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

June 13, 2022 updated by: University of Colorado, Denver
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The Specific Aims of This Study Are As Follows:

  1. Identify whether sputum anti-CCP predicts incident RA
  2. Determine the effect of inflammatory cytokines on the induction of NETosis in sputum neutrophils
  3. Determine the role of sputum macrophage phagocytosis in NET clearance
    The knowledge gained from this study will improve the overall understanding of the development of RA. It is anticipated that these findings will improve the field's understanding of how best to screen for RA risk and target RA prevention. This study could support future lung-targeted prevention strategies for RA that could avoid the administration of systemic toxic therapies. Such potential prevention interventions could be implemented in subjects at risk for RA in order to prevent the irreversible joint damage that can occur in the later stages of clinically-apparent RA.

Study Type

Observational

Enrollment (Anticipated)

340

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University of Colorado Denver (Anschutz Medical Campus)
        • Contact:
        • Contact:
        • Principal Investigator:
          • Kristen Demoruelle, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

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.

Description

Inclusion Criteria:

  • 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:

  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

Healthy Controls :

  1. No history of RA
  2. No FDRs with RA
  3. No systemic use of immunosuppressants for autoimmune disease

RA Diagnosis:

  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)

Exclusion Criteria:

  1. Currently pregnant or planning to become pregnant during the sample collection period of the study
  2. Exacerbation of underlying obstructive lung disease within the past 1 month
  3. Known FEV1 <1 liter
  4. Oxygen requirement >2 liters at rest
  5. Participants with health acuity or behavioral health concerns leaving them unable to participate in the current research

Note: If a subject temporarily does not meet inclusion criteria but is interested in participating, he/she may participate once inclusion criteria have been met.

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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)
Observational study, no intervention will be administered.
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)
Observational study, no intervention will be administered.
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)
Observational study, no intervention will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sputum anti-CCP antibodies predicting incident RA
Time Frame: 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.
*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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effect of inflammatory cytokines on the induction of NETosis in sputum neutrophils
Time Frame: 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
*Determine the 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
Time Frame: 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
*Determine the role of sputum macrophage phagocytosis in NET clearance among At-Risk, healthy, & RA subjects
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Colorado, Denver

Collaborators

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Institutes of Health (NIH)

Investigators

  • Principal Investigator: Kristen Demoruelle, MD, PhD, University of Colorado, Denver

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2020

Primary Completion (Anticipated)

July 14, 2025

Study Completion (Anticipated)

July 14, 2025

Study Registration Dates

First Submitted

June 29, 2020

First Submitted That Met QC Criteria

July 15, 2020

First Posted (Actual)

July 16, 2020

Study Record Updates

Last Update Posted (Actual)

June 14, 2022

Last Update Submitted That Met QC Criteria

June 13, 2022

Last Verified

June 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20-0206
  • 1R01AR076450-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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