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Search for Diagnostic and Prognostic Biomarkers in Systemic Sclerosis and Inflammatory Myopathies (SCLEROMYOMICS)

14. desember 2021 oppdatert av: University Hospital, Strasbourg, France

Search for Diagnostic and Prognostic Biomarkers (Molecular Signatures) in Systemic Sclerosis and Inflammatory Myopathies by a Multi-OMIC Strategy Integrating a Single Cell Analysis Approach

Systemic sclerosis and inflammatory myopathies, which sometimes combine (scleromyositis), have shared pathophysiological elements. In both diseases, many cell subtypes are involved in damage to organs such as T lymphocytes, B lymphocytes, and unconventional (non-B, non-T) lymphocytes called innate lymphoid cell (ILC). The increasing complexity of our understanding of the immune system (multiplication of recognized cell subtypes) also makes the strategies for analyzing pathophysiological mechanisms more complex. Currently, no biomarker perfectly predicts the phenotype and evolution of patients. Multi-OMIC analyzes will be performed (identification of cell populations as well as genomic, transcriptomic and proteomic characterization) in blood and tissue samples (skin and muscle biopsy) in patients with systemic sclerosis and inflammatory myopathies, with the objective of identifying discriminating molecular signatures (biomarkers) according to the characteristics of the disease and its evolution.

Studieoversikt

Status

Rekruttering

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

Cohort study, monocentric, comparative, non-randomized, open-label, prospective and longitudinal, quasi-experimental.

Participating subjects will be classified according to their clinical, biological and additional investigations into one of the 4 populations presented in the eligibility criteria.

A 1st sampling point will be carried out at inclusion visit (baseline). Prospective follow-up of participating patients will be carried out as part of their routine care (1 to 2 visits per year or more if disease complications appear).

During the 5-year follow-up, the investigating physician will remain attentive to the appearance of a new clinical element which will mark the course of the disease.

During the follow-up, 2 more sampling points will be carried out (blood and / or skin) on each participating patient.

Blood samples and muscle biopsies will be carried out in the usual way during diagnostic and therapeutic management. An additional volume of blood, an additional muscle biopsy (on the occasion of the one performed for diagnosis) and two superficial skin biopsies (1 sclerotic tissue & 1 healthy tissue) will be taken for research purposes.

Inclusion in this cohort will not change the management of the patient, either with regard to his treatment or his follow-up.

Multi-omics analyzes will include single cell RNAseq, as well as proteomics and genomics analysis:

  • Transcriptomic analysis will be performed on PMBC, muscle and skin.
  • Genomic analysis (exome & whole genome) will be performed on PMBC, muscle and skin.
  • Proteomic analysis will be performed on serum, PMBC, muscle and skin.
  • Single cell analysis will be performed on PMBC, muscle and skin. During the analysis, the clinical characteristics of baseline, the treatments and the evolutions during the follow-up will be compared to reveal the clinical relevance of the multi-OMIC signatures.

Studietype

Intervensjonell

Registrering (Forventet)

55

Fase

  • Ikke aktuelt

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studiesteder

  • Frankrike
    • Bas-Rhin
      • Strasbourg, Bas-Rhin, Frankrike, 67000
        • Rekruttering
        • University Hospital of Hautepierre
        • Ta kontakt med:

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  • Control population without inflammatory myopathy (population 1), suspected myopathy for whom a blood test and muscle biopsy are required to confirm the diagnosis
  • Confirmed inflammatory myopathy (population 2)
  • Control population without systemic sclerosis (population 3), with primary Raynaud's phenomenon
  • Early diffuse systemic cutaneous scleroderma (population 4)
  • Male or female (age ≥ 18, no upper age limit)

Exclusion Criteria:

Populations 1 & 2

  • Contraindication to muscle biopsy
  • Diagnosed for another neuromuscular disease
  • Taking an immunosuppressant / immunomodulator treatment within 3 months before inclusion
  • Unbalanced cardiovascular pathology

Population 3 & 4

  • Contraindication to skin biopsy
  • Capillaroscopic and / or immunological anomaly suggesting scleroderma
  • Suspicion of scleroderma but diagnosed for another connectivitis
  • Immunosuppressive treatment (corticosteroids> 15 mg, methotrexate, mycophenolate mofetil) introduced for more than 1 month
  • Active or recent cancer <3 years (apart from non-melanoma skin cancer).

