Heart Arteries and Sickle Cell Disease / Coeur Artères DREpanocytose

NCT03114137 | Unknown

• 1 other identifier: 002
• Study Type: observational
• Target: 4,500
• Locations: 6 countries
• Sites: 13

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.

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

Outcome Measures

Primary Outcomes (8)

• Prevalence and 10 year-incidence of SCD-related vascular complications in different phenotypes of SCD: glomerulopathy

  urinary albumin/creatinin ratio (mg/g)

  10 years

• Prevalence and 10 year-incidence of SCD-related vascular complications in different phenotypes of SCD: cardiopathy

  left ventricular ejection fraction \< 60 %

  10 years

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

  tricuspid regurgitation jet velocity (m/s)

  10 years

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

  retinal examination

  10 years

• Prevalence and 10 year-incidence of SCD-related vascular complications in different phenotypes of SCD:stroke

  clinical diagnosis

  10 years

• Prevalence and 10 year-incidence of SCD-related vascular complications in different phenotypes of SCD:osteonecrosis

  standard radiography

  10 years

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

  clinical diagnosis

  10 years

• Prevalence and 10 year-incidence of SCD-related vascular complications in different phenotypes of SCD: priapism

  clinical diagnosis

  10 years

Secondary Outcomes (8)

• Potential biological risk marker measured at baseline and follow up visits: carotid-femoral pulse wave velocity

  10 years

• Potential biological risk marker measured at baseline and follow up visits: complete blood count

  10 years

• Potential biological risk marker measured at baseline and follow up visits: LDH level

  10 years

• Potential biological risk marker measured at baseline and follow up visits: bilirubin level

  10 years

• Potential biological risk marker measured at baseline and follow up visits: microparticules measure

  10 years

Study Arms (2)

sickle cell patients

* age: five-year-old or more * major sickle cell syndrome confirmed by hemoglobin phenotype: SS, SC, SBeta+ or Sbeta0 * steady state defined as the absence of vaso-occlusive crisis for the previous 15 days, absence of fever or infectious disease for the previous 8 days and absence of transfusion for the previous 2 months

control patients

* volunteer parents or siblings of sickle cell patients * hospital staff or their children matched on country and age +/- 3 ans with the patients

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Children and adult patients with the sickle cell disease living in subSaharan Africa

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Cardiologie et Développement: lead
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator
• University of Paris 5 - Rene Descartes: collaborator
• laboratory of excellence GR-Ex: collaborator

Study Sites (13)

Central Hospital of Yaounde

Yaoundé, Cameroon

RECRUITING

Centre mère et enfant / fondation Chantal Biya

Yaoundé, Cameroon

RECRUITING

Centre Pasteur du Cameroun

Yaoundé, Cameroon

RECRUITING

Pediatrics unit, Centre Hospitalier d'Essos

Yaoundé, Cameroon

RECRUITING

Hematology Unit, CHU Yopougon

Abidjan, Côte d’Ivoire

RECRUITING

Institut de cardiologie

Abidjan, Côte d’Ivoire

ACTIVE NOT RECRUITING

Centre hospitalier Monkole

Kinshasa, Democratic Republic of the Congo

RECRUITING

CIRMF

Libreville, Gabon

COMPLETED

Cardiology Unit, Centre gyneco-obstretrique

Bamako, Mali

ACTIVE NOT RECRUITING

Centre de Recherche et de Lutte contre la Drepanocytose

Bamako, Mali

RECRUITING

Centre hospitalier d'enfants Albert Royer

Dakar, Senegal

RECRUITING

Centre hospitalo-universotaire de Fann, Cardiology department

Dakar, Senegal

RECRUITING

Centre national de transfusion sanguine

Dakar, Senegal

RECRUITING

Related Publications (16)

• Kato GJ, Gladwin MT, Steinberg MH. Deconstructing sickle cell disease: reappraisal of the role of hemolysis in the development of clinical subphenotypes. Blood Rev. 2007 Jan;21(1):37-47. doi: 10.1016/j.blre.2006.07.001. Epub 2006 Nov 7.

