Defining the Molecular and Radiologic Phenotype of Progressive RA Interstitial Lung Disease (MOUNTAIN)

Defining the Molecular and Radiologic Phenotype of Progressive RA Interstitial Lung Disease (MOUNTAIN)

A study to identify patients with Rheumatoid Arthritis - Associated Interstitial Lung Disease (RA-ILD) that are at the highest risk for progression.

The goal of the investigators is to recruit a group of patients with RA-ILD and collect information to help us understand more about disease progression. The investigators will do this using a combination of clinical, radiologic, and biologic features.

Study Overview

• Status: Recruiting
• Conditions: Rheumatoid Arthritis; Interstitial Lung Disease
• Intervention / Treatment: Genetic: Research Testing Performed (Laboratory); Diagnostic test: Information Collected as Standard of Care; Other: Research Testing Performed

Detailed Description

The central hypothesis is that novel quantitative imaging and specific blood markers will be associated with progressive RA-ILD. The hypothesis will be tested through collection and analysis of peripheral blood, in addition to the analysis of HRCT (high-resolution computed tomography) scans performed as standard of care (clinical) on research subjects.

Procedures performed:

Baseline Year 0: Blood sample, buccal (cheek) swab, questionnaires and if performed clinically - Pulmonary Function tests, 6 Minute Walk Test, and HRCT scan of lungs

Every 4 months (at clinic visit): Blood sample, questionnaires

Year 1 and Year 2 Follow-ups: Blood sample, buccal (cheek) swab, questionnaires and if performed clinically - Pulmonary Function tests, 6 Minute Walk Test, and HRCT scan of lungs

• Study Type: Observational
• Enrollment (Estimated): 450

Contacts and Locations

• Study Contact: Name: Haylie Lengel; Phone Number: 970-376-8303; Email: Haylie.Lengel@cuanschutz.edu
• Study Contact Backup: Name: Joyce S Lee; Phone Number: 303-724-6109; Email: joyce.lee@cuanschutz.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California San Francisco
      • Contact: Paul Wolters, MD
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Denver
      • Contact: Haylie A Lengel; Phone Number: 970-376-8303; Email: haylie.lengel@cuanschutz.edu
      • Principal Investigator: Joyce S Lee, MD
  • Kansas
    • Kansas City, Kansas, United States, 66103
      • Recruiting
      • University of Kansas
      • Contact: Scott Matson, MD
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
      • Contact: Justin Oldham, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

RA-ILD study patients will be recruited from the University of Colorado Hospital, ILD Clinic (CU, PI: Joyce Lee, MD), in addition to the Rheumatology Clinic at the University of Colorado Hospital. Subjects will additionally be recruited from three unaffiliated ILD centers: University of California San Francisco (UCSF; site PI Dr. Paul Wolters), University of Kansas (KU, site PI Dr. Scott Matson), and University of Michigan (UM, site PI Dr. Justin Oldham).

Description

Inclusion Criteria:

• Multidisciplinary diagnosis of RA-ILD based on the 2010 American College of Rheumatology criteria
• 18 years of age or older

Exclusion Criteria:

• Prior medication treatment specifically for RA-ILD
• Inability to give informed consent
• Pregnant women

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patients with RA-ILD; Assessments include: Clinical: height, weight, oxygen saturation at rest, and 6-minute walk test.; Rheumatological: study Rheumatologist will document rheumatoid arthritis symptoms and clinical findings at baseline and follow-up.; Pulmonary Function Testing: data will be collected from clinically performed spirometry and diffusing capacity for carbon monoxide.; High-resolution computed tomography (HRCT) imaging: HRCT scans will be collected at baseline and 12 months in line with standard of care for treatment of RA-ILD.; Lab specimens: peripheral blood will be obtained for DNA, RNA, serum, and plasma at baseline and at 12 months for all sites or every 3-4 months in Colorado. Buccal swabs (cheek) will also be collected once each year.; Information collected: will include demographics, co-morbidities, disease history, medication history, pulmonary function, radiographic imaging, and transplant/survival status through questionnaires and medical chart review.

Genetic: Research Testing Performed (Laboratory); Blood collection (DNA, RNA); Diagnostic test: Information Collected as Standard of Care; High Resolution CT Scan (Chest), Pulmonary Function Testing (PFT), 6-Minute Walk Test (6MWT); Other: Research Testing Performed; Blood collection (non-genetic), Buccal Swab, Rheumatologic Assessment, Pulmonary Assessment, Questionnaires

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluating the role of novel quantitative imaging	Through evaluation of baseline CT scans and application of novel quantitative technology, investigators will monitor for specific patterning to identify patients at risk for progression.	5-years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparing peripheral blood telomere length (PB-TL)	Investigators will test and validate if baseline peripheral blood telomere length (PB-TL) predicts a progressive phenotype in RA-ILD.	5-years
Defining peripheral blood transcriptomic profiles	Investigators will define and validate the peripheral blood transcriptomic profile of progressive RA-ILD.	5-years
Exploring if a composite profile more accurately identifies progressive RA-ILD	Investigators will use logistic least absolute shrinkage and selection operator (LASSO) to develop a predictive model of RA-ILD progression using demographics, novel imaging, PB-TL and peripheral blood transcriptome.	5-years

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); University of Michigan; University of California, San Francisco; University of Kansas
• Investigators: Principal Investigator: Joyce S Lee, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2024
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2034

Study Registration Dates

• First Submitted: December 1, 2023
• First Submitted That Met QC Criteria: April 29, 2024
• First Posted (Actual): May 3, 2024

Study Record Updates

• Last Update Posted (Actual): May 3, 2024
• Last Update Submitted That Met QC Criteria: April 29, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial
• Other Study ID Numbers: 23-0295; 1R01HL168126-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No