Sputum Studies of Anti-Citrullinated Protein Antibodies (ACPA) and Rheumatoid Arthritis (RA) Origins

NCT04474392 | Unknown

• 2 other identifiers: 20-02061R01AR076450-01
• Study Type: observational
• Target: 340
• Locations: 1 country
• Sites: 1

Brief Summary

The study is designed to learn more about the causes of rheumatoid arthritis (RA). People who get RA have elevated protein markers called autoantibodies in their blood years before initial symptoms of arthritis. The goal of this study is to learn more about how autoantibodies in RA might be related to inflammation in the lungs.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Sputum anti-CCP antibodies predicting incident RA

  \*Sputum anti-CCP antibodies every year for 3 years (subjects At-Risk for RA); to identify whether sputum anti-CCP predicts incident RA

  1-3 years per participant (depending on group); study visits x1 per year, with option for 3 additional visits over 1 year for a subgroup of participants.

Secondary Outcomes (2)

• Effect of inflammatory cytokines on the induction of NETosis in sputum neutrophils

  1-3 yrs / participant; At-Risk Group: Baseline Visit & 2 Follow-up Annual Visits (w/ potential to have 3 additional visits in 1 year); Healthy Controls & RA Diagnosed: Baseline Visit & 1 Follow-up Visit, approximately 1 year later

• The role of sputum macrophage phagocytosis in NET clearance

  1-3 years / participant; At-Risk Group: Baseline Visit & 2 Follow-up Annual Visits (w/ potential to have 3 additional visits in 1 year); Healthy Controls & RA Diagnosed: Baseline Visit & 1 Follow-up Visit, approximately 1 year later

Study Arms (3)

At-Risk (N=180)

1. No evidence of inflammatory arthritis on clinical examination AND 2. At elevated risk for RA based on familial or serologic risk * Familial risk includes having a first degree relatives (FDRs) with RA * Serologic risk includes asymptomatic serum ACPA positivity There will be 1 study visit per year for 3 years; for a subset of 30 of these participants, there will be an additional 3 quarterly visits in one year. Study Procedures (Baseline \& Follow-up): * Questionnaires * Physical and joint exam * Measurement of participants' height, weight * Blood and sputum collection

Other: N/A (Observational Study)

Healthy Controls (N=120)

1. No history of RA 2. No FDRs with RA 3. No systemic use of immunosuppressants for autoimmune disease Participants will return for 1 follow-up visit, approximately 1 year after their baseline visit. Study Procedures (Baseline \& Follow-up): * Questionnaires * Physical and joint exam * Measurement of participants' height, weight * Blood and sputum collection

Other: N/A (Observational Study)

RA Diagnosis (N=40)

1. Classified RA by 1987 ACR and/or 2010 ACR/EULAR RA classification criteria (confirmed by medical chart review) OR 2. Diagnosed with RA by a board-certified rheumatologist (confirmed by medical chart review) Participants will return for 1 follow-up visit, approximately 1 year after their baseline visit. Study Procedures (Baseline \& Follow-up): * Questionnaires * Physical and joint exam * Measurement of participants' height, weight * Blood and sputum collection

Other: N/A (Observational Study)

Interventions

N/A (Observational Study) OTHER

Observational study, no intervention will be administered.

At-Risk (N=180); Healthy Controls (N=120); RA Diagnosis (N=40)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

We will recruit subjects from 1) the Denver site of the SERA project (COMIRB #01-0675); 2) local rheumatology clinics, including the University of Colorado Hospital (UCH), Denver Health, National Jewish Health (NJH), and the Denver Arthritis Clinic; 3) local health clinics at UCH; and 4) local advertisements.

You may qualify if:

• Adults between 18 and 100 years;
• At-Risk for RA, RA diagnosed, and Healthy Control subjects will be included in the study until recruitment goals are met for each group.
• At-Risk:
• No evidence of inflammatory arthritis on clinical examination AND
• At elevated risk for RA based on familial or serologic risk
• Familial risk includes having a first degree relatives (FDRs) with RA
• Serologic risk includes asymptomatic serum ACPA positivity
• Healthy Controls :
• No history of RA
• No FDRs with RA
• No systemic use of immunosuppressants for autoimmune disease
• RA Diagnosis:
• Classified RA by 1987 ACR and/or 2010 ACR/EULAR RA classification criteria (confirmed by medical chart review) OR
• Diagnosed with RA by a board-certified rheumatologist (confirmed by medical chart review)

You may not qualify if:

• Currently pregnant or planning to become pregnant during the sample collection period of the study
• Exacerbation of underlying obstructive lung disease within the past 1 month
• Known FEV1 \<1 liter
• Oxygen requirement \>2 liters at rest
• Participants with health acuity or behavioral health concerns leaving them unable to participate in the current research
• If interested, please take a few minutes to complete the screening questionnaire for this study opportunity. You may open the survey in your web browser by clicking the link below:
• https://is.gd/SPAROscreen
• If the link above does not work, try copying the link below into your web browser:
• https://redcap.ucdenver.edu/surveys/?s=3WM8WH3WKK

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Institutes of Health (NIH): collaborator
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator

Study Sites (1)

University of Colorado Denver (Anschutz Medical Campus)

Aurora, Colorado, 80045, United States

RECRUITING

Related Publications (61)

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Biospecimen

Retention: SAMPLES WITH DNA

Blood, saliva, and sputum samples are collected for this study. The blood, saliva, and sputum samples are stored in -80 freezers at the Barbara Davis Center.

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Observation

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Study Officials

• Kristen Demoruelle, MD, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kasey Bales

CONTACT

303-724-0071; KASEY.BALES@CUANSCHUTZ.EDU

Kristin Sturm, MA

CONTACT

303-724-5658; KRISTIN.STURM@CUANSCHUTZ.EDU

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2020
• First Posted: July 16, 2020
• Study Start: August 1, 2020
• Primary Completion: July 14, 2025
• Study Completion: July 14, 2025
• Last Updated: June 14, 2022

Record last verified: 2022-06

Locations

US (1)