Near InfraRed Fluorescence Using Indocyanine Green and Magnetic Resonance Lymphography of Lymphatic Transport

Phase 1

Completed

• Conditions: Rheumatoid Arthritis
• Interventions: Drug: Indocyanine Green; Device: MultiSpectral Imaging System

• Registration Number: NCT04046146
• Lead Sponsor: University of Rochester

Brief Summary

Lymphatic transport will be examined using Near InfraRed Indocyanine Green fluorescence imaging (NIR-ICG) and magnetic resonance lymphography (MRL) of the upper extremities. The purpose of the study is to establish if NIR-ICG is a valid clinical outcome for quantifying lymphatic vessel drainage.

Detailed Description

Lymphedema from various etiologies (i.e. infection, cancer, surgery, and rheumatoid arthritis) remains a major health concern. Efforts to develop effective treatments for this condition have been limited by the absence of quantitative outcome measures for lymphatic function. Published articles have supported the fact that human lymphatic contractions can be readily visualized after intradermal administration of micrograms of Indocyanine Green using laser-induced fluorescence. We recently demonstrated the feasibility of NIR imaging to quantify lymphatic drainage in the hands, wrists and forearms of healthy volunteers following intradermal web space ICG injection into the hand . To establish this emerging technology as a valid clinical outcome measure, however, we must address two major questions that confound interpretation of the imaging results: 1) are the ICG filled vessels lymphatic vessels and/or small veins?; and 2) does NIR-ICG imaging following web space injection fully capture lymphatic flow from the metacarpophalangeal (MCP) joints that are most commonly involved in RA? To answer these questions, healthy patients will be recruited to have intradermal and intra-articular injections of ICG and gadolinium followed by an imaging sessions (NIR or magnetic resonance imaging) to measure lymphatic contraction rates and flow.

Study Timeline

• Study First Submitted: 2019-07-23
• Study First Submitted QC: 2019-08-02
• Study First Posted: 2019-08-06
• Study Start: 2019-12-15
• Primary Completion: 2020-03-15
• Study Completion: 2020-03-15
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-03
• Last Update Posted: 2020-09-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2

Inclusion Criteria

• Ability to provide written informed consent.
• Subjects must be 18 years old or older.

Exclusion Criteria

• Active systemic disorders or inflammatory conditions (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
• Known sensitivity to gadolinium
• Any history of kidney disease
• Pregnant women should not participate; pregnancy tests will not be performed.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
NIR-ICG MRL	MultiSpectral Imaging System	We may ask healthy subjects to return for up to four injection sessions for the study. The first injection session will consist of intradermal injection of ICG into the webspaces of the hand as done in our previous studies followed by NIR camera imaging. The second session will consist of intradermal gadolinium injection and intravenous (IV) iron contrast agent followed by MRI imaging approximately 1 week after the first session. The third session will occur at minimum eight weeks later and entail intra-articular ICG injection in order to evaluate drainage via the lymphatics. The MCP joints will be identified in the non-dominant hand and injected with ICG. Approximately one week later, the fourth session will compromise of intra-articular gadolinium injection and IV iron contrast to confirm lymphatic drainage. The MCP joints of the non-dominant hand will again be identified and injected with gadolinium.
NIR-ICG MRL	Indocyanine Green	We may ask healthy subjects to return for up to four injection sessions for the study. The first injection session will consist of intradermal injection of ICG into the webspaces of the hand as done in our previous studies followed by NIR camera imaging. The second session will consist of intradermal gadolinium injection and intravenous (IV) iron contrast agent followed by MRI imaging approximately 1 week after the first session. The third session will occur at minimum eight weeks later and entail intra-articular ICG injection in order to evaluate drainage via the lymphatics. The MCP joints will be identified in the non-dominant hand and injected with ICG. Approximately one week later, the fourth session will compromise of intra-articular gadolinium injection and IV iron contrast to confirm lymphatic drainage. The MCP joints of the non-dominant hand will again be identified and injected with gadolinium.

Primary Outcome Measures

Name	Time	Method
Lymphatic contraction rate measured via NIR ICG camera. Unit of measure: # contraction/minute	12 months	Images collected from NIR scanning sessions will be analyzed to determine lymphatic contraction rate by identifying number of contractions per minute.
Manual lymphatic vessel counts via assessment of 2D images of NIR-ICG compared to MRI. Unit of measure: # lymphatic vessels/hand	12 months	Vessel location and numbers will be identified using 2D still images from the NIR scanning sessions and with 2D MR images. These images will be superimposed upon each other in order to confirm concordance of lymphatic vessels. Number of lymphatic vessels in the hands will be manually counted.
ICG clearance measured from hand using NIR ICG images. Unit of measure: (% difference Visit 1 from Visit 2)	12 months	2D still images collected from NIR scanning sessions will be analyzed to determine ICG clearance by comparing the % difference from visit 1 to visit 2.

Trial Locations

Locations (1)

University of Rochester; 🇺🇸 Rochester, New York, United States