Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Identifying Unique Pathogenic Macrophages in Systemic Sclerosis-ILD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
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

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.

Layout table for study information
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
Actual Study Start Date : June 28, 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03438032


Contacts
Layout table for location contacts
Contact: Mary Carns, MS 312-503-1137 m-carns@northwestern.edu

Locations
Layout table for location information
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Mary Carns, MS    312-503-1137    m-carns@northwestern.edu   
Principal Investigator: Anna Lam, MD         
Sponsors and Collaborators
Northwestern University
Layout table for additonal information
Responsible Party: Cara J. Gottardi, Associate Professor of Medicine, Northwestern University
ClinicalTrials.gov Identifier: NCT03438032    
Other Study ID Numbers: SP0044402
First Posted: February 19, 2018    Key Record Dates
Last Update Posted: September 6, 2019
Last Verified: September 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Scleroderma, Systemic
Scleroderma, Diffuse
Sclerosis
Pathologic Processes
Connective Tissue Diseases
Skin Diseases