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

Trial Summary

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 data supports the effectiveness of the treatment Near InfraRed Indocyanine Green fluorescence imaging (NIR-ICG) for rheumatoid arthritis?

Research shows that Near InfraRed Indocyanine Green fluorescence imaging (NIR-ICG) can effectively detect joint inflammation and synovitis (inflammation of the joint lining) in rheumatoid arthritis, often performing better or comparably to traditional imaging methods like MRI. ^{1 2 3 4 5}

Is NIR-ICG imaging safe for humans?

Indocyanine green (ICG) is generally safe for use in humans, with rare adverse reactions that can include toxic or hypersensitivity responses. It is commonly used in medical imaging, such as in eye procedures, and has been studied for imaging inflammation in arthritis. ^{1 6 7 8 9}

How does NIR-ICG imaging differ from other treatments for rheumatoid arthritis?

NIR-ICG imaging is unique because it uses near-infrared fluorescence to detect joint inflammation, which can provide early diagnosis and treatment of rheumatoid arthritis without the need for traditional contrast agents or specialist interpretation, unlike many current imaging techniques. ^{1 2 3 4 6}

What is the purpose of this trial?

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.

Research Team

Christopher Ritchlin, MD, MPH

Principal Investigator

University of Rochester

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

3D-printed tissue-simulating phantoms for near-infrared fluorescence imaging of rheumatoid diseases. [2022]

2. United States 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. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Near-infrared fluorescence imaging with indocyanine green-lactosomes in a mouse model of rheumatoid arthritis. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Fluorescence-aided tomographic imaging of synovitis in the human finger. [2015]

5. Ireland 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. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Inflammation assessment in patients with arthritis using a novel in vivo fluorescence optical imaging technology. [2022]

7. United States 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. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Fluorescence optical imaging in pediatric patients with inflammatory and non-inflammatory joint diseases: a comparative study with ultrasonography. [2018]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Immediate Reactions to Fluorescein and Indocyanine Green in Retinal Angiography: Review of Literature and Proposal for Patient's Evaluation. [2022]