Clinical trial NCT03584633
Conditions: Lymphedema
Keywords: Indocyanine Green Indocyanine Green Lymphography Exercise
Sponsor: University of Iowa
Start date: 2019-04-15; Completion date: 2019-12-31
Enrollment: 9 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Indocyanine Green (ICG) lymphography is a relatively new imaging technique that allows for quick visualization of superficial lymph flow in real-time, without radiation exposure. This imaging is useful for diagnosing and assessing lymphedema. ICG lymphography has a higher sensitivity and specificity than lymphoscintigraphy, the current gold standard imaging device for lymphedema. ICG lymphography precisely and reliably diagnoses, tracks, and stages lymphedema severity, ranging from subclinical or early lymphedema to more advanced cases. The ICG contrast dye used to visualize the lymphatic system takes approximately six hours to plateau. Therefore, patients must wait six hours between their initial and delayed scans.

The purpose of this study is to determine if exercising on a Nu-step device between ICG initial and delayed scans would shorten the period of time a patient had to spend at the hospital on the day of their ICG lymphography.

The general procedures for this involve (after selecting subjects, consenting subjects, educating the subject on the protocol, along with other appropriate measures):

* Taking baseline vitals (HR \& SpO2) and limb circumference measurements
* 5-minute period of time to acquaint subject with the exercise equipment (Nu-Step) at any level of exertion
* injection of contrast agent to allow for visualization of the superficial lymphatic system by a qualified nurse
* Initial scan
* A 5-minute period of exercise at "moderate" level of exercise (This correlates to the rating of perceived exertion levels of 12-13; All exercise periods should be at this level and will be monitored by a provider)
* Second scan \& vitals
* 5-minute period of exercise
* Third scan \& vitals

  o Continue 5-minute exercise period followed by scan \& vitals until disease pattern emerges

  \* Exercise for 5 minutes then scan and vitals until images reach steady state for two consecutive scans
* Final vitals (HR \& SpO2)

  \* Repeat scan every 1 hour until the normal 6 hour scan to monitor for further changes in lymphatic pattern.
* Exit survey

Detailed description:
Following consent, the patients will answer the questions in the screening questionnaire and this data will be collected. Patients that do not screen out of the study (i.e. meet all inclusion criteria and none of the exclusion criteria) will continue with the study. Individuals who meet the exclusion criteria will not continue.

Study participants will be asked to go to the Rehabilitation Therapies clinic on the lower level of the main hospital for a one time visit. The visit will take approximately three to six hours.

During the visit, height and weight will be measured. Circumference measurements of the arms and legs will also be measured with a measuring tape. Bioimpedance analysis of the limb will be performed to assess the fluid content in the limbs.

Pain Ease numbing spray will have been applied to three injection sites on the affected arm or leg. 0.1ml of 0.25% Indocyanine green (ICG) dye will then be injected into the distal arm or leg at three separate sites: two interdigital injections and one injection in the volar wrist or posterior to the medial malleolus.

An immediate scan will be acquired using an ICG lymphography device. The scan will take approximately five minutes to complete. The data from this image will be considered baseline. This image is part of the patient's normal care at our institution and would be done even if the subject was not in this study.

The participant will then use the Nu-Step exercise machine for five minutes at a rate of perceived exertion (RPE) of 12-13. Heart rate will be monitored during the exercise with a pulse oximeter. After five minutes, a delayed scan will be performed with the NOVADAQ SPY Elite System and data will be recorded. The participant will continue to exercise for five minutes at an RPE of 12-13 and be scanned after every five minutes until the scans show no change in lymph pattern after two consecutive scans. The patient will be undergoing scanning and be exercising for a maximum of one hour.

Limb circumference measurements and bioimpedance scans will be repeated after exercise has been completed. The scan will be repeated every 1 hour until the normal 6-hour scan to monitor for further changes in the lymphatic pattern.

A post-intervention questionnaire will then be provided to the participant to complete discussing their exercise experience that day during the study, their previous ICG experiences, and their preference between this protocol and the current scanning process.

During the study, the subject will be told when he/she is being photographed/recorded. The injections and scans are clinically-indicated and would occur whether the individual was in the study or not. The initial and last scans are clinically indicated to determine disease status. 3) clarify how the follow-up survey is completed via email

Arms: arm 1: The subjects with lymphedema will be exercising on a Nu-Step exercise machine that will exercise their arms and legs simultaneously for five-minute intervals. Every five minutes their limbs will be imaged with Indocyanine Green Lymphography.
Interventions: intervention 1: Indocyanine Green
Intervention descriptions: intervention 1: The subjects will be exercising on a Nu-Step exercise machine that will exercise their arms and legs simultaneously for five-minute intervals. Every five minutes their limbs will be imaged with an ICG lymphography device to determine the plateau rate of indocyanine green dye after exercise.

Protocol documents:
Prot_SAP_002.pdf: 
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.