Clinical trial NCT02890147: Molecular Reclassification to Find Clinically Useful Biomarkers for Systemic Autoimmune Diseases: Case-control
Official title: Molecular Reclassification to Find Clinically Useful Biomarkers for Systemic Autoimmune Diseases: Case-control
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Healthy Subjects
Keywords: SADs
Healthy Volunteers
Molecular profiles
Omics Techniques
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: 649
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Healthy Volunteers

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 constitute a Healthy Volunteers cohort to compare with systemic autoimmune diseases cohort into molecular clusters instead of clinical entities through the determination of molecular profiles using several "Omics" techniques.

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.

Eligibility criteria: Inclusion Criteria:

* Aged 18 years or older at the time of consent
* Signed the informed consent form

Exclusion Criteria:

* Individuals on chronic medication.
* Individuals suffering from any inflammatory, autoimmune, allergic or infectious condition and if possible without a history of autoimmune disease, particularly thyroid disease or other diseases that may modify cellular profiles in blood.
* Pregnant women.

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 expression methylation in total blood
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna
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: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Szeged
country: Hungary
facility: University of Szeged
city: Milan
country: Italy
facility: Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico (IRCCS)
city: Milan
country: Italy
facility: UNIMI, Istituto Ortopedico Getano Pini
city: Porto
country: Portugal
facility: Centro Hospitalar do Porto
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: Biobanco del Sistema Sanitario Público de Andalucía (SSPA)
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: Malaga
country: Spain
facility: Hospital Regional de Málaga Servicio Andaluz de Salud
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla, Servicio Cántabro de Salud
city: Geneve
country: Switzerland
facility: Hospitaux Universitaires de Géneve
Study officials:
affiliation: Fundación Pública Andaluza Progreso y Salud (PHFSpain)
name: Marta Alarcon
role: STUDY_DIRECTOR
References: