Molecular Reclassification to Find Clinically Useful Biomarkers for Systemic Autoimmune Diseases: (PRECISESADS)
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|ClinicalTrials.gov Identifier: NCT02890121|
Recruitment Status : Completed
First Posted : September 7, 2016
Last Update Posted : May 23, 2018
|Condition or disease|
|Systemic Autoimmune Diseases|
The main objective of the PRECISESADS project is to reclassify the individuals affected by SADs into molecular clusters instead of clinical entities through the determination of molecular profiles using several "-omics" techniques.
The specific objectives of this cross sectional 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 and polymorphonuclear 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).
- To identify gene expression, methylation profiles through deconvolution methods comparing a mixture of cells with subpopulations determined by flow cytometry with separated cells, cytokine profiles and plasma metabolomics using Mass Spectrometry, 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 individuals on the basis of, serological, genetic, epigenomic, cellular (cell proportions), metabolomic, proteomic (cytokines, autoantibodies) and transcriptome characteristics and differentiate them from controls and other patient clusters.
A total of 2000 patients and 666 controls will be included in the study, adjusted to the following distribution:
- A total of 400 patients diagnosed with systemic lupus erythematosus (SLE)
- A total of 400 patients diagnosed with rheumatoid arthritis (RA)
- A total of 400 patients diagnosed of scleroderma or systemic sclerosis (SSc)
- A total of 400 patients diagnosed of Sjögren's syndrome (SjS)
- A total of 400 patients diagnosed of primary antiphospholipid syndrome (PAPS) or Mixed Connective Tissue Disease (MCTD) or with undifferentiated disease • All patients will be recruited from 18 sites in Europe (Austria, Belgium, France, Germany, Italy, Portugal, Spain, Hungary and Switzerland).
|Study Type :||Observational|
|Actual Enrollment :||2006 participants|
|Official Title:||Molecular Reclassification to Find Clinically Useful Biomarkers for Systemic Autoimmune Diseases: Cross Sectional Cohort|
|Actual Study Start Date :||December 2014|
|Actual Primary Completion Date :||October 2017|
|Actual Study Completion Date :||October 2017|
- 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): NCT02890121
|Study Director:||Marta Alarcon||Fundación Pública Andaluza Progreso y Salud (PHFSpain)|