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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
Sponsor:
Collaborators:
UCB Biopharma S.P.R.L.
Atrys Health
National Research Council, Spain
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Servicio Cántabro de Salud
August Pi Sunyer Biomedical Research Institute
Karolinska Institutet
KU Leuven
Klinikum der Universität Köln
Hannover Medical School
Medical University of Vienna
Quartz Bio S.A.
Andaluz Health Service
The Cyprus Foundation for Muscular Dystrophy Research
Universidad de Granada
University of Milan
Université Catholique de Louvain
University Hospital, Brest
University of Geneva, Switzerland
Szeged University
Bayer
Institut de Recherches Internationales Servier
Sanofi
Eli Lilly and Company
Charite University, Berlin, Germany
Centro Hospitalar do Porto
Institut d'Investigació Biomèdica de Bellvitge
Innovative Medicines Initiative
Information provided by (Responsible Party):
Andalusian Network for Design and Translation of Advanced Therapies ( Fundación Pública Andaluza Progreso y Salud )

Study Description
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Brief Summary:
Connective tissue diseases (CTD) or systemic autoimmune diseases (SADs) as they are known today are a group of chronic inflammatory conditions with autoimmune aetiology with few treatment options and difficult diagnosis.Brest team contribute to perform a new classification of the following systemic autoimmune diseases in a European Union's Seventh Framework Programme. The aim of this research 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.

Condition or disease
Systemic Autoimmune Diseases

Detailed Description:

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:

  1. 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.
  2. To better characterize individual SADs at the omics level.
  3. To perform clustering analyses to determine the groups of individuals who, differentially from other groups, share specific molecular features (precision medicine).
  4. 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 Design
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Study Type : Observational
Actual Enrollment : 2006 participants
Observational Model: Cohort
Time Perspective: Prospective
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

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. 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).

  3. Genotyping [ Time Frame: 2 years ]
    Genotyping will be done using a whole genome array

  4. Metabolite determination [ Time Frame: 2 years ]
    Metabolite determination in plasma and urine using Nuclear Magnetic Resonance

  5. 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

  6. Cytokine profile determination [ Time Frame: 2 years ]
    88 different cytokines will be assessed with Luminex

  7. 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.

  8. 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
Blood and urine

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patient with systemic autoimmune diseases
Criteria

Inclusion Criteria:

  • · Aged 18 years or older at the time of consent

    • Diagnosed according to prevailing criteria for one of the following systemic autoimmune diseases (see Annex 2)

      • Rheumatoid arthritis (RA)
      • Scleroderma or systemic sclerosis (SSc)
      • Primary Sjögren's syndrome (SjS)
      • Systemic lupus erythematosus (SLE)
      • Primary antiphospholipid syndrome (PAPS)
      • Mixed Connective Tissue Disease (MCTD)
      • Patients with undifferentiated connective tissue disease (UCTD) for over 1 year and that do not fulfill the diagnosis of any of the above diseases.
    • Signed the informed consent form

Exclusion Criteria:

  • · Patients unable to understand the procedures related to the protocol should not be included. The study is voluntary and patients must be able to give their informed consent.

    • Pregnant women
    • Neonatal lupus
    • Drug-induced lupus
    • Patients whose condition is so serious that they cannot take part in the study
    • Severe nephrotic syndrome with proteinuria >=3,5 g/day
    • Patients with stable doses of steroids >15mg/day for the last 3 months or with IV corticosteroids in the last 3 months

    • Patients under immunosuppressants for the last 3 months prior to recruitment with:

      • Methotrexate ≥25mg/week
      • Azathioprine ≥2.5mg/kg/day
      • Cyclosporine A > 3mg/kg/day
      • Mycophenolate Mofetil > 2gr/day
    • Treatment with cyclophosphamide (any dose or route of administration) or Belimumab in the past 6 months
    • Patients with combined therapy of two or more immunosuppressants
    • Patients on depletive therapy such as Rituximab in the last year
    • Patients receiving experimental therapy.
    • Chronic HBV or HCV infection
    • Overlap syndromes
Contacts and Locations
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Information from the National Library of Medicine

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


Locations
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Sponsors and Collaborators
Fundación Pública Andaluza Progreso y Salud
UCB Biopharma S.P.R.L.
Atrys Health
National Research Council, Spain
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Servicio Cántabro de Salud
August Pi Sunyer Biomedical Research Institute
Karolinska Institutet
KU Leuven
Klinikum der Universität Köln
Hannover Medical School
Medical University of Vienna
Quartz Bio S.A.
Andaluz Health Service
The Cyprus Foundation for Muscular Dystrophy Research
Universidad de Granada
University of Milan
Université Catholique de Louvain
University Hospital, Brest
University of Geneva, Switzerland
Szeged University
Bayer
Institut de Recherches Internationales Servier
Sanofi
Eli Lilly and Company
Charite University, Berlin, Germany
Centro Hospitalar do Porto
Institut d'Investigació Biomèdica de Bellvitge
Innovative Medicines Initiative
Investigators
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Study Director: Marta Alarcon Fundación Pública Andaluza Progreso y Salud (PHFSpain)
More Information
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Responsible Party: Fundación Pública Andaluza Progreso y Salud
ClinicalTrials.gov Identifier: NCT02890121    
Other Study ID Numbers: PRECISESADS CS (RB 14.106)
First Posted: September 7, 2016    Key Record Dates
Last Update Posted: May 23, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Andalusian Network for Design and Translation of Advanced Therapies ( Fundación Pública Andaluza Progreso y Salud ):
SADs
Molecular Reclassification
Additional relevant MeSH terms:
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Autoimmune Diseases
Immune System Diseases