Molecular Reclassification to Find Clinically Useful Biomarkers for Systemic Autoimmune Diseases: Inception Cohort

NCT02890134 | Completed DMC

• 1 other identifier: PRECISESADS INCP (RB 15.007)
• Study Type: observational
• Target: 215
• Locations: 6 countries
• Sites: 10

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 performe a new classification of the following systemic autoimmune diseases in a European Union's Seventh Framework Programme. The aim of this research consiteis to reclassify the individuals affected by SADs into molecular clusters instead of clinical entities through the determination of molecular profiles using several "Omics" techniques.

Conditions

Systemic Autoimmune Diseases

Keywords

SADs; Molecular Reclassification

Outcome Measures

Primary Outcomes (8)

• Gene expression in total blood

  Gene expression will be done using commercial gene expression microarrays in total blood from all samples using the RNA Paxgene tube.

  2 years

• Flow cytometry analysis to determine cell proportions in the total blood mixture in all individuals.

  9 optimized panels of antibodies will be used to determine cell subpopulations in peripheral blood (including very minor cell populations).

  24 hours

• Genotyping

  Genotyping will be done using a whole genome array.

  2 years

• Metabolite determination

  Metabolite determination in plasma and urine using Nuclear Magnetic Resonance

  2 years

• Exosome isolation from plasma and urine

  set up of the methodology for isolating exosomes in these bodily fluids for gene expression analysis

  2 years

• Cytokine profile determination

  88 different cytokines will be assessed with Luminex

  2 years

• routine autoantibodies in serum

  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.

  2 years

• Gene methylation in total blood

  Methylation analysis will be done using the methylome 450k array using the DNA obtained from total blood. MicroRNA gene expression arrays using total blood.

  2 years

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patient with systemic autoimmune diseases

You may qualify if:

• · 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

You may not qualify if:

• · 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 depletative therapy such as Rituximab in the last year

Sponsors & Collaborators

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

Study Sites (10)

Université catholique de Louvain - Cliniques Universitaires Saint-Luc (UCL)

Brussels, Belgium

Location

UZ Leuven - KU Leuven, Department of Rheumatology (KU LEUVEN)

Leuven, Belgium

Location

CHRU de Brest

Brest, 29609, France

Location

Deutsches Rheuma-Forschungszentrum Berlin (DRFZ)

Berlin, Germany

Location

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico (IRCCS)

Milan, Italy

Location

Hospital Clinic I Provicia- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)

Barcelona, Spain

Location

Hospital Universitario Reina Sofía Andaluz de Salud

Córdoba, Spain

Location

Hospital Universitario San Cecilio Servicio Andaluz de Salud

Granada, Spain

Location

Hospital Virgen de las Nieves Granada

Granada, Spain

Location

Hospitaux Universitaires de Géneve (UNIGE)

Geneva, Switzerland

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood and urine

Study Officials

• Marta Alarcon

  Fundación Pública Andaluza Progreso y Salud (PHFSpain)

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2016
• First Posted: September 7, 2016
• Study Start: June 1, 2015
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: October 15, 2021

Record last verified: 2016-08

Locations

FR (1); CH (1); BE (2); ES (4); DE (1); IT (1)