  PMID: 17084951 BACKGROUND

• Hebbel RP. Reconstructing sickle cell disease: a data-based analysis of the "hyperhemolysis paradigm" for pulmonary hypertension from the perspective of evidence-based medicine. Am J Hematol. 2011 Feb;86(2):123-54. doi: 10.1002/ajh.21952.

  PMID: 21264896 BACKGROUND

• Nouraie M, Lee JS, Zhang Y, Kanias T, Zhao X, Xiong Z, Oriss TB, Zeng Q, Kato GJ, Gibbs JS, Hildesheim ME, Sachdev V, Barst RJ, Machado RF, Hassell KL, Little JA, Schraufnagel DE, Krishnamurti L, Novelli E, Girgis RE, Morris CR, Rosenzweig EB, Badesch DB, Lanzkron S, Castro OL, Goldsmith JC, Gordeuk VR, Gladwin MT; Walk-PHASST Investigators and Patients. The relationship between the severity of hemolysis, clinical manifestations and risk of death in 415 patients with sickle cell anemia in the US and Europe. Haematologica. 2013 Mar;98(3):464-72. doi: 10.3324/haematol.2012.068965. Epub 2012 Sep 14.

  PMID: 22983573 BACKGROUND

• Gordeuk VR, Minniti CP, Nouraie M, Campbell AD, Rana SR, Luchtman-Jones L, Sable C, Dham N, Ensing G, Prchal JT, Kato GJ, Gladwin MT, Castro OL. Elevated tricuspid regurgitation velocity and decline in exercise capacity over 22 months of follow up in children and adolescents with sickle cell anemia. Haematologica. 2011 Jan;96(1):33-40. doi: 10.3324/haematol.2010.030767. Epub 2010 Sep 30.

  PMID: 20884713 BACKGROUND

• Maier-Redelsperger M, Levy P, Lionnet F, Stankovic K, Haymann JP, Lefevre G, Avellino V, Perol JP, Girot R, Elion J. Strong association between a new marker of hemolysis and glomerulopathy in sickle cell anemia. Blood Cells Mol Dis. 2010 Dec 15;45(4):289-92. doi: 10.1016/j.bcmd.2010.08.001. Epub 2010 Sep 15.

  PMID: 20833087 BACKGROUND

• Taylor JG 6th, Nolan VG, Mendelsohn L, Kato GJ, Gladwin MT, Steinberg MH. Chronic hyper-hemolysis in sickle cell anemia: association of vascular complications and mortality with less frequent vasoocclusive pain. PLoS One. 2008 May 7;3(5):e2095. doi: 10.1371/journal.pone.0002095.

  PMID: 18461136 BACKGROUND

• Gladwin MT, Sachdev V, Jison ML, Shizukuda Y, Plehn JF, Minter K, Brown B, Coles WA, Nichols JS, Ernst I, Hunter LA, Blackwelder WC, Schechter AN, Rodgers GP, Castro O, Ognibene FP. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med. 2004 Feb 26;350(9):886-95. doi: 10.1056/NEJMoa035477.

  PMID: 14985486 BACKGROUND

• Kato GJ, McGowan V, Machado RF, Little JA, Taylor J 6th, Morris CR, Nichols JS, Wang X, Poljakovic M, Morris SM Jr, Gladwin MT. Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease. Blood. 2006 Mar 15;107(6):2279-85. doi: 10.1182/blood-2005-06-2373. Epub 2005 Nov 15.

  PMID: 16291595 BACKGROUND

• Connes P, Lamarre Y, Hardy-Dessources MD, Lemonne N, Waltz X, Mougenel D, Mukisi-Mukaza M, Lalanne-Mistrih ML, Tarer V, Tressieres B, Etienne-Julan M, Romana M. Decreased hematocrit-to-viscosity ratio and increased lactate dehydrogenase level in patients with sickle cell anemia and recurrent leg ulcers. PLoS One. 2013 Nov 4;8(11):e79680. doi: 10.1371/journal.pone.0079680. eCollection 2013.

  PMID: 24223994 BACKGROUND

• Nolan VG, Wyszynski DF, Farrer LA, Steinberg MH. Hemolysis-associated priapism in sickle cell disease. Blood. 2005 Nov 1;106(9):3264-7. doi: 10.1182/blood-2005-04-1594. Epub 2005 Jun 28.

