An observational study in Sickle Cell Disease, sponsored by Cardiologie et Développement. Status unknown at 2 sites in 2 countries. Open to participants aged 10 Years and older. Per ClinicalTrials.gov, last updated 2017-11-24.
Sponsored by Cardiologie et Développement · Observational
BIOCADRE is a CADRE substudy and aims to characterize more precisely the sickle cell patients with extreme phenotype.
Sickle cell disease (SCD) is the most frequent monogenic disease in the world, due to a unique mutation on the β-globin gene. Most affected individuals live in sub-Saharan Africa, yet, the natural history of the disease in Africa remains largely unknown. SCD usually presents in childhood and is characterized by the association of a chronic hemolytic anemia with episodes of acute vaso-occlusive events and progressive vascular organ damage. SCD is now widely recognized as a vascular disease with marked endothelial dysfunction. Hemolysis probably plays a key role by reducing NO bioavailability, but other involved mechanisms are not fully understood.
The project aims at better understanding SCD chronic vascular complications and in particular to explore extensively the different mechanisms associated with hemolysis. This will be addressed through both an epidemiological approach and a hypotheses-driven pathophysiological approach. On the one hand, a descriptive and analytic epidemiological study will isolate clusters of clinical, functional and usual biological phenotypes in SCD patients and look for new mechanistic and biological markers predictive of chronic vascular complications in SCD with SS phenotype. Investigators will specifically investigate i) microcirculation functions using peripheral arterial tonometry, ii) blood and plasma viscosities, iii) level of plasma blood cell derived microparticles, free hemoglobin, and the free heme content of erythrocytes-derived microparticles and expression of Duffy erythrocyte antigen, the unique erythroid receptor for chemokines. One the other hand, investigators will test novel markers and modifiers of hemolysis and heme metabolism and assess their relationship with inflammation and vascular phenotypes.These different biomarkers will be compared between the selected subgroups of patients with extreme vascular phenotype.
Methods: The project involves a transversal case control study, nested in the CADRE cohort, recently built up by Partner 1 and African collaborators. CADRE is the largest ongoing epidemiological cohort, including 4,300 SCD patients and 1,000 controls in five west and central African countries, in which various chronic complications of SCD have already been registered. The present second phase study will be conducted in the centres of Dakar and Bamako. Patients' selection will be performed in the existing database to obtain 6 subgroups of 40 SS patients with one of the main vascular chronic complications or none of them, for a total of 240 patients. Selected patients will be recalled during one year in parallel in the 2 recruiting centres. Clinical phenotyping, usual biology, functional microvascular functions (peripheral arterial tonometry), and blood/plasma viscosities analyses will be performed in the African recruiting centres after training of technicians, PhD and MD students by the French partners. Plasma samples, microparticles and extracellular DNA, will be prepared and frozen for further analyses in the partner's laboratories. DNA will be collected for each subject. A principal component analysis will isolate clusters of clinical complications, functional and biological markers and a multivariate logistic regression will quantify the effect of these markers on the risk of vasculopathy, with adjustment on all known SCD modifying factors.
Expected results: 1) The identification of high risk SCD patients for chronic vascular complications using new biomarkers, 2) A better understanding of chronic vascular disease process at the mechanistic and biological (viscosity, hemolysis, erythrocyte derived microparticles, inflammatory cytokines and receptors) levels, 3) The identification of endophenotypes and constitution of DNA bank for further genetic studies.
1,134 studies on the registry are indexed under Anemia, Sickle Cell; 238 are open to participants now.
This study's planned enrollment of 300 is above the median of 100 across 296 observational studies indexed under Anemia, Sickle Cell.
Browse Anemia, Sickle Cell studies →Cardiologie et Développement is the lead sponsor of 3 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
The study population is sickle cell patients with extreme phenotypes (SS-hemoglobin) with a steady state.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Sickle cell patients with osteonecrosis as a vascular main complication
Biological: biological analysis · Other: peripheral arterial tonometry
Sickle cell patients with leg ulcer as a vascular main complication
Biological: biological analysis · Other: peripheral arterial tonometry
Sickle cell patients with microalbuminuria as a vascular main complication
Biological: biological analysis · Other: peripheral arterial tonometry
Sickle cell patients with pulmonary hypertension as a vascular main complication
Biological: biological analysis · Other: peripheral arterial tonometry
Sickle cell patients with strocke as a vascular main complication
Biological: biological analysis · Other: peripheral arterial tonometry
Sickle cell patients with priapism as a vascular main complication
Biological: biological analysis · Other: peripheral arterial tonometry
biological analysis will be performed in the 6 groups of patients
peripheral arterial tonometry will be performed in the 6 groups of patients
Description of microcirculation by peripheral arterial tonometry
EndoPAT2000®, Itamar Medical Ltd,
Time frame: 1 year
Measure of blood viscosities
In whole blood by viscosimeter
Time frame: 1 year
Dosage of microparticles
In plasma: microparticles of erythrocytic, platelet, monocytic, neutrophilic and endothelial origin by flow cytometry
Time frame: 1 year
Determination of free hemoglobin
In plasma
Time frame: 1 year
Measurement of neutrophil extracellular trap (NET)
In plasma
Time frame: 1 year
Measurement of proinflammatory cytokines by ELISA
In plasma by ELISA
Time frame: 1 year
Genotyping of the alpha-globin gene associated with persistence of fetal hemoglobin
In saliva DNA
Time frame: 1 year
Genotyping of the polymorphisms associated with persistence of fetal hemoglobin
In saliva DNA
Time frame: 1 year
Plan to share: No
Started May 2017 (actual). Primary completion is estimated for Jun 2019, 25 months after the start.
Of 130 non-industry observational studies under Anemia, Sickle Cell, half reached primary completion within 48 months of starting (the median), counting those still running; a quarter within 23 and three quarters within 109. This study's planned 25 months is below that.
Counting every sponsor, half of 139 studies reached it within 49 months; a quarter within 24 and three quarters within 109.
How these figures are worked out, and which studies are left out of them.
This study is status unknown, as verified in Nov 2017. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Cardiologie et Développement