Imaging Biomarkers of Lymphatic Dysfunction

NCT ID: NCT03760744

Last Updated: 2025-10-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-23
• Study Completion Date: 2025-03-15

Brief Summary

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.

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.

Conditions

Secondary Lymphedema

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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)

Group Type: EXPERIMENTAL

CDT with Negative Pressure

Intervention Type: PROCEDURE

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

CDT alone

Intervention Type: PROCEDURE

Complete decongestive therapy (physical therapy conservative intervention of compression, manual lymphatic drainage, skin care and exercises) for lymphatic stimulation/ tissue clearance

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)

Group Type: ACTIVE_COMPARATOR

CDT with Negative Pressure

Intervention Type: PROCEDURE

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

CDT alone

Intervention Type: PROCEDURE

Complete decongestive therapy (physical therapy conservative intervention of compression, manual lymphatic drainage, skin care and exercises) for lymphatic stimulation/ tissue clearance

Interventions

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

Intervention Type: PROCEDURE

CDT alone

Complete decongestive therapy (physical therapy conservative intervention of compression, manual lymphatic drainage, skin care and exercises) for lymphatic stimulation/ tissue clearance

Intervention Type: PROCEDURE

Other Intervention Names

CDT with LymphaTouch; Complete decongestive therapy without negative pressure

Eligibility Criteria

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.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Institute of Nursing Research (NINR)

NIH

Sponsor Role: collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Manus Donahue

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Manus M Donahue, PhD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 28323572 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28245075 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1R01NR015079

Identifier Type: NIH

Identifier Source: secondary_id

View Link

3760744

Identifier Type: -

Identifier Source: org_study_id