  PMID: 15985542 BACKGROUND

• Kato GJ, Hsieh M, Machado R, Taylor J 6th, Little J, Butman JA, Lehky T, Tisdale J, Gladwin MT. Cerebrovascular disease associated with sickle cell pulmonary hypertension. Am J Hematol. 2006 Jul;81(7):503-10. doi: 10.1002/ajh.20642.

  PMID: 16755569 BACKGROUND

• Steinberg MH, Sebastiani P. Genetic modifiers of sickle cell disease. Am J Hematol. 2012 Aug;87(8):795-803. doi: 10.1002/ajh.23232. Epub 2012 May 28.

  PMID: 22641398 BACKGROUND

• Ranque B, Menet A, Boutouyrie P, Diop IB, Kingue S, Diarra M, N'Guetta R, Diallo D, Diop S, Diagne I, Sanogo I, Tolo A, Chelo D, Wamba G, Gonzalez JP, Abough'elie C, Diakite CO, Traore Y, Legueun G, Deme-Ly I, Faye BF, Seck M, Kouakou B, Kamara I, Le Jeune S, Jouven X. Arterial Stiffness Impairment in Sickle Cell Disease Associated With Chronic Vascular Complications: The Multinational African CADRE Study. Circulation. 2016 Sep 27;134(13):923-33. doi: 10.1161/CIRCULATIONAHA.115.021015. Epub 2016 Aug 31.

  PMID: 27582423 RESULT

• Ranque B, Menet A, Diop IB, Thiam MM, Diallo D, Diop S, Diagne I, Sanogo I, Kingue S, Chelo D, Wamba G, Diarra M, Anzouan JB, N'Guetta R, Diakite CO, Traore Y, Legueun G, Deme-Ly I, Belinga S, Boidy K, Kamara I, Tharaux PL, Jouven X. Early renal damage in patients with sickle cell disease in sub-Saharan Africa: a multinational, prospective, cross-sectional study. Lancet Haematol. 2014 Nov;1(2):e64-73. doi: 10.1016/S2352-3026(14)00007-6. Epub 2014 Oct 28.

  PMID: 27030156 RESULT

• Ranque B, Diaw M, Dembele AK, Lapoumeroulie C, Offredo L, Tessougue O, Gueye SM, Diallo D, Diop S, Colin-Aronovicz Y, Jouven X, Blanc-Brude O, Tharaux PL, Le Jeune S, Connes P, Romana M, Le Van Kim C. Association of haemolysis markers, blood viscosity and microcirculation function with organ damage in sickle cell disease in sub-Saharan Africa (the BIOCADRE study). Br J Haematol. 2023 Oct;203(2):319-326. doi: 10.1111/bjh.19006. Epub 2023 Aug 15.

  PMID: 37583261 DERIVED

• Dembele AK, Lapoumeroulie C, Diaw M, Tessougue O, Offredo L, Diallo DA, Diop S, Elion J, Colin-Aronovicz Y, Tharaux PL, Jouven X, Romana M, Ranque B, Le Van Kim C. Cell-derived microparticles and sickle cell disease chronic vasculopathy in sub-Saharan Africa: A multinational study. Br J Haematol. 2021 Feb;192(3):634-642. doi: 10.1111/bjh.17242. Epub 2020 Nov 29.

  PMID: 33249569 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

whole blood plasma saliva urines

MeSH Terms

Conditions

Anemia, Sickle Cell; Vascular Diseases; Kidney Diseases; Hypertension, Pulmonary; Heart Diseases; Hemolysis

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; Cardiovascular Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lung Diseases; Respiratory Tract Diseases; Hypertension; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Xavier Jouven, MD PhD

  Cardiologie et Developpement

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Brigitte Ranque, MD PhD

CONTACT

brigitte.ranque@aphp.fr

Louise Boyer-Chatenet, MS

CONTACT

+33156093656; louise.boyer-chatenet-ext@aphp.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 10 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 30, 2017
• First Posted: April 14, 2017
• Study Start: March 1, 2012
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2022
• Last Updated: May 25, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); GA (1); CA (4); CÔ (2); MA (2); SE (3)