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Trial record 5 of 9 for:    Interstitial | Recruiting, Not yet recruiting, Available Studies | "Scleroderma, Systemic"

Identifying Unique Pathogenic Macrophages in Systemic Sclerosis-ILD

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ClinicalTrials.gov Identifier: NCT03438032
Recruitment Status : Not yet recruiting
First Posted : February 19, 2018
Last Update Posted : April 5, 2018
Sponsor:
Information provided by (Responsible Party):
Northwestern University

Brief Summary:
Alveolar macrophages isolated from bronchoalveolar lavage (BAL) fluid from SSc patients with clinically significant lung fibrosis will be studied at baseline and at 6 months after enrollment to assess longitudinally the presence and persistence of an emergent, pro-fibrotic alveolar macrophage population, using single cell RNA-Seq technology to measure the individual transcriptome from each cell.

Condition or disease Intervention/treatment
Fibrosis Lung Systemic Sclerosis Diagnostic Test: Bronchoscopy with lavage

Detailed Description:

Using cutting-edge single cell RNA-Seq technology, we will identify in the BAL fluid of subjects of SSc-ILD emerging pathogenic cell populations in the lung that were previously unrecognized using standard RNA-Seq and microarray technologies, which lack the resolution to analyze transcriptomes of individual cells. Alveolar macrophages isolated from bronchoalveolar lavage (BAL) fluid from SSc patients with clinically significant lung fibrosis will be studied at baseline and at 6 months after enrollment to assess longitudinally the presence and persistence of an emergent, pro-fibrotic alveolar macrophage population.

Subjects with SSc-ILD will be recruited from the Scleroderma Program. We will recruit adults who fulfill 2013 American College of Rheumatology SSc criteria and clinically relevant SSc-interstitial lung disease. Patients will undergo bronchoscopy with bronchoalveolar lavage at month 0 and then at month 6. Healthy control subjects will complete demographic and basic medical forms to ensure health. Pertinent clinical data will be downloaded from the Enterprise Data Warehouse, an electronic database in use at Northwestern that was designed to aggregate and store patient data from various medical systems, or through manual chart review, and entered into a RedCap database created specifically for this project.

During an elective bronchoscopy procedure in SSc and healthy control subjects the bronchoscope will be wedged into an affected lung segment guided by CT scanning. After wedging the bronchoscope, 120ml of sterile 0.09% normal saline will be instilled. All subsequent aliquots will be pooled. Up to 40-60 mL of BAL fluid will be obtained for analysis during each sampling. Alveolar macrophages will be sorted on a FACS Aria III instrument. High-throughput single cell transcriptomic (Drop-seq) data will be processed on Northwestern high-performance computational cluster using Cell Ranger pipeline and post-processed using modified AltAnalyze pipeline.


Study Type : Observational
Estimated Enrollment : 20 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Identifying Unique Pathogenic Macrophages in Systemic Sclerosis-ILD Using High Throughput Single-cell RNA-Seq
Estimated Study Start Date : May 1, 2018
Estimated Primary Completion Date : February 1, 2020
Estimated Study Completion Date : June 1, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Scleroderma

Group/Cohort Intervention/treatment
SSc-ILD
SSc-ILD subjects will be defined by those who fulfill 2013 American College of Rheumatology SSc criteria and have forearm modified Rodnan skin scores/mRSS ≥1 (a validated, semi-quantitative scoring system for dermal fibrosis) and clinically relevant SSc-interstitial lung disease (ILD). A subject will be defined as having ILD if they have radiographic evidence for ILD and a forced vital capacity <70% on PFT.
Diagnostic Test: Bronchoscopy with lavage
During an elective bronchoscopy procedure, the bronchoscope will be wedged into an affected lung segment guided by CT scanning. When involved an anterior segment will be used to maximize return. After wedging the bronchoscope, 120ml of sterile 0.09% normal saline will be instilled. Up to 40-60 mL of BAL fluid will be obtained for analysis during each sampling.

Control
Healthy control subjects recruited from the Northwestern community will complete demographic and basic medical forms to ensure health
Diagnostic Test: Bronchoscopy with lavage
During an elective bronchoscopy procedure, the bronchoscope will be wedged into an affected lung segment guided by CT scanning. When involved an anterior segment will be used to maximize return. After wedging the bronchoscope, 120ml of sterile 0.09% normal saline will be instilled. Up to 40-60 mL of BAL fluid will be obtained for analysis during each sampling.




Primary Outcome Measures :
  1. Single-cell RNA-seq analysis [ Time Frame: Baseline and 6 months ]
    Change in alveolar macrophage transcriptome at 6 months, as measured by single cell RNA-sequencing



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

Subjects with SSc-ILD will be recruited from the Northwestern University Scleroderma Program.

Healthy control subjects recruited from the Northwestern community.

Criteria

Inclusion Criteria:

  • forearm modified Rodnan skin scores/mRSS ≥1
  • have radiographic evidence for ILD and a forced vital capacity <70% on PFT

Exclusion Criteria:

-patients currently taking immunosuppression (methotrexate, IVIg, cyclophosphamide, etc.) in the preceding 2 months will be excluded.


Responsible Party: Northwestern University
ClinicalTrials.gov Identifier: NCT03438032     History of Changes
Other Study ID Numbers: SP0044402
First Posted: February 19, 2018    Key Record Dates
Last Update Posted: April 5, 2018
Last Verified: April 2018

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

Additional relevant MeSH terms:
Sclerosis
Scleroderma, Systemic
Scleroderma, Diffuse
Pulmonary Fibrosis
Pathologic Processes
Connective Tissue Diseases
Skin Diseases
Lung Diseases
Respiratory Tract Diseases