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Identifying Unique Pathogenic Macrophages in Systemic Sclerosis-ILD

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ClinicalTrials.gov Identifier: NCT03438032
Recruitment Status : Recruiting
First Posted : February 19, 2018
Last Update Posted : September 6, 2019
Sponsor:
Information provided by (Responsible Party):
Cara J. Gottardi, Northwestern University

Tracking Information
First Submitted Date February 12, 2018
First Posted Date February 19, 2018
Last Update Posted Date September 6, 2019
Actual Study Start Date June 28, 2018
Estimated Primary Completion Date February 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: February 15, 2018)
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
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Identifying Unique Pathogenic Macrophages in Systemic Sclerosis-ILD
Official Title Identifying Unique Pathogenic Macrophages in Systemic Sclerosis-ILD Using High Throughput Single-cell RNA-Seq
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.
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
Study Design Observational Model: Cohort
Time Perspective: Cross-Sectional
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
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.

Condition
  • Fibrosis Lung
  • Systemic Sclerosis
Intervention 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.
Study Groups/Cohorts
  • 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.
    Intervention: Diagnostic Test: Bronchoscopy with lavage
  • Control
    Healthy control subjects recruited from the Northwestern community will complete demographic and basic medical forms to ensure health
    Intervention: Diagnostic Test: Bronchoscopy with lavage
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: February 15, 2018)
20
Original Estimated Enrollment Same as current
Estimated Study Completion Date June 1, 2020
Estimated Primary Completion Date February 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Mary Carns, MS 312-503-1137 m-carns@northwestern.edu
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT03438032
Other Study ID Numbers SP0044402
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party Cara J. Gottardi, Northwestern University
Study Sponsor Northwestern University
Collaborators Not Provided
Investigators Not Provided
PRS Account Northwestern University
Verification Date September 2019