Imaging Lymphatic Function in Normal Subjects and in Persons With Lymphatic Disorders

Phase I/II Combinational Investigational New Drug Application: Imaging Lymphatic Function in Normal Subjects and in Persons With Lymphatic Disorders

The purpose of this study is to demonstrate the feasibility of near-infrared fluorescence imaging in subjects with acquired or hereditary lymphedema, in subjects with lipidema and other lymphovascular disorders and in normal health subjects; in order to attempt to correlate imaging phenotype(s) with genotype(s).

Study Overview

• Status: Unknown
• Conditions: Lymphedema; Dercum Disease; Lipedema; Vascular Anomaly; Vascular Malformation; Lymphatic Disorders
• Intervention / Treatment: Drug: NIRFLI with ICG

Detailed Description

Currently, there is no method to assess lymphatic function in persons with acquired (developed following surgery or trauma) lymphedema, hereditary lymphedema or other lympho-vascular disorders. The causes of these disorders, and the means to distinguish between them, is not available from existing diagnostics. A method to monitor lymphatic function could assist in the development of new therapies, the prediction of a patient's susceptibility to develop these disorders, and the evaluation of patient's conditions or responses to therapy and treatment. In this Phase I/II trial, we inject Indocyanine Green (ICG) off-label as a lymph contrast agent and use a custom designed fluorescence imager to conduct near-infrared fluorescence imaging to dynamically follow lymphatic trafficking in subjects. Blood is also collected for DNA analysis. The resulting images are analyzed, and the phenotypes observed in both normal and diseased subjects are used to correlate to mutations of specific genes reported to be associated with lymphatic development.

• Study Type: Observational
• Enrollment (Anticipated): 283

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Lymphedema Clinic at Memorial Hermann Hospital in the Texas Medical Center
    • Houston, Texas, United States, 77030
      • UT Physicians Pediatric Surgery Clinic
    • The Woodlands, Texas, United States, 77384
      • Wound Care Clinic at CHI St. Luke's The Woodland's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

1) Persons with lymphatic dysfunction (e.g. lymphedema, lipedema, dercums, etc.), 2) Persons with vascular malformation that suggest a lymphatic component, 3) Family members of persons, whom participated in this study, with a lymphatic dysfunction or vascular malformation that suggests a lymphatic component and 3) Healthy, normal individuals as controls

Description

Inclusion Criteria for Participation in NIRFLI with ICG (Group 1):

1. Negative urine pregnancy test within 36 hours prior to study drug administration, if female of childbearing potential.
2. Females must complete the Female Enrollment Form. Those subjects of childbearing potential must agree to use one of the medically accepted methods of contraception listed on the form for a period of one month following the study. Female subjects of non-childbearing potential, defined as physiologically incapable of becoming pregnant, must meet the criteria listed on the Female Enrollment form, but are not restricted to the use of contraception following study participation.
3. Subjects must be able to lie on their backs for periods of 10 minutes at at time for up to a total of 60 minutes.
4. Children must be able to remain reasonably still for the time required for imaging.
5. Subjects with lymphatic dysfunction must be diagnosed with lymphedema, lipedema, or vascular malformation/anomaly that suggests a lymphatic component.

Exclusion Criteria for Participation in NIRFLI with ICG (Group 1):

1. Persons with mobililty issues that could make participating too difficult
2. Women who are pregnant or breast-feeding
3. Persons who are allergic to iodine
4. Persons who weigh in excess of 400 lbs
5. If the subject is a female of child-bearing potential, she must agree to use a contraceptive for one month after study participation.
6. Persons who do not meet inclusion criteria.

Inclusion Criteria for Participation in Genetic Analysis Only (Group 2):

1. The subject has a family member with lymphatic dysfunction.
2. The subject is willing to have blood drawn or saliva collected for DNA analysis

Exclusion Criteria for Participation in Genetic Analysis Only (Group 2):

1) The subject has experienced a medical problem from a prior blood draw

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1: NIRFLI with ICG; 1) Persons affected with lymphatic or lympho-vascular disorders, 2) Family members (affected or unaffected) of persons affected with lymphatic or lympho-vascular disorders and 3) Health, normal persons (Controls) that participate at one of the clinical sites in both the lymphatic function imaging with indocyanine green and the Near-infrared Fluorescence Lymphatic Imaging (NIRFLI) system, as well, as the genetic analysis portion of the study.	Drug: NIRFLI with ICG; We conduct Near-infrared Fluorescence Lymphatic Imaging following the off-label use of Indocyanine Green as a lymph contrast agent and the use of a custom designed fluorescence imager to dynamically follow lymphatic trafficking in subjects. We seek to use the resulting phenotypes acquired in normal and diseased patients to correlate to mutations of specific genes reported to be associated with lymphatic development.; Other Names: ICG; IC-Green; Cardio-Green; Near-infrared Fluorescence Lymphatic Imaging (NIRFLI)
2: Genetic Analysis Only; Family members of an affected subject from Group 1. Subjects in Group 2 can be either affected or unaffected and will provide a blood or saliva sample for the genetic analysis portion of the study, but will not undergo lymphatic function imaging with ICG and the NIRFLI system. Group 2 individuals are not required to travel to one of the clinical sites in order to participate in the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Near-infrared fluorescence lymphatic imaging (NIRFLI) provides informaton on lymphatic function or dysfunction to diagnose disorders	Images are collected for up to 3 hours after injection with indocyanine green

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: National Cancer Institute (NCI); National Heart, Lung, and Blood Institute (NHLBI); Lymphatic Malformation Institute; Lipedema Foundation
• Investigators: Principal Investigator: Eva M Sevick, PhD, The University of Texas Health Science Center, Houston

Publications and helpful links

General Publications

• Rasmussen JC, Tan IC, Marshall MV, Fife CE, Sevick-Muraca EM. Lymphatic imaging in humans with near-infrared fluorescence. Curr Opin Biotechnol. 2009 Feb;20(1):74-82. doi: 10.1016/j.copbio.2009.01.009. Epub 2009 Feb 23.
• Rasmussen JC, Zvavanjanja RC, Aldrich MB, Greives MR, Sevick-Muraca EM. Near-infrared fluorescence lymphatic imaging of Klippel-Trenaunay syndrome. J Vasc Surg Venous Lymphat Disord. 2017 Jul;5(4):533-537. doi: 10.1016/j.jvsv.2017.01.011.

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (ANTICIPATED): December 1, 2019
• Study Completion (ANTICIPATED): June 1, 2020

Study Registration Dates

• First Submitted: January 30, 2009
• First Submitted That Met QC Criteria: January 30, 2009
• First Posted (ESTIMATE): February 2, 2009

Study Record Updates

• Last Update Posted (ACTUAL): May 23, 2018
• Last Update Submitted That Met QC Criteria: May 21, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Lymphedema; Genetic; Lipedema; Vascular Anomaly; Lymphatic Disorder; Vascular Malformation; Dercum Disease
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Metabolic Diseases; Skin Diseases; Connective Tissue Diseases; Lipid Metabolism Disorders; Cardiovascular Abnormalities; Lipomatosis; Lymphedema; Disease; Congenital Abnormalities; Lymphatic Diseases; Lipedema; Adiposis Dolorosa; Vascular Malformations
• Other Study ID Numbers: HSC-IMM-08-0415; R01HL092923 (NIH); R01CA128919 (NIH)