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).

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.

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