Standardization of Indocyanine Green Lymphography Protocol With Exercise for Lymphedema Assessment
Phase: PHASE4
Conditions: Lymphedema
Sponsor: University of Iowa

NCT Number: NCT03584633 
Official Title: Standardization of Indocyanine Green Lymphography Protocol With Exercise for 
Lymphedema Assessment 
Document date: December 24, 2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Exercise-Enhanced ICG Lymphography 
TRIAL STATISTICIAN Evelyn Qin 
Protocol Version (SAP associated with) 
TRIAL PRINCIPAL INVESTIGATOR: Wei Chen 
SAP AUTHOR(s) Evelyn Qin, Wei Chen 
 
Abbreviations and definitions 
Indocyanine Green ICG 
SD Standard deviation 
SPSS Statistical package for the social sciences 
 
Background: 
Indocyanine green (ICG) lymphography is a non-radioactive, fluorophore-based imaging 
modality that provides functional imaging of the lymphatic system. With specificity comparable 
to and sensitivity superior to technetium99-based lymphoscintigraphy, the conventional 
diagnostic gold standard, ICG lymphography has been increasingly relied upon to 
diagnose extremity lymphedema. The diagnosis of lymphedema is confirmed when the 
pathologic dermal backflow patterns are seen. In addition to providing a definitive diagnosis, 
the 
types/distribution of the dermal backflow patterns presently allows the determination of 
disease 
severity. Since the dermal backflow patterns emerge in a delayed fashion 
and, after their initial emergence, they continually evolve until reaching a steady-state, or 
plateau, a delayed scan at the time of plateau is necessary to achieve an accurate 
representation 
of the disease. Exercise has been shown to accelerate lymphatic drainage. 
Study Objectives: 
To determine if controlled exercise could shorten the time it takes for ICG lymphography to 
reach a plateau, and to create a standardized protocol to increase the efficiency and reliability 
of 
ICG lymphography to diagnose extremity lymphedema. 
Study Methods: 
Design: non-randomized controlled trial 
Recruitment: 
All lymphedema patients presented to our lymphedema reconstruction center over a 6-month. 
period and those who met inclusion criteria were recruited into the study. 
Inclusion criteria: 18 years or older, having voluntarily agreed to participate in the study, and 
being suspected to have lymphedema or previously diagnosed with lymphedema. 
Exclusion criteria: allergy to iodine, women who were pregnant or nursing, having 
heart/lung/joint conditions that would prevent exercising. 
 
Exercise protocol: 
 
Patients presented for a one time visit. Following standard ICG injections, patients were 

exercised on a recumbent cross-trainer at five-minute intervals at specific, controlled intensity. 
Delayed scanning was performed following each exercise interval, and sequential changes of 
lymphographic patterns were recorded. The cycle of exercise/scan continued until achieving a 
plateau, or when no further lymphographic changes were observed for two consecutive cycles. 
Following the point of the plateau, further delayed scanning was performed every hour to 
identify the time point when the lymphographic patterns started to recede. Twenty-three limbs 
in 
9 patients (10 arms, 13 legs) with unilateral and bilateral lymphedema were studied. Campisi 
criteria were used to clinically stage disease severity. 
 
Statistical analysis (SAP version: 2.0) 
 
All patients who participated in the study were included in the analysis and the analysis 
compared the individuals’ affected limbs to the unaffected limbs. Video footage of indocyanine 
green lymphography was independently reviewed by three experienced ICG lymphographers to 
identify time points of ICG plateau and regression. 
SPSS was used to perform the data analysis using a significance level of 0.05 and a confidence 
interval of 95%. Descriptive analysis generated frequencies of the study variables, 
and comparisons of categorical variables were performed using the chi-square test.