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

Recruiting

• Conditions: Rheumatoid Arthritis
• Interventions: Other: N/A (Observational Study)

• Registration Number: NCT04474392
• Lead Sponsor: University of Colorado, Denver

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.

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 \<br\> 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 Timeline

• Study First Submitted: 2020-06-29
• Study First Submitted QC: 2020-07-15
• Study First Posted: 2020-07-16
• Study Start: 2020-08-01
• Status Verified: 2022-06
• Last Update Submitted: 2022-06-13
• Last Update Posted: 2022-06-14
• Primary Completion: 2025-07-14
• Study Completion: 2025-07-14

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 340

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)

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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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Healthy Controls (N=120)	N/A (Observational Study)	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
At-Risk (N=180)	N/A (Observational Study)	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
RA Diagnosis (N=40)	N/A (Observational Study)	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

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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	\*Determine the effect of inflammatory cytokines on the induction of NETosis in sputum neutrophils
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	\*Determine the role of sputum macrophage phagocytosis in NET clearance among At-Risk, healthy, \& RA subjects

Trial Locations

Locations (1)

University of Colorado Denver (Anschutz Medical Campus); 🇺🇸 Aurora, Colorado, United States