Molecular Reclassification to Find Clinically Useful Biomarkers for Systemic Autoimmune Diseases: Inception Cohort (PRECISESADSI)
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|ClinicalTrials.gov Identifier: NCT02890134|
Recruitment Status : Completed
First Posted : September 7, 2016
Last Update Posted : October 15, 2021
|Condition or disease|
|Systemic Autoimmune Diseases|
The overall objective of the PRECISESADS IMI project is to reclassify the individuals affected by SADs into clusters of molecular, instead of clinical entities through the determination of molecular profiles using several "-omics" techniques.
The identification of the clusters relies on a cross sectional (CS) cohort/protocol where 2666 individuals (2000 patients and 666 controls) including a sub-study of 288 deeply characterized individuals (240 patients and 48 controls) are to be recruited.
In parallel a longitudinal inception cohort/protocol will be started in order to further explore the clinical relevance of the identified clusters and their evolution over time.
The objectives of the CS study and sub-study are:
- To identify a systemic taxonomy for patients with SADs by producing the following data in individuals with SADs and controls: genetic, epigenomic, transcriptomic, flow cytometric (from peripheral blood mononuclear cells (PBMCs)), metabolomics and proteomic in plasma and urine, exosome analysis, classical serology (antibodies and autoantibodies), and clinical data.
- To better characterize individual SADs at the omics level.
- To perform clustering analyses to determine the groups of individuals who, differentially from other groups, share specific molecular features (precision medicine).
- A deeper analysis will be done in a substudy of 288 individuals.
The clustering process will be data-driven with the aim to find the most homogenous and differentiated clusters of diseases that clearly separate differentiate individuals from controls and other patient clusters.
Aims of the Inception cohort:
Specifically, this inception cohort aims at:
- assign individuals newly diagnosed with an systemic autoimmune disease (SAD) to any of the reclassification clusters discovered in the CS study,
- to study the development and modifications of OMICS signatures/clusters occurring in each individual patient in the course of the disease, including the impact of treatment on their individual pattern, and
- to perform deep (thorough) OMICs studies to compare their patterns of OMICS as a group, with the patterns obtained in the CS cohort.
The inception cohort will have patient follow up and sample collection at baseline, month 6(±1 month) and month 18 (±1 month).
As the newly diagnosed patients we plan to recruit will have minimum or no treatment, we will identify differences and similitudes to patients from the cross-sectional study that have undergone long-term treatment.
|Study Type :||Observational|
|Actual Enrollment :||215 participants|
|Official Title:||Molecular Reclassification to Find Clinically Useful Biomarkers for Systemic Autoimmune Diseases: Inception Cohort|
|Study Start Date :||June 2015|
|Actual Primary Completion Date :||July 2018|
|Actual Study Completion Date :||July 2018|
- Gene expression in total blood [ Time Frame: 2 years ]Gene expression will be done using commercial gene expression microarrays in total blood from all samples using the RNA Paxgene tube.
- Flow cytometry analysis to determine cell proportions in the total blood mixture in all individuals. [ Time Frame: 24 hours ]9 optimized panels of antibodies will be used to determine cell subpopulations in peripheral blood (including very minor cell populations).
- Genotyping [ Time Frame: 2 years ]Genotyping will be done using a whole genome array.
- Metabolite determination [ Time Frame: 2 years ]Metabolite determination in plasma and urine using Nuclear Magnetic Resonance
- Exosome isolation from plasma and urine [ Time Frame: 2 years ]set up of the methodology for isolating exosomes in these bodily fluids for gene expression analysis
- Cytokine profile determination [ Time Frame: 2 years ]88 different cytokines will be assessed with Luminex
- routine autoantibodies in serum [ Time Frame: 2 years ]set of serum autoantibodies will be determined in a European validated laboratory. Also, they will perform detection of antibodies against small lipid moieties i.e.antiphosphorylcholine),lupus anticoagulant and complement proteins in plasma.
- Gene methylation in total blood [ Time Frame: 2 years ]Methylation analysis will be done using the methylome 450k array using the DNA obtained from total blood. MicroRNA gene expression arrays using total blood.
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02890134
|Université catholique de Louvain - Cliniques Universitaires Saint-Luc (UCL)|
|UZ Leuven - KU Leuven, Department of Rheumatology (KU LEUVEN)|
|CHRU de Brest|
|Brest, France, 29609|
|Deutsches Rheuma-Forschungszentrum Berlin (DRFZ)|
|Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico (IRCCS)|
|Hospital Clinic I Provicia- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)|
|Hospital Universitario Reina Sofía Andaluz de Salud|
|Hospital Universitario San Cecilio Servicio Andaluz de Salud|
|Hospital Virgen de las Nieves Granada|
|Hospitaux Universitaires de Géneve (UNIGE)|
|Study Director:||Marta Alarcon||Fundación Pública Andaluza Progreso y Salud (PHFSpain)|