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Status unknownNCT03114137CADREUpdated May 25, 2018

Heart Arteries and Sickle Cell Disease / Coeur Artères DREpanocytose

An observational study in Sickle Cell Anemia and Sickle Cell Disease, sponsored by Cardiologie et Développement. Status unknown at 13 sites in 6 countries. Open to participants aged 5 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-05-25.

Sponsored by Cardiologie et Développement · Observational

The sponsor has not verified this record recently (last verified May 2018), so the status shown — last known as Recruiting — may be out of date.
Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
4,500
Ages
5 Years and older
Sex
All
01

Study 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.

Read the 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))
02

Conditions studied

  • Sickle Cell Anemia
  • Sickle Cell Disease

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Keywords

  • Sub-Saharan Africa
  • Sickle Cell Disease
  • Vasculopathy
  • Nephropathy
  • Pulmonary hypertension
  • cardiac disease
  • hemolysis
  • pulse wave velocity
  • blood viscosity
03

Who can participate

Ages eligible
5 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Non-probability sample

Study population

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

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

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
04

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
4,500 participants (estimated)
Target follow-up
10 Years
Patient registry
Yes
Biospecimen retention
Samples with dna

Groups and cohorts

  • 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

05

What researchers measure

Primary outcomes

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

    urinary albumin/creatinin ratio (mg/g)

    Time frame: 10 years

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

    left ventricular ejection fraction \< 60 %

    Time frame: 10 years

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

    tricuspid regurgitation jet velocity (m/s)

    Time frame: 10 years

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

    retinal examination

    Time frame: 10 years

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

    clinical diagnosis

    Time frame: 10 years

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

    standard radiography

    Time frame: 10 years

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

    clinical diagnosis

    Time frame: 10 years

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

    clinical diagnosis

    Time frame: 10 years

Secondary outcomes

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

    measured by Pulsepen, m/s)

    Time frame: 10 years

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

    Time frame: 10 years

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

    Time frame: 10 years

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

    Time frame: 10 years

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

    Time frame: 10 years

  6. Potential biological risk marker measured at baseline and follow up visits: free heme level

    Time frame: 10 years

  7. Potential biological risk marker measured at baseline and follow up visits: inflammatory cytokines

    Time frame: 10 years

  8. Potential biological risk marker measured at baseline and follow up visits: neutrophil extracellular traps

    Time frame: 10 years

06

Study locations

10 of 13 sites recruiting
  • Central Hospital of Yaounde
    Yaounde, Cameroon
    • Françoise Ngo Sacks, MD · Contact
    • Samuel Kingue, MD · Principal investigator
    • Françoise Ngo Sacks, MD · Sub investigator
    Recruiting
  • Centre mère et enfant / fondation Chantal Biya
    Yaounde, Cameroon
    • David Chelo, MD · Contact
    • David Chelo, MD · Principal investigator
    • Anasthasie Alima, MD · Sub investigator
    Recruiting
  • Centre Pasteur du Cameroun
    Yaounde, Cameroon
    • Suzanne Belinga, MD · Contact
    • Suzanne Belinga, MD · Principal investigator
    Recruiting
  • Pediatrics unit, Centre Hospitalier d'Essos
    Yaounde, Cameroon
    • guillaume Wamba, MD · Contact
    • Guillaume Wamba, MD · Principal investigator
    Recruiting
  • Centre hospitalier Monkole
    Kinshasa, Congo, The Democratic Republic of the
    • Leon Tshilolo, MD · Contact
    • Leon Tshilolo, MD · Principal investigator
    Recruiting
  • Hematology Unit, CHU Yopougon
    Abidjan, Côte D'Ivoire
    • Aissata Tolo, MD · Contact
    • Aissata Tolo, MD · Principal investigator
    • Kouakou Boidy, MD · Sub investigator
    Recruiting
  • Institut de cardiologie
    Abidjan, Côte D'Ivoire
    Active, not 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
    • Dapa Diallo, MD · Contact
    • Dapa Diallo, MD · Principal investigator
    • Karim Dembele, MD · Sub investigator
    Recruiting
  • Centre hospitalier d'enfants Albert Royer
    Dakar, Senegal
    • Ibrahima Diagne, MD · Contact
    • Ibrahima Diagne, MD · Principal investigator
    • Indou Deme-Ly, MD · Sub investigator
    Recruiting
  • Centre hospitalo-universotaire de Fann, Cardiology department
    Dakar, Senegal
    • Bara Diop, MD · Contact
    • Bara Diop, MD · Principal investigator
    Recruiting
  • Centre national de transfusion sanguine
    Dakar, Senegal
    • Saliou Diop, MD · Contact
    • Saliou Diop, MD · Principal investigator
    Recruiting
07

References and documents

Publications

  • 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. PubMed 17084951 ↗
  • 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. PubMed 21264896 ↗
  • 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. PubMed 22983573 ↗
  • 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. PubMed 20884713 ↗
  • 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. PubMed 20833087 ↗
  • 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. PubMed 18461136 ↗
  • 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. PubMed 14985486 ↗
  • 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. PubMed 16291595 ↗
  • 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. PubMed 24223994 ↗
  • 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. PubMed 15985542 ↗
  • 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. PubMed 16755569 ↗
  • 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. PubMed 22641398 ↗
  • 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. PubMed 27582423 ↗
  • 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. PubMed 27030156 ↗
  • 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. PubMed 33249569 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03114137
Lead sponsor
Cardiologie et Développement
Collaborators
Institut National de la Santé Et de la Recherche Médicale, France, University of Paris 5 - Rene Descartes, laboratory of excellence GR-Ex
Responsible party
Xavier Jouven (Professor, Cardiologie et Développement) — Principal investigator
First posted
Apr 14, 2017
Start date
Mar 2012
Primary completion
Dec 2020 (estimated)
Completion
Dec 2022 (estimated)
Last update
May 25, 2018

Study contacts

Brigitte Ranque, MD PhD
Contact
brigitte.ranque@aphp.fr
Louise Boyer-Chatenet, MS
Contact
louise.boyer-chatenet-ext@aphp.fr
+33156093656
Xavier Jouven, MD PhD
principal investigator · Cardiologie et Developpement

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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