Lymphedema of LegNCT05242900
Imaging Sodium and Lymphatics in Lymphedema
An observational study of Lymphedema of Leg and Lymphedema, Secondary, run by University of Virginia at 1 site in United States.
Trial summary
Recent evidence supports lymphatic regulation of tissue sodium handling, however fundamental gaps persist in knowledge regarding the role of lymphatics in human diseases of sodium dysregulation. Read more about this study
- Who is it for?
- Ages 18 to 80 years, women only
- Conditions the study is for
- Lymphedema of Leg, Lymphedema, Secondary, Lymphedema Related Fibrosis
- What is being tested?
- Complete decongestive therapy and Standard imaging protocol
- Type of treatment
- Surgery or procedure
- How many people
- 75 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Oct 2021to Dec 2025
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 18 to 80 years
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: The investigators will recruit adults who are at-risk for lower-extremity lymphedema (n=30) or who have lower-extremity secondary lymphedema (n=45).
Who may be able to join
- Biologically Female
- Age range = 18-80 years
- BMI range = 18 to 40 kg/m2
Who cannot join
- Primary lymphedema
- Contraindication to 3T MRI
- Pregnant
- Severe claustrophobia
- Inability to provide written, informed consent
- Active infection anywhere in the body, or open wound on the lower-extremities or at locations for measurement
- Subjects who cannot adhere to the experimental protocols for any reason
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Virginia
Charlottesville, Virginia, 22903
About this study
Recent evidence supports lymphatic regulation of tissue sodium handling, however fundamental gaps persist in knowledge regarding the role of lymphatics in human diseases of sodium dysregulation. The goal of this work is to apply novel, noninvasive imaging tools to measure relationships between lymphatic function and tissue sodium in patients with well-characterized lymphedema. Findings are intended to inform mechanisms of lymphatic clearance of tissue sodium, and provide novel imaging biomarkers of lymphedema progression and treatment response.
Read the detailed description
The overall goal of this work is to apply and evaluate novel, noninvasive MRI technologies sensitive to sodium and lymphatic circulation in patients with well-characterized lymphatic disease. The results will clarify mechanisms of lymphatic clearance of tissue sodium, and evaluate novel biomarkers of lymphedema risk, progression, and treatment response. Recent evidence supports that lymphatics regulate interstitial sodium levels. When lymphatic clearance is impaired, hypertonic interstitial sodium results in tissue swelling, skin sodium storage, and poor blood pressure control. When lymphatic clearance is impaired in rodent models of lymphedema, lymph stasis and inflammation ensue, leading to tissue remodeling and fibrosis. These data suggest, but do not confirm, that impaired lymphatic clearance contributes to tissue sodium storage and fibrosis. However, this possibility has not been investigated rigorously owing to a lack of clinically-feasible measurement tools sensitive to sodium and lymphatics in humans. To address these gaps in knowledge, the investigators have developed a noninvasive MR lymphangiography (MRL) approach to quantify lymphatic vasculature in patients with unilateral lymphedema of the upper-extremities. They confirmed lateralized lymph stasis and enlarged lymphatic collector cross-sectional area that reduced following manual lymphatic drainage therapy. In parallel to these studies, the investigators optimized noninvasive sodium 23Na MRI for measurement of tissue sodium content (TSC) in the legs of patients with lymphatic insufficiency due to lipedema. In preliminary data, they demonstrate these methods together for the first time in patients with cancer-related lower-extremity lymphedema (LEL) who display significantly elevated skin TSC compared to controls (24.2±6.8 vs. 14.2±1.8 mmol/L, p<0.001, effect size Cohen's d=1.2). Evidence of lymphatic impairment on MRL and tissue sodium deposition are differential in patients with increasing disease severity, and modified by lymphatic complete decongestive therapy (CDT), motivating the following hypotheses:
Hypothesis (1): Skin TSC inversely correlates with lymphatic flow velocity; lymphatic flow velocity reduces and TSC increases following LN removal in patients at risk for lymphedema. Hypothesis (2): Skin TSC positively correlates with lymphedema stage; subcutaneous sodium co-localizes with fibrotic tissue in patients with lymphedema and fibrosis. Hypothesis (3): Skin TSC decreases and lymphatic flow velocity increases after CDT in affected limbs with LEL; imaging metrics are reproducible in healthy volunteers. Impact: Results will demonstrate relationships between tissue sodium and lymphatic dysfunction in human disease using noninvasive MRI technologies. This will outline clinically-feasible biomarkers of lymphedema risk, progression, and treatment response which could have significance for future clinical trials that seek to evaluate the impact of emerging lymphatic therapies on tissue sodium storage.
