Clinical trial NCT02890134: Molecular Reclassification to Find Clinically Useful Biomarkers for Systemic Autoimmune Diseases: Inception Cohort
Official title: Molecular Reclassification to Find Clinically Useful Biomarkers for Systemic Autoimmune Diseases: Inception Cohort
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Systemic Autoimmune Diseases
Keywords: SADs
Molecular Reclassification
Lead sponsor: Andalusian Network for Design and Translation of Advanced Therapies
Sponsor class: OTHER
Collaborators: name: UCB Biopharma S.P.R.L.
name: Atrys Health
name: National Research Council, Spain
name: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
name: Servicio Cántabro de Salud
name: August Pi Sunyer Biomedical Research Institute
name: Karolinska Institutet
name: KU Leuven
name: Klinikum der Universität Köln
name: Hannover Medical School
name: Medical University of Vienna
name: Quartz Bio S.A.
name: Andaluz Health Service
name: The Cyprus Foundation for Muscular Dystrophy Research
name: Universidad de Granada
name: University of Milan
name: Université Catholique de Louvain
name: University Hospital, Brest
name: University of Geneva, Switzerland
name: Szeged University
name: Bayer
name: Institut de Recherches Internationales Servier
name: Sanofi
name: Eli Lilly and Company
name: Charite University, Berlin, Germany
name: Centro Hospitalar do Porto
name: Institut d'Investigació Biomèdica de Bellvitge
name: Innovative Medicines Initiative
First posted: 2016-09-07
Enrollment: 215
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patient with systemic autoimmune diseases

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.

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.

Eligibility 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

Primary outcomes:
measure: Gene expression in total blood
timeFrame: 2 years
measure: Flow cytometry analysis to determine cell proportions in the total blood mixture in all individuals.
timeFrame: 24 hours
measure: Genotyping
timeFrame: 2 years
measure: Metabolite determination
timeFrame: 2 years
measure: Exosome isolation from plasma and urine
timeFrame: 2 years
measure: Cytokine profile determination
timeFrame: 2 years
measure: routine autoantibodies in serum
timeFrame: 2 years
measure: Gene methylation in total blood
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Université catholique de Louvain - Cliniques Universitaires Saint-Luc (UCL)
city: Leuven
country: Belgium
facility: UZ Leuven - KU Leuven, Department of Rheumatology (KU LEUVEN)
city: Brest
country: France
facility: CHRU de Brest
city: Berlin
country: Germany
facility: Deutsches Rheuma-Forschungszentrum Berlin (DRFZ)
city: Milan
country: Italy
facility: Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico (IRCCS)
city: Barcelona
country: Spain
facility: Hospital Clinic I Provicia- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofía Andaluz de Salud
city: Granada
country: Spain
facility: Hospital Universitario San Cecilio Servicio Andaluz de Salud
city: Granada
country: Spain
facility: Hospital Virgen de las Nieves Granada
city: Geneve
country: Switzerland
facility: Hospitaux Universitaires de Géneve (UNIGE)
Study officials:
affiliation: Fundación Pública Andaluza Progreso y Salud (PHFSpain)
name: Marta Alarcon
role: STUDY_DIRECTOR
References: