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

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Primary Purpose

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Indocyanine green

MultiSpectral Imaging System

About this trial

This is an interventional basic science trial for Rheumatoid Arthritis focused on measuring Near InfraRed, Lymphatic Transport, Imaging, Indocyanine Green, ICG, Rheumatoid Arthritis, MSImager

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University of RochesterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Early RA (<1 year of disease)

Established RA (> 10 years of disease)

Arm Description

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).

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)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

Full Information

NCT ID

NCT05197530

First Posted

January 3, 2022

Last Updated

May 10, 2023

Sponsor

University of Rochester

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT05197530

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

December 30, 2021 (Actual)

Primary Completion Date

December 2024 (Anticipated)

Study Completion Date

June 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Rochester

Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

No

Data Monitoring Committee

No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rheumatoid Arthritis

Keywords

Near InfraRed, Lymphatic Transport, Imaging, Indocyanine Green, ICG, Rheumatoid Arthritis, MSImager

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Early RA (<1 year of disease)

Arm Type

Experimental

Arm Description

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).

Arm Title

Established RA (> 10 years of disease)

Arm Type

Experimental

Arm Description

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)

Intervention Type

Drug

Intervention Name(s)

Indocyanine green

Other Intervention Name(s)

ICG, IC-Green, 1748-701-02

Intervention Description

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

Device

Intervention Name(s)

MultiSpectral Imaging System

Other Intervention Name(s)

MSImager

Intervention Description

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.

Primary Outcome Measure Information:

Title

Clearance

Description

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.

Time Frame

1 week post injection

Secondary Outcome Measure Information:

Title

Lymphatic Vessels

Description

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.

Time Frame

16 weeks

Title

Contraction Rate

Description

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.

Time Frame

16 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

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: 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Joseph Solomon, BS

Phone

585-275-1634

Email

joseph_solomon@urmc.rochester.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Christopher Ritchlin, MD, MPH

Organizational Affiliation

University of Rochester

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Rochester

City

Rochester

State/Province

New York

ZIP/Postal Code

14642

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Joseph Solomon, BS

Phone

585-275-1634

Email

joseph_solomon@urmc.rochester.edu

Rheumatoid Arthritis

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial