Clinical trial NCT00833599: Imaging Lymphatic Function in Normal Subjects and in Persons With Lymphatic Disorders
Official title: Phase I/II Combinational Investigational New Drug Application: Imaging Lymphatic Function in Normal Subjects and in Persons With Lymphatic Disorders
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Lymphedema
Lymphatic Disorders
Lipedema
Vascular Malformation
Vascular Anomaly
Dercum Disease
Keywords: Lymphedema
Genetic
Lymphatic Disorder
Lipedema
Vascular Malformation
Vascular Anomaly
Dercum Disease
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: National Cancer Institute (NCI)
name: Lymphatic Malformation Institute
name: Lipedema Foundation
First posted: 2009-02-02
Enrollment: 283
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
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

Brief summary: 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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Near-infrared fluorescence lymphatic imaging (NIRFLI) provides informaton on lymphatic function or dysfunction to diagnose disorders
timeFrame: Images are collected for up to 3 hours after injection with indocyanine green
Secondary outcomes:
Other outcomes:
Locations:
city: Houston
country: United States
facility: Lymphedema Clinic at Memorial Hermann Hospital in the Texas Medical Center
state: Texas
city: Houston
country: United States
facility: UT Physicians Pediatric Surgery Clinic
state: Texas
city: The Woodlands
country: United States
facility: Wound Care Clinic at CHI St. Luke's The Woodland's Hospital
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: Eva M Sevick, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.