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

Systemic Autoimmune Diseases Clinical Trial

— PRECISESADSI  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02890134
• Other study ID #: PRECISESADS INCP (RB 15.007)
• Status: Completed
• Start date: June 2015
• Est. completion date: July 2018

Study information

• Verified date: August 2016
• Source: Andalusian Network for Design and Translation of Advanced Therapies
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 215
• Est. completion date: July 2018
• Est. primary completion date: July 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Autoimmune Diseases
• Systemic Autoimmune Diseases

Locations

Country	Name	City	State
Belgium	Université catholique de Louvain - Cliniques Universitaires Saint-Luc (UCL)	Brussels
Belgium	UZ Leuven - KU Leuven, Department of Rheumatology (KU LEUVEN)	Leuven
France	CHRU de Brest	Brest
Germany	Deutsches Rheuma-Forschungszentrum Berlin (DRFZ)	Berlin
Italy	Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico (IRCCS)	Milan
Spain	Hospital Clinic I Provicia- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)	Barcelona
Spain	Hospital Universitario Reina Sofía Andaluz de Salud	Cordoba
Spain	Hospital Universitario San Cecilio Servicio Andaluz de Salud	Granada
Spain	Hospital Virgen de las Nieves Granada	Granada
Switzerland	Hospitaux Universitaires de Géneve (UNIGE)	Geneve

Sponsors (29)

Lead Sponsor

Collaborator

Fundación Pública Andaluza Progreso y Salud

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

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Italy,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Genotyping	Genotyping will be done using a whole genome array.	2 years
Primary	Metabolite determination	Metabolite determination in plasma and urine using Nuclear Magnetic Resonance	2 years
Primary	Exosome isolation from plasma and urine	set up of the methodology for isolating exosomes in these bodily fluids for gene expression analysis	2 years
Primary	Cytokine profile determination	88 different cytokines will be assessed with Luminex	2 years
Primary	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
Primary	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