For all

- Pregnancy or breast feeding

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Grunnvitenskap
  • Tildeling: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Evolution of the molecular profiles (i.e., genomic [New Generation Sequencing], transcriptomic [RNA chip], proteomic [mass spectrometry] and identification of cell population [single cell RNA sequencing]) of systemic sclerosis during 5 years.
Tidsramme: At Day 1

This study is descriptive (non-analytical), without prior hypothesis. Molecular profiles will be assessed by integration of multi-OMIC tools from a wide range of areas of biochemistry, chemistry, physics, computing science and molecular biology.

During the 5-year follow-up, the investigating physician will remain attentive to the appearance of a new clinical element which will mark the course of the systemic sclerosis.
At Day 1
Evolution of the molecular profiles (i.e., genomic [New Generation Sequencing], transcriptomic [RNA chip], proteomic [mass spectrometry] and identification of cell population [single cell RNA sequencing]) of systemic sclerosis during 5 years.
Tidsramme: At 12 months

This study is descriptive (non-analytical), without prior hypothesis. Molecular profiles will be assessed by integration of multi-OMIC tools from a wide range of areas of biochemistry, chemistry, physics, computing science and molecular biology.

During the 5-year follow-up, the investigating physician will remain attentive to the appearance of a new clinical element which will mark the course of the systemic sclerosis.
At 12 months
Evolution of the molecular profiles (i.e., genomic [New Generation Sequencing], transcriptomic [RNA chip], proteomic [mass spectrometry] and identification of cell population [single cell RNA sequencing]) of systemic sclerosis during 5 years.
Tidsramme: 5 years

This study is descriptive (non-analytical), without prior hypothesis. Molecular profiles will be assessed by integration of multi-OMIC tools from a wide range of areas of biochemistry, chemistry, physics, computing science and molecular biology.

During the 5-year follow-up, the investigating physician will remain attentive to the appearance of a new clinical element which will mark the course of the systemic sclerosis.
5 years
Evolution of the molecular profiles (i.e., genomic [New Generation Sequencing], transcriptomic [RNA chip], proteomic [mass spectrometry] and identification of cell population [single cell RNA sequencing]) of inflammatory myopathies during 5 years.
Tidsramme: At Day 1

This study is descriptive (non-analytical), without prior hypothesis. Molecular profiles will be assessed by integration of multi-OMIC tools from a wide range of areas of biochemistry, chemistry, physics, computing science and molecular biology.

During the 5-year follow-up, the investigating physician will remain attentive to the appearance of a new clinical element which will mark the course of the inflammatory myopathies.
At Day 1
Evolution of the molecular profiles (i.e., genomic [New Generation Sequencing], transcriptomic [RNA chip], proteomic [mass spectrometry] and identification of cell population [single cell RNA sequencing]) of inflammatory myopathies during 5 years.
Tidsramme: At 12 months

This study is descriptive (non-analytical), without prior hypothesis. Molecular profiles will be assessed by integration of multi-OMIC tools from a wide range of areas of biochemistry, chemistry, physics, computing science and molecular biology.

During the 5-year follow-up, the investigating physician will remain attentive to the appearance of a new clinical element which will mark the course of the inflammatory myopathies.
At 12 months
Evolution of the molecular profiles (i.e., genomic [New Generation Sequencing], transcriptomic [RNA chip], proteomic [mass spectrometry] and identification of cell population [single cell RNA sequencing]) of inflammatory myopathies during 5 years.
Tidsramme: 5 years

This study is descriptive (non-analytical), without prior hypothesis. Molecular profiles will be assessed by integration of multi-OMIC tools from a wide range of areas of biochemistry, chemistry, physics, computing science and molecular biology.

