Identifying Unique Pathogenic Macrophages in Systemic Sclerosis-ILD

Systemic Sclerosis Clinical Trial

Official title:

Identifying Unique Pathogenic Macrophages in Systemic Sclerosis-ILD Using High Throughput Single-cell RNA-Seq

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03438032
• Other study ID #: SP0044402
• Status: Completed
• Start date: June 28, 2018
• Est. completion date: March 8, 2024

Study information

• Verified date: March 2024
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: March 8, 2024
• Est. primary completion date: October 12, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Fibrosis Lung
• Pulmonary Fibrosis
• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• 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.

Locations

Country	Name	City	State
United States	Northwestern University	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Northwestern University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Single-cell RNA-seq analysis	Change in alveolar macrophage transcriptome at 6 months, as measured by single cell RNA-sequencing	Baseline and 6 months