Imaging Biomarkers of Lymphatic Dysfunction

Persons with secondary arm and/or upper quadrant lymphedema following cancer therapies commonly are prescribed complete decongestive therapy as a course of management of their lymphedema. The investigators will perform a repeated-measures cross-over trial to test the hypothesis that mobilization of protein enriched hardened tissue using graded negative pressure therapy in conjunction with complete decongestive therapy (CDT) is more effective to standard CDT alone for secondary lymphedema management.

Study Overview

• Status: Completed
• Conditions: Secondary Lymphedema
• Intervention / Treatment: Procedure: CDT with Negative Pressure; Procedure: CDT alone

Detailed Description

The goal of this work is to apply novel, noninvasive magnetic resonance imaging (MRI) methods for visualizing lymphatic circulation dysfunction to test a fundamental hypothesis about secondary lymphedema conservative decongestive therapy. Breast cancer treatment-related lymphedema (BCRL) arises secondary to surgical axillary lymph node (LN) dissection and irritation, and is a chronic and lifelong condition affecting a high 21.4% of patients receiving common breast cancer therapies. Persons with secondary lymphedema following axillary lymph node removal also include undergoing treatment for other cancers, such as melanoma involving the upper body, necessitating the need for axially lymph node removal.

Improving lymphedema management represents a major clinical need, and emerging efforts focus on improving quality of life through optimizing post-surgical complex decongestive therapy (CDT), and exploring novel pharmacological and surgical procedures. Here, the investigators will perform a repeated-measures cross-over trial to test the hypothesis that mobilization of protein enriched hardened tissue using graded negative pressure therapy in conjunction with complete decongestive therapy (CDT) is more effective to standard CDT alone for secondary lymphedema management. Both of these conservative physical therapy treatments are commonly employed for treatment of secondary lymphedema.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Females with a diagnosis of secondary arm and/or upper quadrant lymphedema following cancer treatments

Exclusion Criteria:

