Lysophosphatidic Acid / Autotaxin Axis in Rheumatoid Lung Disease

NCT04284735 | Unknown

• 2 other identifiers: 69HCL19_09302019-A03087-50
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Rheumatoid arthritis (RA) is a common chronic systemic autoimmune relapsing disease characterized by joint inflammation. Beside arthritis leading to progressive joint damage and loss of function, RA is also associated to extraarticular inflammatory conditions such as interstitial lung disease (ILD). This one develops in 30% of all RA patients with a median survival expectancy of 3 to 10 years once symptomatic. Unfortunately, there is no medical care recommendation so far as the pathophysiology is unknown. However, ILD share many similarities with idiopathic pulmonary fibrosis (IPF). Autotaxin (ATX), due to its lysophospholipase activity, produces a bioactive lipid, lysophosphatidic acid (LPA) under inflammation. LPA has pleiotropic actions inducing cell proliferation, survival, motility and differentiation. Increased ATX and LPA levels have been detected in synovial fluid of RA patients and in IPF patients. ATX is also currently the target for a phase 3 clinical trial in IPF. Given the previous described role of ATX/LPA axis in arthritis and inflammation-induced bone loss in RA and the similarities between RA-ILD and IPF, the investigators hypothesized that ATX/LPA axis may be also an attractive drug target for this pulmonary condition in RA and therefore that ATX and LPA may be increased in sputum from RA patients with ILD in comparison with sputum from RA patients without ILD.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid arthritis; Interstitial lung disease; Autotaxin; Lysophosphatidic acid

Outcome Measures

Primary Outcomes (1)

• ATX and LPA levels in sputum from RA patients with ILD in comparison with sputum from RA patients without ILD

  All the samples will be frozen and ATX and LPA levels will be assessed in the plasma and sputum at the same time, at the end of the recruitment.

  Month 30

Secondary Outcomes (1)

• Correlation between ATX and LPA levels and severity of RA-ILD estimated by tomodensitometry

  Month 24

Study Arms (2)

Controls

OTHER

Patients with RA and without ILD

Other: Quantitative ATX and LPA determination in plasma and sputum

Cases

OTHER

Patients with RA and ILD

Other: Quantitative ATX and LPA determination in plasma and sputum

Interventions

Quantitative ATX and LPA determination in plasma and sputum OTHER

Determination of ATX and LPA levels in plasma and sputum from RA-ILD patients ("cases") and in plasma and sputum from RA patients without ILD ("controls") after sputum induction using hypertonic saline inhalation

Cases; Controls

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject aged ≥ 18 and ≤ 70 years
• Patient with RA with ACPA in the state phase, meeting ACR / EULAR 2010 criteria
• For female subjects:
• Inability to procreate: menopause (absence of a rule for at least 1 year) or hysterectomy or bilateral oophorectomy or tubal ligation.
• Subject having given written consent to participate in the study
• Subject affiliated to the Social Security scheme or benefiting from an equivalent scheme
• \- PID is defined as damage compatible with the thoracic scanner in thin sections according to international criteria with or without associated clinical signs.
• \- No functional lung complaints

You may not qualify if:

• Vulnerable patient within the meaning of current French legislation (deprived of liberty by judicial or administrative decision, under guardianship or curatorship or under the protection of justice)
• Patient not fluent in French
• Woman breastfeeding or planning a pregnancy for the duration of the study
• Patient with occupational exposure to particles known to be responsible for PID (silica, etc.)
• Patient with an autoimmune disease other than RA or an auto-inflammatory disease
• \- Patient with a history of asthma, COPD or any other pulmonary pathology or pulmonary symptom unrelated to PID
• \- Patient with a history of asthma, COPD, any other pulmonary pathology, any pulmonary symptom or any pulmonary CT abnormality.

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Hôpital Lyon Sud

Pierre-Bénite, France

RECRUITING

MeSH Terms

Conditions

Arthritis, Rheumatoid; Lung Diseases, Interstitial

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Fabienne COURY-LUCAS, MD

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fabienne COURY-LUCAS, MD

CONTACT

04 78 86 56 95; fabienne.coury@chu-lyon.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2020
• First Posted: February 26, 2020
• Study Start: March 3, 2021
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2023
• Last Updated: July 27, 2021

Record last verified: 2021-07

Locations

FR (1)