Secondary LymphedemaNCT03760744

Imaging Biomarkers of Lymphatic Dysfunction

A study testing CDT with Negative Pressure and CDT alone in people with Secondary Lymphedema, run by Vanderbilt University Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 30 to 90 years, women only
Conditions the study is for: Secondary Lymphedema
What is being tested?: CDT with Negative Pressure and CDT alone
Type of treatment: Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 18 participants
Where: 1 siteUnited States
Study dates: 23 Jan 2019to 15 Mar 2025
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 30 to 90 years
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Vanderbilt University Medical Center
Nashville, Tennessee, 37212

Other trials in United States

About this study

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.

Read the 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
Being tested: CDT with Negative Pressure, CDT alone
Keywords: lymphedema, therapy, swelling, graded negative pressure, complete decongestive therapy
Medical subject headings: Lymphedema

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CDT with Negative PressureProcedure or surgery
Also called CDT with LymphaTouch
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 aloneProcedure or surgery
Also called Complete decongestive therapy without negative pressure
Complete decongestive therapy (physical therapy conservative intervention of compression, manual lymphatic drainage, skin care and exercises) for lymphatic stimulation/ tissue clearance

Study groups in NCT03760744
Study group	Role	What they receive
CDT Alone first, then CDT With Negative Pressure	Experimental	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) Receives: Procedure: CDT with Negative Pressure; Procedure: CDT alone
CDT With Negative Pressure first, then CDT Alone	Active comparator	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) Receives: Procedure: CDT with Negative Pressure; Procedure: CDT alone

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: At baseline and at 6-8 weeks following the completion of therapy

Secondary outcomes (2)

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.
Measured: 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.
Measured: At baseline (pre-intervention) and at 6-8 weeks following the completion of each therapy ([post intervention )

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Jan 201915 Mar 2025

First posted30 Nov 2018
Study start23 Jan 2019
Primary completion15 Mar 2025
Study completion15 Mar 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Secondary LymphedemaStudies of the same condition, open and under way.
More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Investigator, Outcomes assessor
Enrolment: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03760744
Sponsor's protocol ID: 3760744
Other IDs: 1R01NR015079
Status last verified: Sep 2025
First submitted: 28 Nov 2018
Last updated: 16 Oct 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

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.
PubMed 28323572
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.
PubMed 28245075
Donahue MJ, Donahue PMC, Jones RS, Garza M, Lee C, Patel NJ, Cooper A, De Vis JB, Meszoely I, Crescenzi R. In vivo lymph node CEST-Dixon MRI in breast cancer patients with metastatic lymph node involvement. Magn Reson Med. 2024 Feb;91(2):670-680. doi: 10.1002/mrm.29858. Epub 2023 Sep 8.
PubMed 37684712

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
Lymphovenous Bypass Procedure for Secondary Prevention of Lymphedema in Breast Cancer
Lymphedema Arm
RecruitingObservational study
Use of Reconstructive Microsurgery for the Treatment of Lymphedema
Lymphedema
Not yet recruitingPhase 1/2
mRNA Therapy to Restore Lymphatic Flow in Secondary Lymphedema
Secondary Lymphedema
Not yet recruitingObservational study
Biological Profile of Primary and Secondary Lymphedema: Inflammatory, Endothelial, Metabolic, Lymphatic, and Fibrotic Markers
Primary Lymphedema, Secondary Lymphedema
RecruitingPhase 2
IIT2023-09-Chung-UpfrontTAD: Upfront TAD/SNB in Patients With Breast Cancer With Nodal Metastases
Breast Cancer, Axillary Nodal Disease

All Secondary Lymphedema trials

Study at a glance

From the registry record, last updated by the sponsor on 16 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Imaging Biomarkers of Lymphatic Dysfunction
ClinicalTrials.gov ID: NCT03760744
Acronym / sponsor ID: 3760744
Conditions: Secondary Lymphedema
Keywords: lymphedema, therapy, swelling, graded negative pressure, complete decongestive therapy
Study type: Interventional
Recruitment status: Completed
Enrolment: 18 participants (actual)
Lead sponsor: Vanderbilt University Medical CenterUniversity, hospital or other
Collaborators: National Institutes of Health (NIH), National Institute of Nursing Research (NINR)
Study start: 23 Jan 2019 (actual)
Primary completion: 15 Mar 2025 (actual)
Study completion: 15 Mar 2025 (actual)
First posted: 30 Nov 2018 (actual)
Results: Posted 16 Oct 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
CDT Alone first, then CDT With Negative Pressure	Experimental	Procedure: CDT with Negative Pressure, Procedure: CDT aloneParticipants 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)
CDT With Negative Pressure first, then CDT Alone	Active comparator	Procedure: CDT with Negative Pressure, Procedure: CDT aloneParticipants 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)

