ILD-SARDs Registry and Biorepository

NCT ID: NCT05007340

Last Updated: 2021-09-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Total Enrollment

252 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-08-24

Study Completion Date

2026-08-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

A complex interaction between demographic, environmental and genetic mechanisms impact the onset, severity and outcome of ILD-SARDs through dysregulation of the immune system and lung pro-biotic pathways. Comorbidity and genetic risk indicate that there are overlapping pathogenic mechanisms among SARDs, some of which underlie ILD in different SARDs.

The purpose of this biobank is to study the clinical, pathological, laboratory, and imaging characteristics of SARDs patients with lung involvement. This will help identify as unique features underlying lung involvement in SARDs. In addition, this may lead to the discovery of novel mechanisms of disease and potentially novel targets of treatment for SARDs patients with lung disease.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

1\. BACKGROUND AND STUDY RATIONALE: Characterized by immune dysregulation with disrupted self-tolerance, systemic autoimmune rheumatic diseases (SARDs) result in inflammation and auto-antibody formation that cause multi-tissue damage. The prototypic SARDs are rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and autoimmune myositis (AIM). The lung is a frequent target of autoimmune-mediated injury in patients with SARDs, and interstitial lung disease (ILD) is a major cause of morbidity and mortality in patients with SARDs. Among patients with SARDs, ILD varies widely in terms of its morphological pattern, time course, severity and the specific immune cells and cytokines that are most responsible for lung damage.

Fundamental clinical questions remain unanswered for understanding diagnosis and management of ILD-SARDs:

1. ILD-SARDs prediction: Which patients with SARDs are likely to develop ILD? In retrospective cohorts of patients with RA, a patient's risk of developing ILD can be predicted by their age, sex and presence of auto-antibodies. How these clinical features interact with possible genetic and environmental risk factors needs to be better established to identify SARDs patients most at risk of developing ILD and to design and test interventions that reduce that risk or delay the onset of clinical manifestations in high-risk patients.
2. ILD-SARDs pathogenesis in humans and preclinical models: Why is there considerable heterogeneity in ILD progression and severity in patients with ILD-SARDs? The fundamental changes that occur in the immune system and lungs of patients with ILD-SARDs are still poorly understood. This is in part due to a lack of appropriate pre-clinical models of ILD-SARDs and lung biopsies from patients with ILD-SARDs. Identifying the biologic processes that promote development of ILD in SARDs patients will let the Investigators use drugs for other ILDs to specific patients with ILD-SARDs and promote the development of new targeted therapies.
3. ILD-SARDs treatment: Which are the best therapies for patients with ILD-SARDs? Few proven treatments for patients with ILD-SARDs exist. Many are proposed based only on case reports in specific SARDs. Positive results from studies of anti-fibrotic agents patients show it is possible to reverse the fibrotic process; yet it is unclear whether some patients with ILD-SARDs could also benefit from this approach as it may interact with the immunosuppressive agents the participants already receive. Addressing this issue is critical to changing the natural course of ILD-SARDs, particularly the symptoms and outcomes most important to patients.

The conduct of many of the related future studies will require access to genetic material, fresh peripheral blood cells, serum and tissue from a phenotypically well characterized group of patients with ILD-SARDs. Access to patients is required for future clinical research projects and participation in potential clinical trials. Furthermore, the ILD-SARDs Registry and Biorepository is similar to registries and biorepositories that have been developed or are being developed in Germany, Australia, the United States and elsewhere in Canada. These similarities will facilitate national and international collaboration and allow establishment of a global collaborative network that is essential for further advancement of ILD-SARDs.

The aforementioned future studies that will benefit from the contributions of this Bank include the identification of cell types, immune modulators and genetic pathways dysregulated in ILD-SARDs patients; pre-clinical in vivo and ex vivo models to assess disease pathobiology and targeted interventions, such as mouse models to assess mechanisms in the initiation and progression of ILD in SARDs, as well as a human ILD-SARDs lung-on-a-chip model to assess and predict treatment effect by evaluation mechanical evolution of the tissue; the ILD-SARDs Patient Preferences study, which consists of the facilitation of focus groups to characterize ILD-SARDs patients' experiences, needs and preferences; and the existing open-label, single arm pilot study of the safety and tolerability of nintedanib in patients with ILD and autoimmune inflammatory myopathy, to assess the effect of nintedanib on the state of activation of AIM patients' blood cells and to define its effect on the immunophenotype of circulating blood cells in patients.

2\. OBJECTIVES, HYPOTHESIS AND STUDY QUESTIONS A complex interplay between demographic, environmental and genetic mechanisms impact the onset, severity and outcome of ILD-SARDs through dysregulation of the immune system and lung pro-biotic pathways. Co-morbidity and extensive sharing of genetic risk indicate that there are overlapping pathogenic mechanisms among SARDs, some of which underlie ILD in different SARDs. The multidisciplinary team will examine this hypothesis through the establishment of a prospective registry of patients with ILD-SARDs to be enrolled and followed longitudinally, combined with a biorepository.