During the 5-year follow-up, the investigating physician will remain attentive to the appearance of a new clinical element which will mark the course of the inflammatory myopathies.
5 years
Comparison of the molecular profiles between systemic sclerosis and inflammatory myopathies at disease early stage.
Tidsramme: Day 1
Comparison of the molecular profiles (i.e., genomic [New Generation Sequencing], transcriptomic [RNA chip], proteomic [mass spectrometry] and identification of cell population [single cell RNA sequencing] between systemic sclerosis and inflammatory myopathies at disease early stage.
Day 1
Comparison of the molecular profiles between systemic sclerosis and inflammatory myopathies at one year and versus disease early stage.
Tidsramme: At 12 months
Comparison of the molecular profiles (i.e., genomic [New Generation Sequencing], transcriptomic [RNA chip], proteomic [mass spectrometry] and identification of cell population [single cell RNA sequencing] between systemic sclerosis and inflammatory myopathies at one year and versus disease early stage.
At 12 months
Comparison of the molecular profiles between systemic sclerosis and inflammatory myopathies at 5 years and versus disease early stage.
Tidsramme: At 5 years
Comparison of the molecular profiles (i.e., genomic [New Generation Sequencing], transcriptomic [RNA chip], proteomic [mass spectrometry] and identification of cell population [single cell RNA sequencing] between systemic sclerosis and inflammatory myopathies at 5 years and versus disease early stage.
At 5 years

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Identification of molecular profiles specific to the evolution of clinical and biological characteristics of systemic sclerosis and inflammatory myopathies
Tidsramme: 5 years
Study of the molecular profile (i.e., genomic [New Generation Sequencing], transcriptomic [RNA chip], proteomic [mass spectrometry] and identification of cell population [single cell RNA sequencing]) of systemic sclerosis during a systemic or infectious complication (initial profile compared to the profile at the time of the complication)
5 years
Identification of molecular profiles specific to the impact of the implementation of targeted treatments in systemic sclerosis and inflammatory myopathies
Tidsramme: 5 years
Study of the molecular profile (i.e., genomic [New Generation Sequencing], transcriptomic [RNA chip], proteomic [mass spectrometry] and identification of cell population [single cell RNA sequencing]) of systemic sclerosis before and after the implementation of targeted treatments (immunomodulators, cell therapies).
5 years
Assessment of the presence of discriminating molecular profiles in different tissues (blood, skin, muscle) in systemic sclerosis and inflammatory myopathies
Tidsramme: 5 years
Compare the molecular profiles of blood (serum, PMBC), skin (sclerotic, healthy) and muscle, of early and advanced systemic sclerosis and inflammatory myopathies
5 years
Assessment of the presence of discriminating molecular profiles in different cell subpopulations within these tissues (blood, skin, muscle) in systemic sclerosis and inflammatory myopathies
Tidsramme: 5 years
Compare the molecular profiles in different cell subpopulations within blood, skin and muscle tissues by single cell analysis in systemic sclerosis and inflammatory myopathies
5 years

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

University Hospital, Strasbourg, France

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

25. november 2021

Primær fullføring (Forventet)

1. juni 2023

Studiet fullført (Forventet)

1. juni 2028

Datoer for studieregistrering

Først innsendt

22. april 2021

Først innsendt som oppfylte QC-kriteriene

1. juni 2021

Først lagt ut (Faktiske)

8. juni 2021

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

15. desember 2021

Siste oppdatering sendt inn som oppfylte QC-kriteriene

14. desember 2021

Sist bekreftet

1. desember 2021

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • 8181

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

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