Integrative Diagnosis for SCD and Other RADs (INTEGRA)

Vall d'Hebron University Hospital (HUVH)

Status: Enrolling

Conditions: Hemoglobin Disorder; Congenital Dyserythropoietic Anemia (CDA); Stomatocytosis; Rare Anemia Disorders; Thalassaemia; Spherocytosis, Hereditary; Sickle Cell Disease; Anemia Due to Membrane Defect; Enzyme Disorder; Anemia

Treatments: Diagnostic Test: Disease phenotyping; Genetic: Analysis of genetic modifiers

Study type: Observational

Funder types: Other

Identifiers

NCT07206095

Evidence 860436 (Other Grant/Funding Number)

Integra-SCD PI20/01454 (Other Grant/Funding Number)

GA 101095530 - SYNTHEMA (Other Grant/Funding Number)

GA 101017549 - GENOMED4ALL (Other Grant/Funding Number)

PR(AMI)427/2021

PR(AMI)543/2020

Details and patient eligibility

About

INTEGRA aims at enabling personalized medicine for RHADs patients by the establishment of an integrative diagnostic approach based on deep phenotypic and genetic characterization through combining new generation methodologies.

Full description

Objectives:

• To assess the prognostic value of LoRRca (ektacytometry) as biomarker providing information of SCD/RADs patients severity
• To investigate the correlation between LoRRca parameters and SCD/RADs patients genetic and phenotypic characterization.
• To identify genetic modifiers of RADs both new and previously described by GWAS as markers for prognosis and clinical course based on genomics approach.
• To establish an innovative algorithm for RADs patients characterization based on the integration of data generated through the analysis of genetic modifiers and the RBCs rheological properties by LoRRca profiles and microfluidics data in combination with RADs patients' clinical manifestations and treatments.
• To model the progression of RADs in a spleen-like filtering unit using microfluidic technologies to develop a novel diagnostic device for prognosis and patients' stratification. This device will be used for the characterization under flow of rheological and mechanical properties of single RBCs.
• To translate the results on a clinical practice recommendation for management of RADs patients endorsed by European Hematology bodies as ERN-EuroBloodNet and/or the European Hematology Association for its wide dissemination.

Enrollment: 200 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients sustaining a confirmed or suspected diagnosis of an hereditary rare hemolytic anemia:
• Sickle cell disease
• Thalassemic syndromes
• Congenital dyserythropoietic anemia
• Enzymopathy
• Unstable Hemoblogin / Altered oxygen affinity
• Hereditary stomatocytosis
• Hereditary pyropoikilocytosis
• Hereditary spherocytosis with severe anemia (<8 g/dL) or inconclusive diagnosis:
• Patient with chronic hemolytic anemia and red cell smear compatible, but with:
• EMA binding test: inconclusive or negative
• Genetic testing: no definitive diagnosis (VUS or no findings)
• Not transplanted or undergoing gene therapy at the time of inclusion. Patients with graft failure without a new transplant may be included.

Exclusion criteria

• Carrier traits in autosomal recessive hereditary anemias