• Subjects who have any type of non-MRI compatible bioimplant activated by mechanical, electronic, or magnetic means (e.g., cochlear implants, pacemakers, neurostimulators, biostimulators, electronic infusion pumps, etc.) or are not able to comfortably be able to tolerate the limited fit of the MRI
• Subjects who have any type of ferromagnetic bioimplant that could potentially be displaced.
• Subjects who may have shrapnel embedded in their bodies (such as from war wounds), metal workers and machinists (potential for metallic fragments in or near the eyes).
• Pregnant women will be excluded from the MRI portion of the study only
• Subjects who have open wounds on either ankle or top of foot because of contraindications with placement of electrodes to obtain the L-DEX U400 readings.
• Persons with heart pacemakers.
• Persons with bilateral arm lymphedema (or bilateral risk) or pre-existing lymphedema/edema in the upper body prior to cancer treatments.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CDT Alone first, then CDT With Negative Pressure; Participants randomized into a CDT alone without LymphaTouch for 6 weeks, total of 9 therapy visits (75minutes duration). This is followed by a 6 month washout period, then a second intervention consisting of CDT with LymphaTouch for 6 weeks, total of 9 therapy visits (75minutes duration)	Procedure: CDT with Negative Pressure; Complete decongestive therapy (physical therapy conservative intervention of compression, manual lymphatic drainage, skin care and exercises) in conjunction with manual intervention of graded negative pressure application for lymphatic stimulation/ tissue clearance; Other Names: CDT with LymphaTouch; Procedure: CDT alone; Complete decongestive therapy (physical therapy conservative intervention of compression, manual lymphatic drainage, skin care and exercises) for lymphatic stimulation/ tissue clearance; Other Names: Complete decongestive therapy without negative pressure
Active Comparator: CDT With Negative Pressure first, then CDT Alone; Participants randomized into a CDT with LymphaTouch Negative Pressure for 6 weeks, total of 9 therapy visits (75minutes duration). This is followed by a 6 month washout period, then a second intervention consisting of CDT alone without Negative Pressure for 6 weeks, total of 9 therapy visits (75minutes duration)	Procedure: CDT with Negative Pressure; Complete decongestive therapy (physical therapy conservative intervention of compression, manual lymphatic drainage, skin care and exercises) in conjunction with manual intervention of graded negative pressure application for lymphatic stimulation/ tissue clearance; Other Names: CDT with LymphaTouch; Procedure: CDT alone; Complete decongestive therapy (physical therapy conservative intervention of compression, manual lymphatic drainage, skin care and exercises) for lymphatic stimulation/ tissue clearance; Other Names: Complete decongestive therapy without negative pressure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessing a Change in Bioimpedance Spectroscopy (BIS)	BIS is a noninvasive technology measuring the resistance and reactance of tissue across multiple electrical frequencies using the Impedimed U400 device. By distinguishing ICF from ECF, BIS allows sensitive detection of ECF accumulation, a hallmark of lymphedema. Impedimed's proprietary calculations convert impedance ratios of limbs (involved vs unaffected) into a single output known as LDEX (lymphedema index) with an output normal range of -10 to +10. In situations of overt signs of lymphedema, the LDEX value could be up to 120. This single output value (LDEX) is used in lymphedema research and clinical care to monitor lymphedema progress and response to lymphedema therapy. The LDEX outcome in this study represents the change in LDEX value of the arms from study baseline and at 6-8 weeks following the completion of therapy where a negative value shows a positive response from the therapy intervention by indicating a reduction in the LDEX value.	At baseline and at 6-8 weeks following the completion of therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessing a Change in Quality of Life Via Patient Specific Functional Scale (PSFS)	The Patient Specific Functional Scale (PSFS) was developed as a self-report outcome measure of function that could be used in participants with varying levels of independence. Each participant chose a set of three daily activities and rated the level of ease and comfort with which they could complete them pre and post each intervention. Rating scale starts at 0 (unable to perform activity) and goes to goes up to 10 (able to perform activity at the same level as before injury or problem). The closer to 10, the more favorable the number is.	At baseline (pre-intervention) and at 6-8 weeks following the completion of each therapy (post-intervention)
Tissue Dielectric Constant (TDC) Measurement Difference Above the Elbow	TDC measures the skin-to-fat water content in tissues. The location was chosen given the propensity of swelling and discomfort in the area for participant population. This measurement compares the TDC value in the affected limb versus the unaffected limb, therefore the closer the TDC measurement difference is to zero, the more favorable the value is.	At baseline (pre-intervention) and at 6-8 weeks following the completion of each therapy ([post intervention )

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: National Institute of Nursing Research (NINR); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Manus M Donahue, PhD, Vanderbilt University Medical Center

Publications and helpful links

General Publications

• Donahue PM, Crescenzi R, Scott AO, Braxton V, Desai A, Smith SA, Jordi J, Meszoely IM, Grau AM, Kauffmann RM, Sweeting RS, Spotanski K, Ridner SH, Donahue MJ. Bilateral Changes in Deep Tissue Environment After Manual Lymphatic Drainage in Patients with Breast Cancer Treatment-Related Lymphedema. Lymphat Res Biol. 2017 Mar;15(1):45-56. doi: 10.1089/lrb.2016.0020.
• Crescenzi R, Donahue PMC, Hartley KG, Desai AA, Scott AO, Braxton V, Mahany H, Lants SK, Donahue MJ. Lymphedema evaluation using noninvasive 3T MR lymphangiography. J Magn Reson Imaging. 2017 Nov;46(5):1349-1360. doi: 10.1002/jmri.25670. Epub 2017 Feb 28.

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2019
• Primary Completion (Actual): March 15, 2025
• Study Completion (Actual): March 15, 2025

Study Registration Dates

• First Submitted: November 28, 2018
• First Submitted That Met QC Criteria: November 28, 2018
• First Posted (Actual): November 30, 2018

Study Record Updates

• Last Update Posted (Estimated): October 16, 2025
• Last Update Submitted That Met QC Criteria: September 26, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: lymphedema; therapy; swelling; complete decongestive therapy; graded negative pressure
• Additional Relevant MeSH Terms: Lymphatic Diseases; Hemic and Lymphatic Diseases; Lymphedema; carbohydrate-deficient transferrin
• Other Study ID Numbers: 3760744; 1R01NR015079 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No