Substudy of CADRE: for People With Extreme Phenotype: BIOCADRE (BIOCADRE)

November 22, 2017 updated by: Cardiologie et Développement

A Substudy of the CADRE Study: Determination of Clinical Markers in Patients With Extreme Sickle Cell Disease Phenotype

BIOCADRE is a CADRE substudy and aims to characterize more precisely the sickle cell patients with extreme phenotype.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Observational

Enrollment (Anticipated)

300

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Mali
      • Bamako, Mali
        • Recruiting
        • Centre de Recherches er de Lutte contre la Drépanocytose
        • Principal Investigator:
          • Dapa Diallo, MD
        • Contact:
  • Senegal
      • Dakar, Senegal
        • Recruiting
        • Centre National de Transfusion Sanguine
        • Principal Investigator:
          • Saliou Diop, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The study population is sickle cell patients with extreme phenotypes (SS-hemoglobin) with a steady state.

Description

Inclusion Criteria:

  • sickle cell patients with extreme phenotypes: SS-hemoglobin

Exclusion Criteria:

  • transfusion in the previous 2 months
  • vaso-occlusive crisis in the previous 15 days
  • infection in the previous 8 days

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
osteonecrosis
Sickle cell patients with osteonecrosis as a vascular main complication
Biological: biological analysis
biological analysis will be performed in the 6 groups of patients
Other: peripheral arterial tonometry
peripheral arterial tonometry will be performed in the 6 groups of patients
leg ulcer
Sickle cell patients with leg ulcer as a vascular main complication
Biological: biological analysis
biological analysis will be performed in the 6 groups of patients
Other: peripheral arterial tonometry
peripheral arterial tonometry will be performed in the 6 groups of patients
microalbuminuria
Sickle cell patients with microalbuminuria as a vascular main complication
Biological: biological analysis
biological analysis will be performed in the 6 groups of patients
Other: peripheral arterial tonometry
peripheral arterial tonometry will be performed in the 6 groups of patients
pulmonary hypertension
Sickle cell patients with pulmonary hypertension as a vascular main complication
Biological: biological analysis
biological analysis will be performed in the 6 groups of patients
Other: peripheral arterial tonometry
peripheral arterial tonometry will be performed in the 6 groups of patients
stroke
Sickle cell patients with strocke as a vascular main complication
Biological: biological analysis
biological analysis will be performed in the 6 groups of patients
Other: peripheral arterial tonometry
peripheral arterial tonometry will be performed in the 6 groups of patients
priapism
Sickle cell patients with priapism as a vascular main complication
Biological: biological analysis
biological analysis will be performed in the 6 groups of patients
Other: peripheral arterial tonometry
peripheral arterial tonometry will be performed in the 6 groups of patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Description of microcirculation by peripheral arterial tonometry
Time Frame: 1 year
EndoPAT2000®, Itamar Medical Ltd,
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measure of blood viscosities
Time Frame: 1 year
In whole blood by viscosimeter
1 year
Dosage of microparticles
Time Frame: 1 year
In plasma: microparticles of erythrocytic, platelet, monocytic, neutrophilic and endothelial origin by flow cytometry
1 year
Determination of free hemoglobin
Time Frame: 1 year
In plasma
1 year
Measurement of neutrophil extracellular trap (NET)
Time Frame: 1 year
In plasma
1 year
Measurement of proinflammatory cytokines by ELISA
Time Frame: 1 year
In plasma by ELISA
1 year
Genotyping of the alpha-globin gene associated with persistence of fetal hemoglobin
Time Frame: 1 year
In saliva DNA
1 year
Genotyping of the polymorphisms associated with persistence of fetal hemoglobin
Time Frame: 1 year
In saliva DNA
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cardiologie et Développement

Collaborators

Institut National de la Santé Et de la Recherche Médicale, France

Investigators

  • Principal Investigator: Brigitte Ranque, MD, Institut National de la Santé Et de la Recherche Médicale, France

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 15, 2017

Primary Completion (ANTICIPATED)

June 1, 2019

Study Completion (ANTICIPATED)

December 1, 2019

Study Registration Dates

First Submitted

October 10, 2017

First Submitted That Met QC Criteria

November 22, 2017

First Posted (ACTUAL)

November 24, 2017

Study Record Updates

Last Update Posted (ACTUAL)

November 24, 2017

Last Update Submitted That Met QC Criteria

November 22, 2017

Last Verified

November 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 003 (NuSkin International)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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