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

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ClinicalTrials.gov Identifier: NCT02890134
Recruitment Status : Unknown
Verified August 2016 by Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud ( Fundación Pública Andaluza Progreso y Salud ).
Recruitment status was:  Recruiting
First Posted : September 7, 2016
Last Update Posted : December 12, 2016
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 Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud ( Fundación Pública Andaluza Progreso y Salud )

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.

Condition or disease
Systemic Autoimmune Diseases

Detailed Description:

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:

  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 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. 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:

  1. assign individuals newly diagnosed with an systemic autoimmune disease (SAD) to any of the reclassification clusters discovered in the CS study,
  2. 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
  3. 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.


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Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Molecular Reclassification to Find Clinically Useful Biomarkers for Systemic Autoimmune Diseases: Inception Cohort
Study Start Date : June 2015
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : January 2019

Resource links provided by the National Library of Medicine





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


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 depletative therapy such as Rituximab in the last year
    • Patients receiving experimental
    • Overlap syndromes

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): NCT02890134


Contacts
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Contact: Marta Alarcon marta.alarcon@genyo.es
Contact: Jacques-Olivier Pers

Locations
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Belgium
Université catholique de Louvain - Cliniques Universitaires Saint-Luc (UCL) Recruiting
Brussels, Belgium
Contact: Bernard Lauwerys       bernard.lauwerys@uclouvain.be   
UZ Leuven - KU Leuven, Department of Rheumatology (KU LEUVEN) Recruiting
Leuven, Belgium
Contact: Rik Lories       rik.lories@kuleuven.be   
France
CHRU de Brest Recruiting
Brest, France, 29609
Contact: Alain SARAUX       alain.saraux@chu-brest.fr   
Germany
Deutsches Rheuma-Forschungszentrum Berlin (DRFZ) Recruiting
Berlin, Germany
Contact: Falk Hiepe       falk.hiepe@charite.de   
Italy
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico (IRCCS) Recruiting
Milan, Italy
Contact: Lorenzo Beretta       lorberimm@hotmail.com   
Spain
Hospital Clinic I Provicia- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Recruiting
Barcelona, Spain
Contact: Ricard Cervera       rcervera@clinic.cat   
Hospital Universitario Reina Sofía Andaluz de Salud Recruiting
Cordoba, Spain
Contact: Eduardo Collantes       educollantes@yahoo.es   
Hospital Universitario San Cecilio Servicio Andaluz de Salud Recruiting
Granada, Spain
Contact: Norberto Ortego       norberto@gmail.com   
Hospital Virgen de las Nieves Granada Recruiting
Granada, Spain
Contact: Enrique Raya       enriraya@gmail.com   
Switzerland
Hospitaux Universitaires de Géneve (UNIGE) Recruiting
Geneve, Switzerland
Contact: Carlo Chizzolini       Carlo.Chizzolini@unige.ch   
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)

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Responsible Party: Fundación Pública Andaluza Progreso y Salud
ClinicalTrials.gov Identifier: NCT02890134     History of Changes
Other Study ID Numbers: PRECISESADS INCP (RB 15.007)
First Posted: September 7, 2016    Key Record Dates
Last Update Posted: December 12, 2016
Last Verified: August 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud ( Fundación Pública Andaluza Progreso y Salud ):
SADs
Molecular Reclassification
Additional relevant MeSH terms:
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Autoimmune Diseases
Immune System Diseases