- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03438032
Identifying Unique Pathogenic Macrophages in Systemic Sclerosis-ILD
Identifying Unique Pathogenic Macrophages in Systemic Sclerosis-ILD Using High Throughput Single-cell RNA-Seq
Study Overview
Status
Conditions
Intervention / Treatment
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 (ACR) 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 fluorescence-activated cell sorter (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
Enrollment (Actual)
Contacts and Locations
Study Locations
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Illinois
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Chicago, Illinois, United States, 60611
- Northwestern University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Subjects with SSc-ILD will be recruited from the Northwestern University Scleroderma Program.
Healthy control subjects recruited from the Northwestern community.
Description
Inclusion Criteria:
- meet 2013 ACR criteria for diagnosis of SSc
- have radiographic evidence for ILD and a forced vital capacity <70% on PFT
- have not taken immune suppression in the last 2 months OR have taken a stable dose of mycophenolate mofetil, rituximab, or prednisone less than or equal to 10 mg for at least 6 months
Exclusion Criteria:
- diagnosis of an overlap syndrome, such as lupus or rheumatoid arthritis
- unable to provide informed consent in English
- currently pregnant or nursing
- current smoker or former smoker (greater than 10 pack years)
- leukopenia
- anemia
- comorbidities of uncontrolled congestive heart failure, cancer not in remission, HIV, or chronic liver disease
- known or suspected infection in the past 3 months
- BMI greater than or equal to 30 kg/m2
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
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 pulmonary function test (PFT).
|
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
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Single-cell RNA-seq analysis
Time Frame: Baseline and 6 months
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Change in alveolar macrophage transcriptome at 6 months, as measured by single cell RNA-sequencing
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Baseline and 6 months
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- SP0044402
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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