Heart Arteries and Sickle Cell Disease / Coeur Artères DREpanocytose

Sickle Cell Disease Clinical Trial

— CADRE  

Official title:

Heart, Arteries and Sikle Cell Disease, a Multicentric Cohort of Cardiovascular Complications in Subsaharan Africa

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03114137
• Other study ID #: 002
• Status: Recruiting
• Start date: March 2012
• Est. completion date: December 2022

Study information

• Verified date: May 2018
• Source: Cardiologie et Développement
• Contact: Brigitte Ranque, MD PhD
• Email: brigitte.ranque[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 4500
• Est. completion date: December 2022
• Est. primary completion date: December 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 5 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Anemia
• Sickle Cell Disease

Locations

Country	Name	City	State
Cameroon	Central Hospital of Yaounde	Yaounde
Cameroon	Centre mère et enfant / fondation Chantal Biya	Yaounde
Cameroon	Centre Pasteur du Cameroun	Yaounde
Cameroon	Pediatrics unit, Centre Hospitalier d'Essos	Yaounde
Congo, The Democratic Republic of the	Centre hospitalier Monkole	Kinshasa
Côte D'Ivoire	Hematology Unit, CHU Yopougon	Abidjan
Côte D'Ivoire	Institut de cardiologie	Abidjan
Gabon	CIRMF	Libreville
Mali	Cardiology Unit, Centre gyneco-obstretrique	Bamako
Mali	Centre de Recherche et de Lutte contre la Drepanocytose	Bamako
Senegal	Centre hospitalier d'enfants Albert Royer	Dakar
Senegal	Centre hospitalo-universotaire de Fann, Cardiology department	Dakar
Senegal	Centre national de transfusion sanguine	Dakar

Sponsors (4)

Lead Sponsor	Collaborator
Cardiologie et Développement	Institut National de la Santé Et de la Recherche Médicale, France, laboratory of excellence GR-Ex, University of Paris 5 - Rene Descartes

Countries where clinical trial is conducted

Cameroon,  Congo, The Democratic Republic of the,  Côte D'Ivoire,  Gabon,  Mali,  Senegal, 

References & Publications (14)

Connes P, Lamarre Y, Hardy-Dessources MD, Lemonne N, Waltz X, Mougenel D, Mukisi-Mukaza M, Lalanne-Mistrih ML, Tarer V, Tressières 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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. Epub 2006 Nov 7. Review. — View Citation

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. — View Citation

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. Epub 2005 Nov 15. — View Citation

Maier-Redelsperger M, Lévy P, Lionnet F, Stankovic K, Haymann JP, Lefèvre 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. — View Citation

Nolan VG, Wyszynski DF, Farrer LA, Steinberg MH. Hemolysis-associated priapism in sickle cell disease. Blood. 2005 Nov 1;106(9):3264-7. Epub 2005 Jun 28. — View Citation

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. — View Citation

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 Jeun — View Citation

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 — View Citation

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. Review. — View Citation

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. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence and 10 year-incidence of SCD-related vascular complications in different phenotypes of SCD: glomerulopathy	urinary albumin/creatinin ratio (mg/g)	10 years
Primary	Prevalence and 10 year-incidence of SCD-related vascular complications in different phenotypes of SCD: cardiopathy	left ventricular ejection fraction < 60 %	10 years
Primary	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
Primary	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
Primary	Prevalence and 10 year-incidence of SCD-related vascular complications in different phenotypes of SCD:stroke	clinical diagnosis	10 years
Primary	Prevalence and 10 year-incidence of SCD-related vascular complications in different phenotypes of SCD:osteonecrosis	standard radiography	10 years
Primary	Prevalence and 10 year-incidence of SCD-related vascular complications in different phenotypes of SCD: leg ulcers	clinical diagnosis	10 years
Primary	Prevalence and 10 year-incidence of SCD-related vascular complications in different phenotypes of SCD: priapism	clinical diagnosis	10 years
Secondary	Potential biological risk marker measured at baseline and follow up visits: carotid-femoral pulse wave velocity	measured by Pulsepen, m/s)	10 years
Secondary	Potential biological risk marker measured at baseline and follow up visits: complete blood count		10 years
Secondary	Potential biological risk marker measured at baseline and follow up visits: LDH level		10 years
Secondary	Potential biological risk marker measured at baseline and follow up visits: bilirubin level		10 years
Secondary	Potential biological risk marker measured at baseline and follow up visits: microparticules measure		10 years
Secondary	Potential biological risk marker measured at baseline and follow up visits: free heme level		10 years
Secondary	Potential biological risk marker measured at baseline and follow up visits: inflammatory cytokines		10 years
Secondary	Potential biological risk marker measured at baseline and follow up visits: neutrophil extracellular traps		10 years