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NCT Number: NCT04917705

Search for Diagnostic and Prognostic Biomarkers in Systemic Sclerosis and Inflammatory Myopathies

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.

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Key information

Conditions

Systemic Sclerosis Connective Tissue Diseases Inflammatory Myopathies Muscular Diseases Musculoskeletal Diseases Myositis Nervous System Diseases Neuromuscular Diseases Scleroderma, Diffuse Scleroderma, Systemic Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University Hospital of Hautepierre

Strasbourg, Bas-Rhin, 67000, France

Location status: Recruiting

Location contact

Alain MEYER, MD

CONTACT

[email protected]

03 88 12 79 55 ext. +33

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Collection of biological samples

Other

Skin, muscle fiber and blood sampling

Primary outcomes

  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.

    Time frame: 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.

  2. 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.

    Time frame: 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.

  3. 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.

    Time frame: 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.

  4. 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.

    Time frame: 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.

  5. 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.

    Time frame: 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.

  6. 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.

    Time frame: 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.

  7. Comparison of the molecular profiles between systemic sclerosis and inflammatory myopathies at disease early stage.

    Time frame: 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.

  8. Comparison of the molecular profiles between systemic sclerosis and inflammatory myopathies at one year and versus disease early stage.

    Time frame: 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.

  9. Comparison of the molecular profiles between systemic sclerosis and inflammatory myopathies at 5 years and versus disease early stage.

    Time frame: 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.

Secondary outcomes

  1. Identification of molecular profiles specific to the evolution of clinical and biological characteristics of systemic sclerosis and inflammatory myopathies

    Time frame: 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)

  2. Identification of molecular profiles specific to the impact of the implementation of targeted treatments in systemic sclerosis and inflammatory myopathies

    Time frame: 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).

  3. Assessment of the presence of discriminating molecular profiles in different tissues (blood, skin, muscle) in systemic sclerosis and inflammatory myopathies

    Time frame: 5 years

    Compare the molecular profiles of blood (serum, PMBC), skin (sclerotic, healthy) and muscle, of early and advanced systemic sclerosis and inflammatory myopathies

  4. Assessment of the presence of discriminating molecular profiles in different cell subpopulations within these tissues (blood, skin, muscle) in systemic sclerosis and inflammatory myopathies

    Time frame: 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

Study contacts

Contact information is provided by the study sponsor or research team.

Alain MEYER, MD

CONTACT

[email protected]

+ 33 3 88 12 79 55

Sponsors and collaborators

Lead sponsor

University Hospital, Strasbourg, France

Other

Registry information

Official study title

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

Acronym: SCLEROMYOMICS

Important dates

Study start
2021
Primary completion
2023
Study completion
2028
First posted
Jun 8, 2021
Registry last updated
Dec 15, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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