Identifying Unique Pathogenic Macrophages in Systemic Sclerosis-ILD

NCT ID: NCT03438032

Last Updated: 2024-11-14

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 10 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-06-28
• Study Completion Date: 2024-03-08

Brief Summary

Alveolar macrophages isolated from bronchoalveolar lavage (BAL) fluid from systemic sclerosis (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 (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.

Conditions

Fibrosis Lung; Systemic Sclerosis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

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).

Bronchoscopy with lavage

Intervention Type: DIAGNOSTIC_TEST

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

Bronchoscopy with lavage

Intervention Type: DIAGNOSTIC_TEST

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.

Interventions

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.

Intervention Type: DIAGNOSTIC_TEST

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Cara J. Gottardi

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Cara Gottardi, PhD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

Northwestern University

Chicago, Illinois, United States

Countries

United States

Other Identifiers

SP0044402

Identifier Type: -

Identifier Source: org_study_id