascular complications in different phenotypes of SCD: leg ulcers10 years

clinical diagnosis

Prevalence and 10 year-incidence of SCD-related vascular complications in different phenotypes of SCD:osteonecrosis10 years

standard radiography

Prevalence and 10 year-incidence of SCD-related vascular complications in different phenotypes of SCD:stroke10 years

clinical diagnosis

Prevalence and 10 year-incidence of SCD-related vascular complications in different phenotypes of SCD: glomerulopathy10 years

urinary albumin/creatinin ratio (mg/g)

Prevalence and 10 year-incidence of SCD-related vascular complications in different phenotypes of SCD: pulmonary hypertension10 years

tricuspid regurgitation jet velocity (m/s)

Prevalence and 10 year-incidence of SCD-related vascular complications in different phenotypes of SCD: priapism10 years

clinical diagnosis

Secondary Outcome Measures
NameTimeMethod
Potential biological risk marker measured at baseline and follow up visits: inflammatory cytokines10 years
Potential biological risk marker measured at baseline and follow up visits: complete blood count10 years
Potential biological risk marker measured at baseline and follow up visits: neutrophil extracellular traps10 years
Potential biological risk marker measured at baseline and follow up visits: carotid-femoral pulse wave velocity10 years

measured by Pulsepen, m/s)

Potential biological risk marker measured at baseline and follow up visits: LDH level10 years
Potential biological risk marker measured at baseline and follow up visits: bilirubin level10 years
Potential biological risk marker measured at baseline and follow up visits: microparticules measure10 years
Potential biological risk marker measured at baseline and follow up visits: free heme level10 years

Trial Locations

Locations (13)

Centre de Recherche et de Lutte contre la Drepanocytose

🇲🇱

Bamako, Mali

Hematology Unit, CHU Yopougon

🇨🇮

Abidjan, Côte D'Ivoire

Centre mère et enfant / fondation Chantal Biya

🇨🇲

Yaounde, Cameroon

CIRMF

🇬🇦

Libreville, Gabon

Cardiology Unit, Centre gyneco-obstretrique

🇲🇱

Bamako, Mali

Centre national de transfusion sanguine

🇸🇳

Dakar, Senegal

Pediatrics unit, Centre Hospitalier d'Essos

🇨🇲

Yaounde, Cameroon

Central Hospital of Yaounde

🇨🇲

Yaounde, Cameroon

Centre Pasteur du Cameroun

🇨🇲

Yaounde, Cameroon

Centre hospitalier Monkole

🇨🇩

Kinshasa, Congo, The Democratic Republic of the

Institut de cardiologie

🇨🇮

Abidjan, Côte D'Ivoire

Centre hospitalier d'enfants Albert Royer

🇸🇳

Dakar, Senegal

Centre hospitalo-universotaire de Fann, Cardiology department

🇸🇳

Dakar, Senegal

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