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

NCT ID: NCT02890134

Last Updated: 2021-10-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

215 participants

Study Classification

OBSERVATIONAL

Study Start Date

2015-06-30

Study Completion Date

2018-07-31

Brief Summary

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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

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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.

Conditions

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Systemic Autoimmune Diseases

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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UCB Biopharma S.P.R.L.

INDUSTRY

Sponsor Role collaborator

Atrys Health

INDUSTRY

Sponsor Role collaborator

National Research Council, Spain

OTHER_GOV

Sponsor Role collaborator

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

OTHER

Sponsor Role collaborator

Servicio Cántabro de Salud

OTHER

Sponsor Role collaborator

August Pi Sunyer Biomedical Research Institute

OTHER

Sponsor Role collaborator

Karolinska Institutet

OTHER

Sponsor Role collaborator

KU Leuven

OTHER

Sponsor Role collaborator

Klinikum der Universität Köln

OTHER

Sponsor Role collaborator

Hannover Medical School

OTHER

Sponsor Role collaborator

Medical University of Vienna

OTHER

Sponsor Role collaborator

Quartz Bio S.A.

OTHER

Sponsor Role collaborator

Andaluz Health Service

OTHER_GOV

Sponsor Role collaborator

The Cyprus Foundation for Muscular Dystrophy Research

OTHER

Sponsor Role collaborator

Universidad de Granada

OTHER

Sponsor Role collaborator

University of Milan

OTHER

Sponsor Role collaborator

Université Catholique de Louvain

OTHER

Sponsor Role collaborator

University Hospital, Brest

OTHER

Sponsor Role collaborator

University of Geneva, Switzerland

OTHER

Sponsor Role collaborator

Szeged University

OTHER

Sponsor Role collaborator

Bayer

INDUSTRY

Sponsor Role collaborator

Institut de Recherches Internationales Servier

OTHER

Sponsor Role collaborator

Sanofi

INDUSTRY

Sponsor Role collaborator

Eli Lilly and Company

INDUSTRY

Sponsor Role collaborator

Charite University, Berlin, Germany

OTHER

Sponsor Role collaborator

Centro Hospitalar do Porto

OTHER

Sponsor Role collaborator

Institut d'Investigació Biomèdica de Bellvitge

OTHER

Sponsor Role collaborator

Innovative Medicines Initiative

OTHER

Sponsor Role collaborator

Fundación Pública Andaluza Progreso y Salud

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Marta Alarcon

Role: STUDY_DIRECTOR

Fundación Pública Andaluza Progreso y Salud (PHFSpain)

Locations

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

Brussels, , Belgium

Site Status

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

Leuven, , Belgium

Site Status

CHRU de Brest

Brest, , France

Site Status

Deutsches Rheuma-Forschungszentrum Berlin (DRFZ)

Berlin, , Germany

Site Status

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico (IRCCS)

Milan, , Italy

Site Status

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

Barcelona, , Spain

Site Status

Hospital Universitario Reina Sofía Andaluz de Salud

Córdoba, , Spain

Site Status

Hospital Universitario San Cecilio Servicio Andaluz de Salud

Granada, , Spain

Site Status

Hospital Virgen de las Nieves Granada

Granada, , Spain

Site Status

Hospitaux Universitaires de Géneve (UNIGE)

Geneva, , Switzerland

Site Status

Countries

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Belgium France Germany Italy Spain Switzerland

Other Identifiers

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PRECISESADS INCP (RB 15.007)

Identifier Type: -

Identifier Source: org_study_id