Near InfraRed Fluorescence Using Indocyanine Green and Magnetic Resonance Lymphography of Lymphatic Transport (NIR-ICG MRL)

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Indocyanine Green; Device: MultiSpectral Imaging System

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 Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 89 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: NIR-ICG MRL; 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.

Drug: Indocyanine Green; A trained physician will inject 0.1 ml of Indocyanine Green into the web spaces of the hands in both upper extremities. Subjects may have up to five study visits to confirm feasibility, safety, and reproducibility.; Other Names: ICG; IC-Green; 17478-701-02; Device: MultiSpectral Imaging System; Once the Indocyanine Green 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
Manual lymphatic vessel counts via assessment of 2D images of NIR-ICG compared to MRI. Unit of measure: # lymphatic vessels/hand	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.	12 months
Lymphatic contraction rate measured via NIR ICG camera. Unit of measure: # contraction/minute	Images collected from NIR scanning sessions will be analyzed to determine lymphatic contraction rate by identifying number of contractions per minute.	12 months
ICG clearance measured from hand using NIR ICG images. Unit of measure: (% difference Visit 1 from Visit 2)	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.	12 months

Collaborators and Investigators

• Sponsor: University of Rochester
• Investigators: Principal Investigator: Homaira Rahimi, MD, MTR, University of Rochester

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 15, 2019
• Primary Completion (ACTUAL): March 15, 2020
• Study Completion (ACTUAL): March 15, 2020

Study Registration Dates

• First Submitted: July 23, 2019
• First Submitted That Met QC Criteria: August 2, 2019
• First Posted (ACTUAL): August 6, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 4, 2020
• Last Update Submitted That Met QC Criteria: September 3, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Imaging; Healthy Volunteers; ICG; Gadolinium; GAD; Indocyanine Green; NIR; Lymphatic Transport; NIR-ICG; rhuematoid arthritis
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Arthritis
• Other Study ID Numbers: STUDY3891

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Information of any type may be shared with researchers at other institutions. Subjects will be made aware of this in the informed consent form.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No