Development of a Clinical Screening, Diagnostic and Evaluation Tool for Patients With Lower Limb Lymphedema: Aim 3 (EvaLymph-Leg3)

Development of a Clinical Screening, Diagnostic and Evaluation Tool for Patients With Lower Limb Lymphedema: Development of a Diagnostic Set for Patients With LLL

The current best practice is a three-stage classification consensus guideline as published by the International Society of Lymphology (ISL). Severity of lymphedema is however not only determined by presence of pitting (which is the phenomenon when the swollen area has a dimple (or pit) after you press it for 5 to 10 seconds) and presence of adipose tissue or not, but is also determined by the volume of the edema, a quantification of the condition of the skin and the location/expansion of the edema over the body. Currently a severity score considering these different aspects does not exist. Although there is consensus that the ISL staging systems is a necessary part of the diagnosis of lymphedema, it gives not enough information about the severity of the lymphedema. A more detailed and comprehensive classification system applicable for primary and secondary lymphedema and considering multiple edema characteristics, remains to be formulated.

The researchers objective in this study is to develop a diagnostic set, including a 'severity score', for patients with LLL.

Study Overview

• Status: Recruiting
• Conditions: Lower Limb Lymphedema
• Intervention / Treatment: Diagnostic test: Lower Limb Lymhedema assessment

• Study Type: Observational
• Enrollment (Estimated): 140

Contacts and Locations

• Study Contact: Name: Nele Devoogdt, Prof. Dr.; Phone Number: 003216342514; Email: nele.devoogdt@kuleuven.be
• Study Contact Backup: Name: Tessa De Vrieze, Dr.; Phone Number: 003216345006; Email: tessa.devrieze@kuleuven.be

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • University Hospitals of Leuven
    • Contact: Tessa De Vrieze, Dr.; Phone Number: 003216345006; Email: tessa.devrieze@kuleuven.be
• Netherlands
  • Drachten, Netherlands, 9202
    • Not yet recruiting
    • Nij Smellinghe hospital
    • Contact: Ad Hendrickx, PhD; Email: a.hendrickx@nijsmellinghe.nl
    • Contact: Robert Damstra, PhD; Email: r.damstra@nijsmellinghe.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Patients with LLL will be recruited in the center for lymphedema in UH Leuven in Belgium and in the center for lymphedema in Nij Smellinghe Hospital in Drachten in the Netherlands.

Healthy volunteers, both in Belgium as well as in the Netherlands.

Description

Inclusion Criteria:

Patient group

• Unilateral or bilateral, primary or secondary LLL
• Objective diagnosis of lymphedema: ≥ 5% volume difference between both legs OR ≥ 2 minor/ 1 major criteria on lymphoscintigraphy OR presence of ICG dermal backflow
• Age ≥ 18 years
• Able to read, understand and speak Dutch

Healthy controls

- Age, gender & BMI-matched healthy controls

Exclusion Criteria:

• Pregnant participants
• Presence of chronic venous insufficiency C4, C5, C6; deep venous thrombosis; post-thrombotic syndrome
• Presence of skin infections of wounds at the level of the lower limbs at the moment of inclusion

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
healthy controls	Diagnostic test: Lower Limb Lymhedema assessment; assessessment with the selected measurement methods showing sufficient reliability and feasibility in the patient group with LLL from aim 1:NCT05269264. Measurement will occur at the genital/midline region, and on both legs/ feet.
patients with unilateral or bilateral, primary or secundary LLL	Diagnostic test: Lower Limb Lymhedema assessment; assessessment with the selected measurement methods showing sufficient reliability and feasibility in the patient group with LLL from aim 1:NCT05269264. Measurement will occur at the genital/midline region, and on both legs/ feet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of measurement methods (resulted from aim 1:NCT05269264) in diagnosing unilateral and bilateral LLL	all patients with LLL and all healthy controls will be assessed with the selected measurement methods showing sufficient reliability and feasibility in the patient group with LLL from aim 1. Measurement will occur at the genital/midline region, and on both legs/ feet.	During the recruitment period (up to 1 year), patients are scheduled for only 1 visit with duration of +/- 1 hour (cross-sectional design)
Specificity of measurement methods (resulted from aim 1:NCT05269264) in diagnosing unilateral and bilateral LLL	all patients with LLL and all healthy controls will be assessed with the selected measurement methods showing sufficient reliability and feasibility in the patient group with LLL from aim 1. Measurement will occur at the genital/midline region, and on both legs/ feet.	During the recruitment period (up to 1 year), patients are scheduled for only 1 visit with duration of +/- 1 hour (cross-sectional design)
Diagnostic accuracy of measurement methods (resulted from aim 1:NCT05269264) in diagnosing unilateral and bilateral LLL	all patients with LLL and all healthy controls will be assessed with the selected measurement: methods showing sufficient reliability and feasibility in the patient group with LLL from aim 1. Measurement will occur at the genital/midline region, and on both legs/ feet. To determine diagnostic accuracy of the diagnostic methods, in a first phase, data will be analysed using Receiver Operating Characteristic (ROC) curves and by calculation the area under the curve (AUC) for each individual evaluation method resulting from aim 1. Sensitivity and specificity values will be compared, and for each measurement method, the AUC (or C-statistic) will be considered. Also prognostic values and likelihood ratios will be calculated of the individual measurement methods. Lastly, to investigate discriminant validity, measurement outcomes of the patients with LLL will be correlated to the measurement outcomes of the healthy controls.	During the recruitment period (up to 1 year), patients are scheduled for only 1 visit with duration of +/- 1 hour (cross-sectional design)
Development of a severity grading score for unilateral and bilateral LLL	a meeting with the international expert panel will be organized to achieve consensus regarding the measurement methods that should be performed to compile a severity score. Secondly, of all these separate measurement methods, percentiles (20, 40, 60, 80) will be calculated from the data of our study sample for this aim, serving as reference cut-off values. Consequently, 5 'severity' ranges will be presented that will correspond to a severity subscore between 0-5 for each measurement outcome. Lastly, a total severity score will be calculated	During the recruitment period (up to 1 year), patients are scheduled for only 1 visit with duration of +/- 1 hour (cross-sectional design)

Collaborators and Investigators

• Sponsor: KU Leuven
• Collaborators: Universitaire Ziekenhuizen KU Leuven; Nij Smellinghe Hospital Drachten
• Investigators: Principal Investigator: Tessa De Vrieze, Dr., KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: February 7, 2023
• First Submitted That Met QC Criteria: February 23, 2023
• First Posted (Actual): March 7, 2023

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: severity score; diagnostic set
• Additional Relevant MeSH Terms: Lymphatic Diseases; Lymphedema
• Other Study ID Numbers: s66033-aim3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No