- Being tested
- Complete decongestive therapy, Standard imaging protocol
- Keywords
- MRI, sodium, lymphedema, adipose tissue, fibrosis
- Medical subject headings
- Lymphedema, Neoplasm Metastasis, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Complete decongestive therapyProcedure or surgery
Also called manual lymphatic drainage, compression, exercise
The investigators will identify participants undergoing clinically-indicated interventions that they are already receiving for their routine clinical management (complete decongestive physical therapy). They will make no evaluation of the efficacy of these procedures, but rather will test fundamental hypotheses regarding lymphatic clearance of tissue sodium.
Standard imaging protocolOther
The standard imaging protocol entails noninvasive magnetic resonance imaging techniques including sodium and lymphatic angiography.
| Study group | Role | What they receive |
|---|---|---|
| At-risk for lymphedema | Participants at-risk for leg lymphedema Receives: Other: Standard imaging protocol | |
| With lymphedema | Participants with leg lymphedema Receives: Other: Standard imaging protocol | |
| With lymphedema undergoing complete decongestive therapy (CDT) | Participants with leg lymphedema undergoing routine complete decongestive therapy (CDT) Receives: Procedure: Complete decongestive therapy; Other: Standard imaging protocol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Concentration of tissue sodium content
Research participants will undergo periodic noninvasive sodium MRI after clinically-indicated complete decongestive therapy. The study team will measure change in tissue sodium content (mmol/L) in the treated extremities to study effects of lymphatic stimulation on sodium clearance.
Measured: Baseline to completion of routine course of physical therapy (approximately 6 weeks)
Number of participants that changed lymphedema severity
Research participants will undergo periodic noninvasive magnetic resonance lymphangiography after clinically-indicated complete decongestive therapy. The study team will measure change in quantified lymphatic stasis in the treated extremities to study effects of lymphatic stimulation on lymphedema severity.
Measured: Baseline to completion of routine course of physical therapy (approximately 6 weeks)
Concentration of tissue sodium content baseline
For participants at-risk or with lymphedema, noninvasive sodium MRI will measure tissue sodium content (mmol/L) in the extremities to study sodium in lymphedema.
Measured: Baseline
Quantification of lymphatic states in extremities at baseline
For participants at-risk or with lymphedema, noninvasive MR lymphangiography will measure quantified lymphatic stasis in the extremities to study lymphatic physiology in lymphedema.
Measured: Baseline
Secondary outcomes (6)
Concentration in limb extracellular water
Research participants will undergo periodic assessment by bioimpedance spectroscopy to estimate limb extracellular water (whole-limb resistance, Ohms) after clinically-indicated complete decongestive therapy. The study team will measure change in limb extracellular water (whole-limb resistance, Ohms) in the treated extremities to study effects of lymphatic stimulation on tissue composition.
Measured: Baseline and after a routine course of physical therapy (approximately 6 weeks)
Concentration in skin water
Research participants will undergo periodic assessment by tissue dielectric probe to estimate skin water (% water) after clinically-indicated complete decongestive therapy. The study team will measure change in skin water (% water) in the treated extremities to study effects of lymphatic stimulation on tissue composition.
Measured: Baseline and after a routine course of physical therapy (approximately 6 weeks)
Change in skin elasticity
Research participants will undergo periodic assessment by fibrometer probe to estimate skin elasticity (Newtons of induration) after clinically-indicated complete decongestive therapy. The study team will measure change in skin elasticity (Newtons of induration) in the treated extremities to study effects of lymphatic stimulation on tissue composition.
Measured: Baseline and after a routine course of physical therapy (approximately 6 weeks)
Concentration of limb extracellular water at baseline
For participants at-risk or with lymphedema, baseline limb extracellular water (whole-limb resistance, Ohms) will be estimated in the extremities to study tissue composition in lymphedema.