3\. STUDY METHODS The Investigators will develop a longitudinal clinical registry and biorepository of ILD-SARDs patients. Patient recruitment, informed consent, management, storage of data/samples and all other research activities will be done in accordance with the ILD-SARDs Biobank Management Framework. The ILD-SARDs informed consent forms will be used to obtain participant consent. To estimate recruitment in this cohort, the Investigators reviewed the number of patients seen in the multispecialty ILD-SARDs clinic at the McGill University Health Centre (MUHC) over the last year. The Investigators will recruit an inception cohort for biobanking with annual collection of structured clinical data. Clinical data - including clinical rheumatologic and pulmonary assessment, serology, pulmonary function tests, CT imaging, pathology, current treatments - will be collected at every visit. A biorepository will store biological specimens such as blood cells, serum and DNA/RNA for the cohort members. More specifically, the Investigators will collect whole blood samples at visits as defined above. Those belonging to treatment-naive patients will be sent to Dr. David Langlais' lab at the Inflammation Genomics Lab of the McGill University Genome Centre for single cell RNA sequencing and immunophenotyping. A Standard Operating Process (SOP) for blood sampling, shipping and storage has been developed to detail this process. As for whole blood samples coming from non-treatment-naive-patients, those will be sent to Dr. Gregory Fonseca's lab at the Meakins-Christie Lab at the Royal Victoria Hospital to be processed, and the resulting serum will be biobanked. Moreover, patients with an available bronchoalveolar lavage, lung, skin or muscle biopsy, as well as blood samples will be asked for consent for the study staff to access those samples for the purpose of this research. These samples are essential for the mechanisms established in future studies and will help enable them. The PIs, working under different disciplines, will all equally contribute to the study by identifying eligible participants, having medical oversight and study conduct, having written confirmation of inclusion/exclusion criteria, conducting a physical exam, assessing and signing adverse events (AEs) and serious adverse events (SAEs), providing medical care and follow-up to the participant and reviewing, interpreting and signing lab and other test results. Together, this will allow for a larger number of participants to be identified and followed up in this study.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Interstitial Lung Disease Systemic Autoimmune Disease Rheumatic Diseases Rheumatic Arthritis Systemic Sclerosis Autoimmune Myositis Systemic Lupus Erythematosus Usual Interstitial Pneumonia Nonspecific Interstitial Pneumonia

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Blood draws

Blood draws will be performed by personnel that are both qualified and authorized by their employer/institution to perform the procedures. The procedures will be performed with standards expected in the context of clinical care. 40 mL (2-3 tbsp) of blood will be drawn in order to collect DNA, RNA, serum and PBMCs. Blood tubes will be sent to the Bank as per the SOP for patient blood sampling and processing. The blood will be processed, centrifuged and stored by a trained laboratory technician.

Intervention Type OTHER

Other biological samples to biobank (skin, lung and muscle biopsies; bronchoalveolar lavage (BAL fluid)

If the patient's medical care or their participation in a research project involves a biopsy or surgery to remove tissue, the tissue not required for diagnosis (excess tissue) or hospital archives will be included in the biobank. This may include healthy tissue as well as tissue affected by the patient's health condition. The Investigators will not conduct extra procedures in order to obtain samples for the sole purpose of this study and will only operate on what's available. These may include blood samples, skin, lung and muscle biopsies, and bronchoalveolar lavage, all of which will be obtained from the pathology department.

Intervention Type OTHER

Clinical data collection

Participant's relevant medical information from medical records, general health questionnaires and clinical assessments. The data includes gender, date of birth, race/ethnicity, habits, height, weight, vital signs, medical history, family history, pregnancy history, imaging data pertinent to ILDs and SARDs, results of routine blood tests, environmental exposures, medication and treatment exposures and adherence, function and quality of life, patient's assessment of their own health, clinical symptoms.

Intervention Type OTHER

Genetic data/DNA/RNA

Results of the DNA or RNA sequencing, conducted for the Biobank and will be made available to future research; possible single nucleotide polymorphism (SNP) assays (including single SNP, low-plex or microarray-based assays).

Intervention Type OTHER

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Must be aged 18 years or older
2. Diagnosis of ILD as confirmed by a chest CT
3. Either a defined SARD, an undifferentiated connective tissue disease or features of autoimmunity without meeting clinical criteria for SARD
4. Patient must be willing to give their informed consent and must be able to understand and follow the required study procedures.

Exclusion Criteria

N/A
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

McGill University

OTHER

Sponsor Role collaborator

McGill University Health Centre/Research Institute of the McGill University Health Centre

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Deborah Assayag

Principal Investigator, MD, MAS

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Christian Pineau, MD

Role: PRINCIPAL_INVESTIGATOR

McGill University Health Centre/Research Institute of the McGill University Health Centre

Inés Colmegna, MD

Role: PRINCIPAL_INVESTIGATOR

McGill University Health Centre/Research Institute of the McGill University Health Centre

Silvia Vidal, PhD

Role: PRINCIPAL_INVESTIGATOR

McGill University/Research Institute of the McGill University Health Centre

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

RI-MUHC

Montreal, Quebec, Canada

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Canada

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Deborah Assayag, MD, MAS

Role: CONTACT

514-934-1934 ext. 43882

Victoria Nam-Amnath, RN, BScN

Role: CONTACT

514-934-1934 ext. 44831

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Deborah Assayag, MD, MAS

Role: primary

514-934-1934 ext. 43882

Victoria Nam-Amnath, RN, BScN

Role: backup

514-934-1934 ext. 44831

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2021-7678

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.