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

NCT ID: NCT05197530

Last Updated: 2025-03-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-30
• Study Completion Date: 2025-12-31

Brief 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.

Detailed 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.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Early RA (<1 year of disease)

In this single center study, early RA subjects (\<1 year of disease) who are MTX inadequate responders or experience a flare (see inclusion criteria for detail) on MTX and are starting an anti-TNF therapy will be invited to participate to receive ICG injections at Baseline (prior to the start of medication), week 16 and week 52. NIR-ICG imaging will be done immediately post injection and 1 week later for a total of three injection/imaging visits and three imaging visits without injections. See schedule of events for more detail. Total length of participation will be up to 53 weeks (+3days).

Group Type: EXPERIMENTAL

Indocyanine green

Intervention Type: DRUG

A trained physician will inject 0.1 ml of the ICG in to the web spaces of the hands in both upper extremities.

MultiSpectral Imaging System

Intervention Type: DEVICE

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.

Established RA (> 10 years of disease)

Patients with symptomatic established RA (\>10 years) will be invited to participate in an ICG injections followed by NIR-ICG imaging and NIR-ICG imaging visit 1 week later. Total length of participation will be up to 1 week (+3 days)

Group Type: EXPERIMENTAL

Indocyanine green

Intervention Type: DRUG

A trained physician will inject 0.1 ml of the ICG in to the web spaces of the hands in both upper extremities.

MultiSpectral Imaging System

Intervention Type: DEVICE

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DEVICE

Other Intervention Names

ICG; IC-Green; 1748-701-02; MSImager

Eligibility Criteria

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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role: collaborator

University of Rochester

OTHER

Sponsor Role: lead

Responsible Party

Christopher Ritchlin

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christopher Ritchlin, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of Rochester

Locations

University of Rochester

Rochester, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Joseph Solomon, BS

Role: CONTACT

joseph_solomon@urmc.rochester.edu

585-275-1634

Facility Contacts

Joseph Solomon, BS

Role: primary

joseph_solomon@urmc.rochester.edu

585-275-1634

Other Identifiers

2R01AR056702-11A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY6830

Identifier Type: -

Identifier Source: org_study_id