Imaging of Lymphatic Vessels in People With Rheumatoid Arthritis (RA)

Rheumatoid Arthritis Clinical Trial

Official title:

Near InfraRed Fluorescence Imaging of Lymphatic Transport Using Indocyanine Green: Phase II Pilot

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05197530
• Other study ID #: STUDY6830
• Secondary ID: 2R01AR056702-11A
• Status: Recruiting
• Phase: Phase 1
• Start date: December 30, 2021
• Est. completion date: June 2025

Study information

• Verified date: May 2023
• Source: University of Rochester
• Contact: Joseph Solomon, BS
• Phone: 585-275-1634
• Email: joseph_solomon[@]urmc.rochester.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Lymphatic transport was previously examined by these investigators using Near InfraRed Indocyanine Green fluorescence imaging (NIR-ICG) of the upper extremities. They established reliable and reproducible methodologies in RA patients. The purpose of this phase 2 pilot is to study RA disease progression and effectiveness as well as the mechanism of action of clinical interventions using established NIR-ICG methodologies in previous studies.

Description:

In preclinical studies, these investigators demonstrated that amelioration of tumor necrosis factor (TNF)-induced arthritis with anti-TNF, but not methotrexate (MTX) therapy, correlates with normalization of ICG clearance and popliteal lymph node (PLN) contractions. In RA patients during hand flare, it was found that ICG clearance from the web spaces, and numbers of ICG+ lymphatic basilic vessels of RA hands, are significantly decreased vs. healthy controls. Based on these observations, two important questions warrant testing to assess the clinical utility of NIR-ICG biomarkers in RA hands: Does amelioration of active synovitis pre and post treatment) correlate with: 1) increased ICG clearance (primary outcome) and/or 2) recovery of basilic ICG+ vessels (secondary outcome)? To formally address these questions, a clinical pilot will be conducted of early RA patients with symptomatic disease in their hand(s), who will undergo NIR-ICG imaging at baseline, 16-weeks, and 1-year post anti-TNF therapy, and examine if NIR-ICG outcome measures predict and correlate with clinical response.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: June 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Early RA

• Ability to provide written informed consent

• Subjects must be 18 years old or older

• RA subjects must fulfill 2010 American College of Rheumatology (ACR) criteria with a DAS28-C-Reactive Protein (CRP) >3.5

• Must have 1 year or less of disease

• Must be MTX inadequate responder (DAS28-CRP >2.6 at 4 months of therapy) OR experience a flare on MTX (self-reported and score of >25 on the Outcome Measures in Rheumatology (OMERACT) Flare questionnaire AND are starting an anti-TNF therapy.

• Must have active synovitis in one or both hands confirmed by ultrasound

Established RA

• Ability to provide written informed consent

• Subjects must be 18 years of age or older

• RA subjects must fulfill 2010 ACR criteria with a DAS-CRP >3.5

• Must have at least 10 years of disease

• Must have active synovitis in one or both hands confirmed by ultrasound

• Must be on a stable dose of DMARD (MTX, leflunomide, azulfidine, hydroxychloroquine), Janus Kinase (JAK) inhibitor or biologic agent for 8 weeks

Exclusion Criteria: All PATIENTS

• Active systemic disorders or inflammatory conditions other than RA, (i.e., chronic infections with hepatitis B, hepatitis C or HIV) that would confound the study results.

• Known sensitivity to iodine because of residual iodide in Indocyanine Green

• Pregnant women should not participate; pregnancy tests will not be performed

• Inability to donate blood due to poor venous access

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Indocyanine green
A trained physician will inject 0.1 ml of the ICG in to the web spaces of the hands in both upper extremities.

Device:
• MultiSpectral Imaging System
Once the ICG is injected, the contrast is expected to fluoresce underneath the MultiSpectral Imaging System. Multispectral video and still images will be recorded at the study visits.

Locations

Country	Name	City	State
United States	University of Rochester	Rochester	New York

Sponsors (3)

Lead Sponsor	Collaborator
University of Rochester	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clearance	The change in Indocyanine Green signal intensity (arbitrary units) over time is measured by observing the fluorescence using the Multispectral Imaging System. The MSImager software analyses the signal intensity. This outcome measure will be quantified for both early RA and late RA subjects.	1 week post injection
Secondary	Lymphatic Vessels	Using 2D still images from the NIR scanning sessions, lymphatic vessel location will be identified, and vessel numbers will be quantified. Comparisons with 2D images will be performed to identify vessel location and numbers. The images will then be superimposed upon each other in order to confirm concordance of lymphatic vessels. This outcome measure will be quantified for both early RA and late RA subjects.	16 weeks
Secondary	Contraction Rate	The contraction rate is measured as lymphatic vessel contractions/min in the dominant lymphatic vessel efferent to the injection site using the MultiSpectral Imaging System (MSImager) that captures real time movies. The MSImager software analyses the signal intensity to determine the contraction rate. This outcome measure will be quantified for both early RA and late RA subjects.	16 weeks