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

May 10, 2023 updated by: Christopher Ritchlin, University of Rochester

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 1

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 Locations

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

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

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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).
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.
Other Names:
  • ICG
  • IC-Green
  • 1748-701-02
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.
Other Names:
  • MSImager
Experimental: 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)
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.
Other Names:
  • ICG
  • IC-Green
  • 1748-701-02
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.
Other Names:
  • MSImager

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clearance
Time Frame: 1 week post injection
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Lymphatic Vessels
Time Frame: 16 weeks
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
Contraction Rate
Time Frame: 16 weeks
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

Collaborators and Investigators

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

Sponsor

University of Rochester

Collaborators

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

Investigators

  • Principal Investigator: Christopher Ritchlin, MD, MPH, University of Rochester

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)

December 30, 2021

Primary Completion (Anticipated)

December 1, 2024

Study Completion (Anticipated)

June 1, 2025

Study Registration Dates

First Submitted

January 3, 2022

First Submitted That Met QC Criteria

January 3, 2022

First Posted (Actual)

January 19, 2022

Study Record Updates

Last Update Posted (Actual)

May 12, 2023

Last Update Submitted That Met QC Criteria

May 10, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY6830
  • 2R01AR056702-11A1 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

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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