Measured: Baseline
Baseline skin water
For participants at-risk or with lymphedema, baseline skin water (% water) will be estimated in the extremities to study tissue composition in lymphedema.
Measured: Baseline
Baseline skin elasticity
For participants at-risk or with lymphedema, baseline skin elasticity (Newtons of induration) will be estimated in the extremities to study tissue composition in lymphedema.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2022
- Study start10 Oct 2021
- Primary completionDec 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lymphedema of LegStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 75 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Vanderbilt University Medical Center
- Responsible party
- Principal investigator, Rachelle Crescenzi, University of Virginia
- Investigators
- Rachelle Crescenzi, PhD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05242900
- Sponsor's protocol ID
- 302403
- Other IDs
- 1R01HL155523-01, 202424
- Status last verified
- Apr 2025
- First submitted
- 7 Dec 2021
- Last updated
- 27 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Imaging Sodium and Lymphatics in Lymphedema
- ClinicalTrials.gov ID
- NCT05242900
- Acronym / sponsor ID
- 302403
- Keywords
- MRI, sodium, lymphedema, adipose tissue, fibrosis
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Vanderbilt University Medical Center
- Study start
- 10 Oct 2021 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 16 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Recent evidence supports lymphatic regulation of tissue sodium handling, however fundamental gaps persist in knowledge regarding the role of lymphatics in human diseases of sodium dysregulation. The goal of this work is to apply novel, noninvasive imaging tools to measure relationships between lymphatic function and tissue sodium in patients with well-characterized lymphedema. Findings are intended to inform mechanisms of lymphatic clearance of tissue sodium, and provide novel imaging biomarkers of lymphedema progression and treatment response.
Detailed description
The overall goal of this work is to apply and evaluate novel, noninvasive MRI technologies sensitive to sodium and lymphatic circulation in patients with well-characterized lymphatic disease. The results will clarify mechanisms of lymphatic clearance of tissue sodium, and evaluate novel biomarkers of lymphedema risk, progression, and treatment response. Recent evidence supports that lymphatics regulate interstitial sodium levels. When lymphatic clearance is impaired, hypertonic interstitial sodium results in tissue swelling, skin sodium storage, and poor blood pressure control. When lymphatic clearance is impaired in rodent models of lymphedema, lymph stasis and inflammation ensue, leading to tissue remodeling and fibrosis. These data suggest, but do not confirm, that impaired lymphatic clearance contributes to tissue sodium storage and fibrosis. However, this possibility has not been investigated rigorously owing to a lack of clinically-feasible measurement tools sensitive to sodium and lymphatics in humans. To address these gaps in knowledge, the investigators have developed a noninvasive MR lymphangiography (MRL) approach to quantify lymphatic vasculature in patients with unilateral lymphedema of the upper-extremities. They confirmed lateralized lymph stasis and enlarged lymphatic collector cross-sectional area that reduced following manual lymphatic drainage therapy. In parallel to these studies, the investigators optimized noninvasive sodium 23Na MRI for measurement of tissue sodium content (TSC) in the legs of patients with lymphatic insufficiency due to lipedema. In preliminary data, they demonstrate these methods together for the first time in patients with cancer-related lower-extremity lymphedema (LEL) who display significantly elevated skin TSC compared to controls (24.2±6.8 vs. 14.2±1.8 mmol/L, p<0.001, effect size Cohen's d=1.2). Evidence of lymphatic impairment on MRL and tissue sodium deposition are differential in patients with increasing disease severity, and modified by lymphatic complete decongestive therapy (CDT), motivating the following hypotheses:
Hypothesis (1): Skin TSC inversely correlates with lymphatic flow velocity; lymphatic flow velocity reduces and TSC increases following LN removal in patients at risk for lymphedema. Hypothesis (2): Skin TSC positively correlates with lymphedema stage; subcutaneous sodium co-localizes with fibrotic tissue in patients with lymphedema and fibrosis. Hypothesis (3): Skin TSC decreases and lymphatic flow velocity increases after CDT in affected limbs with LEL; imaging metrics are reproducible in healthy volunteers. Impact: Results will demonstrate relationships between tissue sodium and lymphatic dysfunction in human disease using noninvasive MRI technologies. This will outline clinically-feasible biomarkers of lymphedema risk, progression, and treatment response which could have significance for future clinical trials that seek to evaluate the impact of emerging lymphatic therapies on tissue sodium storage.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| At-risk for lymphedema | – | Other: Standard imaging protocolParticipants at-risk for leg lymphedema |
| With lymphedema | – | Other: Standard imaging protocolParticipants with leg lymphedema |
| With lymphedema undergoing complete decongestive therapy (CDT) | – | Procedure: Complete decongestive therapy, Other: Standard imaging protocolParticipants with leg lymphedema undergoing routine complete decongestive therapy (CDT) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The investigators will recruit adults who are at-risk for lower-extremity lymphedema (n=30) or who have lower-extremity secondary lymphedema (n=45).
