Study of Lymphatic Dysfunction in Primary and Secondary Lymphedema (LYMPHODYS)

Lymphedema is a disorder of the lymphatic vascular system characterized by impaired lymphatic return and swelling of the extremities and accumulation of undrained interstitial fluid/lymph that results in fibrosis and adipose tissue deposition in the affected area. It can be an inherited condition (primary lymphedema) or occurs after cancer surgery and lymph node removal (secondary lymphedema). It causes a significant morbidity and is a common disabling disease affecting more than 200 million people worldwide, however there is no curative treatment for primary or secondary lymphedema.

Study Overview

• Status: Recruiting
• Conditions: Lymphedema
• Intervention / Treatment: Procedure: Micro-biopsies

Detailed Description

Primary lymphedema is an inherited condition whereas secondary lymphedema develops after cancer treatments. Despite common phenotype, a molecular and histological comparison of these two pathologies has never been performed. Primary lymphedema is associated with heterozygous inactivating mutations of the gene encoding vascular endothelial growth factor C and D receptor (VEGFR-3). Primary lymphedema is rare, affecting 1 in 100,000 individuals. Secondary lymphedema is the most common cause of the disease and affects more than 200 million people worldwide.

Secondary lymphedema occurs months, sometimes years after cancer surgery suggesting that lymphedema is not only a side effect of the surgery, but involves modifications of the lymphatic architecture as well as its microenvironment, in particular adipose tissue that accumulates in the limb.

There is no cure for lymphedema because of the lack of identified therapeutic strategies able to restore collecting lymphatic draining function in the arm or in the leg. The goal will be to establish if these pathologies which possess a common denomination exhibit a similar gene expression.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Julie MALLOIZEL-DELAUNAY, MD; Phone Number: +33 (0)5 61 32 30 33; Email: malloizel-delaunay.j@chu-toulouse.fr
• Study Contact Backup: Name: Charline DAGUZAN; Phone Number: +33 (0)5 61 77 84 99; Email: daguzan.c@chu-toulouse.fr

Study Locations

• France
  • Toulouse, France
    • Recruiting
    • Toulouse Hospital
    • Contact: Julie MALLOIZEL-DELAUNAY, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients in who developed primary lymphedema or secondary lymphedema after breast cancer treatment.
2. Male and female over the age of 18 and under 75.
3. Patient affiliated to a social security scheme in France.
4. Patient having signed informed consent prior to inclusion in the study and prior to any specific procedure for the study.
5. Patients with no recidive > 3 years after cancer surgery.
6. Patients with Body Mass Index <35.
7. Patient enrolled in a care pathway for the management of their lymphedema (medical and educational care).
8. Patients wearing a compression orthosis on the limb with lymphedema.

Exclusion Criteria:

1. Patients with strong suspicion or with active bacterial or fungal infection.
2. Patient with venous insufficiency associated with lymphedema.
3. Patient with a history of deep venous thrombosis on the limb with lymphedema.
4. History of chronic inflammatory disease.
5. Active neoplasia during parallel management.
6. Patient already included in another therapeutic trial.
7. Pregnant or breastfeeding woman.
8. Metastatic cancer.
9. Bilateral breast cancer.
10. Obliterative arterial disease.
11. Multiple erysipelas.
12. Active smoking (delayed healing).
13. Medicines that may promote delayed healing (Corticosteroid therapy, immunosuppressants).
14. Medication that thins the blood (aspirin and antiplatelet agent, anti-coagulant).
15. Betadine allergy.
16. Patient under guardianship or trusteeship, persons placed under the protection of justice

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: primary lymphoedema; patients with primary lymphoedema	Procedure: Micro-biopsies; Two micro-biopsies of limb tissue will be carried out, one on the lymphedema and one in the upper limb not affected.
Experimental: secondary lymphoedema; patients with secondary lymphoedema	Procedure: Micro-biopsies; Two micro-biopsies of limb tissue will be carried out, one on the lymphedema and one in the upper limb not affected.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of RNA transcripts between lymphoedema limb and healthy limb	The gene expression profile of primary and secondary lymphedema will be determined by high-throughput RNA sequencing (RNAseq) or next-generation sequencing (NGS). It is a molecular methodology that allows the rapid sequencing of thousands to millions of RNA molecules simultaneously, determining the unique and specific order of nucleic acid bases. It is a random sequencing of the whole transcriptome which is used to identify and quantify the RNA resulting from the transcription of the genome at a given time.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LYVE-1 expression in primary and secondary lymphedema by immuno-histology	LYVE-1 (lymphatic vessel endothelial hyaluronan receptor-1) will be determined from immunodetection and staining performed on paraffin sections of lymphedema tissue in comparison with healthy tissue	Day 1
Podoplanin expression in primary and secondary lymphedema by immuno-histology	Podoplanin expression will be determined from immunodetection and staining performed on paraffin sections of lymphedema tissue in comparison with healthy tissue	Day 1
Chromatography analysis of Lipids in adipose tissues from primary and secondary lymphoedema	To describe lipid profile in adipose tissues from primary and secondary lymphoedema, in comparison to the healthy limb by chromatography analysis expressed in pg lipid/mg protein.	Day 1

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Julie MALLOIZEL-DELAUNAY, MD, University Hospital, Toulouse

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2024
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: October 3, 2022
• First Submitted That Met QC Criteria: November 16, 2022
• First Posted (Actual): November 29, 2022

Study Record Updates

• Last Update Posted (Actual): December 31, 2025
• Last Update Submitted That Met QC Criteria: December 23, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Lymphatic Diseases; Hemic and Lymphatic Diseases; Lymphedema
• Other Study ID Numbers: RC31/22/0128

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