Who may qualify

Ages: 30 to 90 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (1 listed)

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

Key exclusion criteria (7 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CDT with Negative PressureAlso: CDT with LymphaTouchComplete 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	Procedure or surgery	CDT Alone first, then CDT With Negative Pressure, CDT With Negative Pressure first, then CDT Alone
CDT aloneAlso: Complete decongestive therapy without negative pressureComplete decongestive therapy (physical therapy conservative intervention of compression, manual lymphatic drainage, skin care and exercises) for lymphatic stimulation/ tissue clearance	Procedure or surgery	CDT Alone first, then CDT With Negative Pressure, CDT With Negative Pressure first, then CDT Alone

Primary outcome

Assessing a Change in Bioimpedance Spectroscopy (BIS)
Time frame: At baseline and at 6-8 weeks following the completion of therapy
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.

2 secondary outcomes

Assessing a Change in Quality of Life Via Patient Specific Functional Scale (PSFS)
Time frame: 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
Time frame: At baseline (pre-intervention) and at 6-8 weeks following the completion of each therapy ([post intervention )

Results and safety

Results posted to the registry on 16 Oct 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
CDT Alone First, Then CDT With Negative Pressure	9	6
CDT With Negative Pressure First, Then CDT Alone	9	9

Primary outcome: Assessing a Change in Bioimpedance Spectroscopy (BIS)

Time frame: At baseline and at 6-8 weeks following the completion of therapy. Mean (Standard Deviation). Unit: Change of score on a scale

Measure	CDT Alone n = 15	CDT With Negative Pressure n = 15
Value	1.3 (8)	1.8 (5.1)

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 2 years, 4 months.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
CDT Alone	0 of 15 (0%)	0 of 15 (0%)	0 of 15
CDT With Negative Pressure	0 of 15 (0%)	0 of 15 (0%)	0 of 15

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 28323572Donahue 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.
Background: PubMed 28245075Crescenzi 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.
Derived from this study: PubMed 37684712Donahue MJ, Donahue PMC, Jones RS, Garza M, Lee C, Patel NJ, Cooper A, De Vis JB, Meszoely I, Crescenzi R. In vivo lymph node CEST-Dixon MRI in breast cancer patients with metastatic lymph node involvement. Magn Reson Med. 2024 Feb;91(2):670-680. doi: 10.1002/mrm.29858. Epub 2023 Sep 8.
Individual participant dataSharing planned: No

Related trials for Secondary Lymphedema

Recruiting
Lymphovenous Bypass Procedure for Secondary Prevention of Lymphedema in Breast Cancer
Lymphedema Arm
RecruitingObservational study
Use of Reconstructive Microsurgery for the Treatment of Lymphedema
Lymphedema
Not yet recruitingPhase 1/2
mRNA Therapy to Restore Lymphatic Flow in Secondary Lymphedema
Secondary Lymphedema
Not yet recruitingObservational study
Biological Profile of Primary and Secondary Lymphedema: Inflammatory, Endothelial, Metabolic, Lymphatic, and Fibrotic Markers
Primary Lymphedema, Secondary Lymphedema
RecruitingPhase 2
IIT2023-09-Chung-UpfrontTAD: Upfront TAD/SNB in Patients With Breast Cancer With Nodal Metastases
Breast Cancer, Axillary Nodal Disease

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Manus M Donahue, PhD principal investigator

Vanderbilt University Medical Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing CDT with Negative Pressure and CDT alone in people with Secondary Lymphedema, run by Vanderbilt University Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Assessing a Change in Bioimpedance Spectroscopy (BIS) (time frame: At baseline and at 6-8 weeks following the completion of therapy). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03760744, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2025.