Key inclusion criteria (3 listed)
- Biologically Female
- Age range = 18-80 years
- BMI range = 18 to 40 kg/m2
Key exclusion criteria (7 listed)
- Primary lymphedema
- Contraindication to 3T MRI
- Pregnant
- Severe claustrophobia
- Inability to provide written, informed consent
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 |
|---|---|---|
| Complete decongestive therapyAlso: manual lymphatic drainage, compression, exerciseThe investigators will identify participants undergoing clinically-indicated interventions that they are already receiving for their routine clinical management (complete decongestive physical therapy). They will make no evaluation of the efficacy of these procedures, but rather will test fundamental hypotheses regarding lymphatic clearance of tissue sodium. | Procedure or surgery | With lymphedema undergoing complete decongestive therapy (CDT) |
| Standard imaging protocolThe standard imaging protocol entails noninvasive magnetic resonance imaging techniques including sodium and lymphatic angiography. | Other | At-risk for lymphedema, With lymphedema, With lymphedema undergoing complete decongestive therapy (CDT) |
Primary outcome
Concentration of tissue sodium content
Time frame: Baseline to completion of routine course of physical therapy (approximately 6 weeks)
Research participants will undergo periodic noninvasive sodium MRI after clinically-indicated complete decongestive therapy. The study team will measure change in tissue sodium content (mmol/L) in the treated extremities to study effects of lymphatic stimulation on sodium clearance.
Number of participants that changed lymphedema severity
Time frame: Baseline to completion of routine course of physical therapy (approximately 6 weeks)
Research participants will undergo periodic noninvasive magnetic resonance lymphangiography after clinically-indicated complete decongestive therapy. The study team will measure change in quantified lymphatic stasis in the treated extremities to study effects of lymphatic stimulation on lymphedema severity.
Concentration of tissue sodium content baseline
Time frame: Baseline
For participants at-risk or with lymphedema, noninvasive sodium MRI will measure tissue sodium content (mmol/L) in the extremities to study sodium in lymphedema.
Quantification of lymphatic states in extremities at baseline
Time frame: Baseline
For participants at-risk or with lymphedema, noninvasive MR lymphangiography will measure quantified lymphatic stasis in the extremities to study lymphatic physiology in lymphedema.
6 secondary outcomes
Concentration in limb extracellular water
Time frame: Baseline and after a routine course of physical therapy (approximately 6 weeks)
Concentration in skin water
Time frame: Baseline and after a routine course of physical therapy (approximately 6 weeks)
Change in skin elasticity
Time frame: Baseline and after a routine course of physical therapy (approximately 6 weeks)
Concentration of limb extracellular water at baseline
Time frame: Baseline
Baseline skin water
Time frame: Baseline
Baseline skin elasticity
Time frame: Baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2025.
- Individual participant dataSharing planned: Undecided
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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.
Rachelle Crescenzi, PhD principal investigator
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Lymphedema of Leg and Lymphedema, Secondary, run by University of Virginia 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 3 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: under way, not looking for participants, as of the sponsor's last update on 27 Apr 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?
This study is still under way. Results are not available in the source record yet.
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?
Concentration of tissue sodium content (time frame: Baseline to completion of routine course of physical therapy (approximately 6 weeks)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Apr 2025; AzTrials last refreshed its copy on 6 Nov 2026.