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CD73+ Th1.17 in Rheumatoid Arthritis and Psoriatic Arthritis (LAdoRIC)

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ClinicalTrials.gov Identifier: NCT03953378
Recruitment Status : Completed
First Posted : May 16, 2019
Last Update Posted : May 16, 2019
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

Brief Summary:
Prospective study to investigate the correlation between CD39/CD73 expression by the different T lymphocyte subpopulations in the blood and synovial fluid (if available) into patients with chronic inflammatory rheumatism RA and PsA types, with the rheumatic activity, the background therapy (with Methotrexate (MTX)) and the response to this treatment.

Condition or disease Intervention/treatment
Rheumatoid Arthritis Psoriatic Arthritis Other: Multi-parametric Flow Cytometry analysis on patients and healthy donors samples

Detailed Description:
Th1.17 compose a recently described subset of highly polyfunctional and thus potentially more harmful CD4+ effector T cells (Teff) than classical Th17 as they co-produce interferon-γ (IFN-γ) and interleukin-17A (IL-17A). For this reason, Th1.17 rise increasing interest in RA and PsA since they seem involved in their pathophysiology. Hyper activation of Teff in RA and PsA results partly from a deficiency in regulatory mechanisms of Teff's pro-inflammatory functions. The ecto-nucleotidase CD73 delineates Teff enriched in Th1.17 features and acts as a regulatory mechanism for these pro-inflammatory cells. Considering that MTX, usually used as first line treatment of RA and PsA, increases extracellular concentrations of adenosine monophasphate (AMP) and immunosuppressive adenosine, the investigators hypothesized that CD4+CD73+ T cell effector population enriched in Th1.17 and Th17 cells may participate in the pathogenicity of RA and PsA but also in the resistance to MTX treatment through the specific expression of CD73 essential for Ado generation and which is down-regulated on proliferating T cells.

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Study Type : Observational
Actual Enrollment : 41 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Presence and Impact of CD73+ Th1.17 and of the CD39/CD73/Adenosine Cascade in Rheumatoid Arthritis (RA) and Psoriatic Arthritis (PsA)
Actual Study Start Date : September 2016
Actual Primary Completion Date : December 2018
Actual Study Completion Date : December 2018


Group/Cohort Intervention/treatment
Group "RA patients"
Patients with Rheumatoid Arthritis (RA) fulfilling the American College of Rheumatology and European League Against Rheumatism 2009 criteria.
Other: Multi-parametric Flow Cytometry analysis on patients and healthy donors samples

Collection of venous blood (16 mL) and synovial fluid (when available) samples, for each patient, at inclusion and in the frame of the usual medical follow-up at 3 months and between 6 and 12 months, before the onset of MTX (untreated patients) or during the course of MTX treatment (MTX-treated patients).

Collection of anonymous healthy donors blood samples, age- and sex-matched, obtained from the Etablissement Français du Sang.

Multi-parametric Flow Cytometry analysis was performed on these samples to assess CD73 expression on total memory T cells and within T helper lymphocyte subsets, their cytokine production and AMPase functions. For FoxP3 intracellular staining, cells were treated using the FoxP3 Fixation and Permeabilization kit (Life Technologies), according to manufacturer instructions. Stainings were analyzed on a LSR-Fortessa™ (BD Biosciences) with conserved settings throughout the entire study and data were analyzed using FlowJo™ Software (Tree Star v10.4).


Group "PsA patients"
Patients with Psoriatic Arthritis (PsA) fulfilling the Classification for PsA (CASPAR) criteria.
Other: Multi-parametric Flow Cytometry analysis on patients and healthy donors samples

Collection of venous blood (16 mL) and synovial fluid (when available) samples, for each patient, at inclusion and in the frame of the usual medical follow-up at 3 months and between 6 and 12 months, before the onset of MTX (untreated patients) or during the course of MTX treatment (MTX-treated patients).

Collection of anonymous healthy donors blood samples, age- and sex-matched, obtained from the Etablissement Français du Sang.

Multi-parametric Flow Cytometry analysis was performed on these samples to assess CD73 expression on total memory T cells and within T helper lymphocyte subsets, their cytokine production and AMPase functions. For FoxP3 intracellular staining, cells were treated using the FoxP3 Fixation and Permeabilization kit (Life Technologies), according to manufacturer instructions. Stainings were analyzed on a LSR-Fortessa™ (BD Biosciences) with conserved settings throughout the entire study and data were analyzed using FlowJo™ Software (Tree Star v10.4).


Group "Healthy donors"
Anonymous healthy donors from the Etablissement Français du Sang.
Other: Multi-parametric Flow Cytometry analysis on patients and healthy donors samples

Collection of venous blood (16 mL) and synovial fluid (when available) samples, for each patient, at inclusion and in the frame of the usual medical follow-up at 3 months and between 6 and 12 months, before the onset of MTX (untreated patients) or during the course of MTX treatment (MTX-treated patients).

Collection of anonymous healthy donors blood samples, age- and sex-matched, obtained from the Etablissement Français du Sang.

Multi-parametric Flow Cytometry analysis was performed on these samples to assess CD73 expression on total memory T cells and within T helper lymphocyte subsets, their cytokine production and AMPase functions. For FoxP3 intracellular staining, cells were treated using the FoxP3 Fixation and Permeabilization kit (Life Technologies), according to manufacturer instructions. Stainings were analyzed on a LSR-Fortessa™ (BD Biosciences) with conserved settings throughout the entire study and data were analyzed using FlowJo™ Software (Tree Star v10.4).





Primary Outcome Measures :
  1. CD73 expression on T helper lymphocyte subpopulations [ Time Frame: At inclusion ]
    Determine CD73 expression on T helper lymphocyte subpopulations (using multi-parametric Flow Cytometry), in the blood and synovial fluid of Rheumatoid Arthritis (RA) or Psoriatic Arthritis (PsA) patients before or under MTX treatment.

  2. CD73 expression on T helper lymphocyte subpopulations [ Time Frame: 3 months ]
    Determine CD73 expression on T helper lymphocyte subpopulations (using multi-parametric Flow Cytometry), in the blood and synovial fluid of Rheumatoid Arthritis (RA) or Psoriatic Arthritis (PsA) patients before or under MTX treatment.

  3. CD73 expression on T helper lymphocyte subpopulations [ Time Frame: 12 months ]
    Determine CD73 expression on T helper lymphocyte subpopulations (using multi-parametric Flow Cytometry), in the blood and synovial fluid of Rheumatoid Arthritis (RA) or Psoriatic Arthritis (PsA) patients before or under MTX treatment.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with chronic inflammatory rheumatism RA and PsA types with or without background therapy at the inclsuion
Criteria

Inclusion Criteria:

  • Patients aged ≥ 18 years
  • Patients naive to biologics
  • Patients with RA fulfilling the American College of Rheumatology and European League Against Rheumatism 2009 criteria
  • Patients with PsA fulfilling the Classification for PsA (CASPAR) criteria

Exclusion Criteria:

  • None

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03953378


Locations
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France
Service de Rhumatologie, Centre Hospitalier Lyon-Sud (HCL)
Pierre-Bénite, France, 69495
Sponsors and Collaborators
Hospices Civils de Lyon

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Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT03953378     History of Changes
Other Study ID Numbers: LAdoRIC
First Posted: May 16, 2019    Key Record Dates
Last Update Posted: May 16, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Arthritis, Psoriatic
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Spondylarthropathies
Spondylarthritis
Spondylitis
Spinal Diseases
Bone Diseases
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases