NIR-ICG Imaging for Rheumatoid Arthritis

Overseen By Joseph Solomon, BS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Rochester

Must be taking: DMARDs, JAK inhibitors

Disqualifiers: Chronic infections, Iodine sensitivity, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to track rheumatoid arthritis (RA) progression and treatment response using a special imaging technique. It employs a dye called indocyanine green (also known as IC-Green, Cardio-Green, or Foxgreen) and a multispectral imaging system to monitor the disease and treatment effects within the body. Individuals with RA who have had the disease for less than a year and do not respond well to certain medications, or those with RA for over ten years with active symptoms, may qualify. The trial aims to understand how RA progresses and how treatments work over time. As a Phase 1 trial, the research focuses on understanding how the treatment functions in people, offering participants a chance to be among the first to experience this innovative approach.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications. However, if you have established RA, you must be on a stable dose of certain medications for at least 8 weeks before joining.

What prior data suggests that this imaging technique is safe for rheumatoid arthritis patients?

Research shows that indocyanine green (ICG), a dye used in medical imaging, is generally safe. The FDA approved this dye, and it has been used for over 30 years in tests related to heart and liver functions. Although side effects can occur, they are rare. Some individuals might experience allergic reactions or other negative responses, but these are uncommon.

Studies using Near InfraRed Indocyanine Green (NIR-ICG) imaging have found it to be a safe method for viewing the lymphatic system, especially in patients with rheumatoid arthritis (RA). This imaging technique uses ICG to visualize the movement of substances through the lymphatic vessels, which are part of the immune system.

Overall, both the dye and the imaging method have been well-tolerated in past uses. Prospective participants should consult a healthcare provider to understand any personal risks. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about NIR-ICG imaging for rheumatoid arthritis because it offers a new way to visualize joint inflammation using a special dye called indocyanine green combined with multispectral imaging. Unlike traditional treatments that primarily focus on reducing symptoms through drugs like methotrexate or anti-TNF therapies, this technique aims to provide a clearer, more detailed view of the disease activity in real time. This could lead to more precise monitoring of the condition, helping doctors tailor treatments more effectively to each patient’s needs. By enhancing diagnostic capabilities, this method has the potential to improve treatment outcomes and patient care significantly.

What evidence suggests that NIR-ICG imaging is effective for studying rheumatoid arthritis?

Research has shown that Near InfraRed Indocyanine Green fluorescence imaging (NIR-ICG) effectively detects joint inflammation and synovitis, the swelling of the joint lining, in people with rheumatoid arthritis (RA). This trial will use NIR-ICG imaging to assess participants with early and established RA. This method provides a clear view of affected areas by highlighting changes in blood flow caused by inflammation. Studies indicate that indocyanine green (ICG), used in this imaging, helps track treatment effectiveness for RA patients. It has been found toxic to certain cells contributing to joint inflammation in RA. These findings suggest that NIR-ICG imaging could be a promising tool for monitoring RA progression and treatment response. ^{3 4 6 7 8}

Who Is on the Research Team?

Christopher Ritchlin, MD, MPH

Principal Investigator

University of Rochester

Are You a Good Fit for This Trial?

This trial is for adults with early or established Rheumatoid Arthritis (RA) who meet specific criteria, including being on a stable dose of certain RA medications. They must have active joint inflammation in their hands confirmed by ultrasound and not be pregnant or have other systemic disorders that could affect the study.

Inclusion Criteria

Established RA: Ability to provide written informed consent

I have early RA, didn't respond well to MTX, or it flared up, and I'm starting anti-TNF therapy.

I have been diagnosed with rheumatoid arthritis and my disease activity is high.

Exclusion Criteria

I do not have chronic infections like hepatitis B, C, or HIV that could affect the study.

All Patients: Inability to donate blood due to poor venous access

All Patients: Known sensitivity to iodine because of residual iodide in Indocyanine Green

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Imaging

Participants receive ICG injections and undergo NIR-ICG imaging at baseline prior to the start of anti-TNF therapy

1 week

1 visit (in-person)

Treatment and Imaging

Participants receive anti-TNF therapy and undergo NIR-ICG imaging at 16 weeks and 1 year post-treatment

52 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Indocyanine green
• MultiSpectral Imaging System

Trial Overview The trial is testing how well Indocyanine Green, used with a MultiSpectral Imaging System, can track lymphatic vessel function in RA patients. It aims to understand disease progression and response to treatments using imaging techniques developed in earlier research.

How Is the Trial Designed?

Group I: Established RA (> 10 years of disease) Experimental Treatment 2 Interventions

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 II: Early RA (<1 year of disease) Experimental Treatment 2 Interventions

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).

Who Is Running the Clinical Trial?

University of Rochester

Lead Sponsor

Trials

883

Recruited

555,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

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

Collaborator

Trials

508

Recruited

1,090,000+

Published Research Related to This Trial

Indocyanine green (ICG)-enhanced fluorescence optical imaging (FOI) demonstrated a sensitivity of 76% and a specificity of 54% for detecting inflammation in arthritis patients, making it a promising imaging technique compared to traditional methods.

FOI showed higher sensitivity than clinical examination and good agreement with ultrasonography and MRI, indicating it can effectively detect inflammatory changes in arthritis, particularly synovitis and tenosynovitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inflammation assessment in patients with arthritis using a novel in vivo fluorescence optical imaging technology. Werner, SG., Langer, HE., Ohrndorf, S., et al.[2022]

The ICG-enhanced optical imaging system demonstrated a sensitivity of only 39.6% for detecting synovitis compared to contrast-enhanced MRI, indicating it may miss many cases of inflammation, especially mild synovitis.

However, the optical imaging system showed a higher specificity of 85.2%, meaning when it did indicate synovitis, it was often correct, particularly in cases of severe inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of synovitis in the hands of patients with rheumatologic disorders: diagnostic performance of optical imaging in comparison with magnetic resonance imaging. Meier, R., Thürmel, K., Moog, P., et al.[2022]

Adverse reactions to fluorescein and indocyanine green (ICG) during retinal angiography are rare but can include toxic, hypersensitivity, and non-specific reactions, making it important for ophthalmologists to be aware of these potential risks.

The review provides guidance for ophthalmologists to identify patients at higher risk for hypersensitivity reactions and suggests that allergy studies may benefit those with suspected sensitivities before undergoing angiography.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immediate Reactions to Fluorescein and Indocyanine Green in Retinal Angiography: Review of Literature and Proposal for Patient's Evaluation. Meira, J., Marques, ML., Falcão-Reis, F., et al.[2022]

A new 3D printing technique has been developed to create stable, anatomically accurate hand and finger models that mimic the fluorescence properties of indocyanine green (ICG), which is important for imaging in rheumatoid diseases.

Phantoms made with the fluorescent dye Lumogen IR 765 demonstrated excellent photostability for up to 4 years, significantly outperforming ICG-based phantoms that degraded over time, making them ideal for long-term imaging applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

3D-printed tissue-simulating phantoms for near-infrared fluorescence imaging of rheumatoid diseases. Schädel-Ebner, S., Hirsch, O., Gladytz, T., et al.[2022]

Indocyanine green-enhanced fluorescence optical imaging (FOI) demonstrated an 86% sensitivity and 63% specificity for detecting inflammation in early arthritis when compared to MRI, indicating it can be a useful diagnostic tool.

The study suggests that FOI may effectively monitor disease activity in clinical settings, but further multicenter studies are needed to confirm its reliability and sensitivity in detecting inflammatory changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indocyanine green-enhanced fluorescence optical imaging in patients with early and very early arthritis: a comparative study with magnetic resonance imaging. Werner, SG., Langer, HE., Schott, P., et al.[2022]

Near-infrared (NIR) fluorescence imaging using ICG-lactosomes can effectively detect joint inflammation in a mouse model of rheumatoid arthritis, showing higher fluorescence in arthritic joints compared to normal ones.

Unlike ICG alone, which quickly cleared from the body, ICG-lactosomes remained in the system for at least 48 hours and specifically accumulated in inflamed joints, suggesting a potential mechanism for targeted imaging of arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Near-infrared fluorescence imaging with indocyanine green-lactosomes in a mouse model of rheumatoid arthritis. Onishi, S., Sakane, M., Tsukanishi, T., et al.[2022]

Indocyanine green (ICG)-enhanced fluorescence molecular tomography (FMT) successfully detected synovitis in all examined arthritic finger joints of six patients with rheumatoid arthritis, showing a strong correlation with 3-T magnetic resonance imaging (MRI) results.

FMT provided a quantitative measure of synovial hyperperfusion, effectively differentiating between arthritic and healthy joints, with significant differences in scores (P < .001), indicating its potential as a reliable imaging technique for assessing joint inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluorescence-aided tomographic imaging of synovitis in the human finger. Mohajerani, P., Koch, M., Thürmel, K., et al.[2015]

Indocyanin green (ICG)-enhanced fluorescence optical imaging (FOI) demonstrated moderate sensitivity (67.3%-75.2%) and specificity (58.8%-94.3%) for detecting inflammation in juvenile idiopathic arthritis (JIA) patients compared to ultrasonography, making it a promising tool for diagnosing joint pain.

FOI was more effective than ultrasonography in identifying clinically active joints, suggesting it could serve as a valuable additional diagnostic method in pediatric rheumatology, despite both methods having limitations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluorescence optical imaging in pediatric patients with inflammatory and non-inflammatory joint diseases: a comparative study with ultrasonography. Beck, MC., Glimm, AM., Ohrndorf, S., et al.[2018]

Indocyanine Green (ICG) enhanced fluorescence optical imaging (FOI) showed lower sensitivity (57.3%) compared to magnetic resonance imaging (MRI) (89.2%) in detecting synovitis in patients with rheumatoid arthritis, indicating that MRI is more effective for this purpose.

The sensitivity of FOI improved with higher grades of synovitis, reaching 65.0% for moderate and severe cases, but it struggled with mild and moderate synovitis, highlighting its limitations in detecting less severe inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluorescence optical imaging and 3T-MRI for detection of synovitis in patients with rheumatoid arthritis in comparison to a composite standard of reference. Thuermel, K., Neumann, J., Jungmann, PM., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9123785/

Monitoring of patients with rheumatoid arthritis by indocyanine ... The aim of this study was to investigate FOI's ability to monitor the treatment response to TNFα inhibitor therapy with certolizumab pegol (CZP) in RA patients ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0301562917302983

Efficacy of Indocyanine Green-Mediated Sonodynamic ... ICG-mediated SDT is cytotoxic to fibroblast-like synoviocytes and is a potential modality for targeted therapy of synovitis in rheumatoid arthritis.

3. arthritis-research.biomedcentral.com arthritis-research.biomedcentral.com/articles/10.1186/s13075-022-02795-w/tables/2

Monitoring of patients with rheumatoid arthritis by indocyanine ... Table 2 Summary statistics of clinical and laboratory outcome parameters at baseline and after w6, w12, w24 and w52 ; Baseline. 28. 4.61 (2.65–6.49, 1.76) ; w6.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9331249/

Features Found in Indocyanine Green-Based ... Indocyanine green (ICG)-based FOI allows visualization of impaired microcirculation caused by inflammation in both hands in one examination.

5. trials.arthritis.org trials.arthritis.org/trials/NCT05197530

Imaging of Lymphatic Vessels in People with Rheumatoid ... 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 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2921028/

ICG-enhanced imaging of arthritis with an integrated ... ... Indocyanine Green (ICG), an FDA-approved fluorescent dye, could provide early detection of rheumatoid arthritis. The purpose of this study was to ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/8127574/

Adverse reactions due to indocyanine green Although adverse reactions to indocyanine green (ICG) are known to occur, the dye has been used for more than 30 years in tests of cardiac and hepatic function.

8. mdpi.com mdpi.com/2075-4418/12/8/1775

Features Found in Indocyanine Green-Based ... Indocyanine green (ICG)-based FOI allows visualization of impaired microcirculation caused by inflammation in both hands in one examination.