Clinical trial NCT02609724: Effectiveness of Fluoroscopy-guided MLD for Treatment of BCRL
Official title: Effectiveness of Fluoroscopy-guided Manual Lymph Drainage (MLD) Versus Traditional MLD or Placebo MLD, as Part of Decongestive Lymphatic Therapy, for the Treatment of Breast Cancer-related Lymphoedema (BCRL): a Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Neoplasm
Lymphedema
Keywords: breast cancer
lymphedema
manual lymph drainage
near infrared fluorescence imaging
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: Agentschap voor Innovatie door Wetenschap en Technologie
First posted: 2015-11-20
Enrollment: 194
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main scientific objective of this multicentric double-blinded randomised controlled trial entails examining the effectiveness of fluoroscopy-guided MLD versus traditional MLD versus placebo MLD, applied as part of the intensive and maintenance phase of Decongestive Lymphatic Therapy, for the treatment of BCRL Secondary scientific objectives entail examining the relationship between different variables of lymphoedema at baseline

Detailed description: According to the International Society of Lymphology, lymphoedema needs to be treated with Decongestive Lymphatic Therapy (Consensus Document ISL 2013). This is a two-stage treatment programme. During the first or intensive phase, lymphoedema has to be maximally reduced. This phase consists of skin care, manual lymph drainage (MLD), multi-layer bandaging and exercise therapy. The second or maintenance phase aims to conserve and optimise the results obtained in the first phase. It consists of skin care, compression by a low-stretch elastic sleeve, exercises and lymph drainage. Skin care, multi-layer bandaging, elastic sleeve and exercises are treatment modalities that (after instructing the patient) can be performed by the patient herself. MLD has to be applied by a physical therapist and hence entails a big financial cost for the patient and the Health Care (Kärki et al 2009). The effectiveness of MLD applied during the intensive phase has been investigated by 5 randomised controlled trials, but there is conflicting evidence. So, further investigation is warranted to determine the relative benefit of MLD. The effectiveness of MLD applied during the maintenance phase has never been investigated (Devoogdt et al 2010, Oremus et al 2012, Huang et al 2013, Ezzo et al 2015).

A possible explanation why MLD is not obviously proven to be effective, is that MLD is applied in an inefficient way: during MLD, hand manoeuvres are applied on all lymph nodes and lymphatics that may be anatomically present. After axillary dissection and/ or radiotherapy (for the treatment of breast cancer), the lymphatic system is damaged: lymph nodes are removed and often fibrosis of the superficial lymphatic system occurs. As a result, rerouting of the lymphatic drainage occurs. Rerouting is patient-specific, consequently, it is possible that the traditional MLD needs be abandoned and a tailored approach needs to be established. Lymphofluoroscopy can aid to apply a more efficient MLD. During lymphofluoroscopy, a fluorescent substance is injected subcutaneously in the hand and it visualizes the transport of lymph from the hand up to the axilla and it demonstrates alternative pathways towards other lymph nodes.

A second explanation why the traditional method of MLD is not proven to be effective, is that research has shown that MLD with high pressure (vs low pressure) is more effective to improve lymph transport, as well as gliding (vs no gliding). During the new method of MLD (or fluoroscopy-guided MLD), the therapist only performs hand movements on functional lymphatics and lymph nodes. In addition, the hand movements are applied with higher pressure and lymph transport through the lymph collaterals is stimulated by applying strikes across the skin.

Therefore, the main scientific objective entails examining the effectiveness of fluoroscopy-guided MLD versus traditional MLD versus placebo MLD, applied as part of the intensive and maintenance phase of Decongestive Lymphatic Therapy, for the treatment of BCRL

Eligibility criteria: Inclusion Criteria:

* Age \>18y (since the treatment with MLD and the investigation using ICG is not dangerous for pregnant women, women with child bearing age are included)
* Women/ men with breast cancer-related lymphoedema
* Chronic lymphoedema (\>3 months present), stage I to IIb
* At least 5% difference between both arms and/ or hands, adjusted for dominance
* Written informed consent obtained

Exclusion Criteria:

* Allergy for iodine, sodiumiodine, ICG
* Increased activity of the thyroid gland; benign tumors of the thyroid gland
* Age \<18y
* Oedema of the upper limb from other causes
* Active metastasis of the cancer
* Surgery of the lymphatic system in the past (lymph node transplantation, lymphovenous shunt)
* Cannot participate during the entire study period
* Mentally or physically unable to participate in the study

Primary outcomes:
measure: Lymphoedema Volume at the Level of the Arm/ Hand
timeFrame: Primary endpoint = After 3 weeks of intensive treatment
measure: Stagnation of Fluid at Level of the Shoulder/ Trunk
timeFrame: Primary endpoint = After 3 weeks of intensive treatment
Secondary outcomes:
measure: Extracellular Fluid in the Upper Limb
timeFrame: After 3 weeks of intensive treatment, 1, 3, 6 months of maintenance treatment and 6 months of follow-up
measure: Thickness of Cutis and Subcutis of Arm and Trunk Measured With Ultrasound
timeFrame: After 3 weeks of intensive treatment and 6 months of maintenance treatment and 6 months of follow-up
measure: Problems in Functioning Related to Development of Breast Cancer-related Lymphoedema
timeFrame: After 3 weeks of intensive treatment, 1, 3, 6 months of maintenance treatment and 6 months of follow-up
measure: Elasticity of Skin and Subcutaneous Tissue of Arm and Trunk Using the SkinFibrometer
timeFrame: After 3 weeks of intensive treatment, 1, 3, 6 months of maintenance treatment and 6 months of follow-up
measure: Quality of Life Score
timeFrame: After 3 weeks of intensive treatment and 1, 3, 6 months of maintenance treatment and 6 months of follow-up
measure: Number of Episodes of Erysipelas
timeFrame: Between baseline and the end of the follow-up phase (12 months)
measure: Overall Treatment Satisfaction
timeFrame: Between baseline and the end of the follow-up phase (12 months)
measure: Manual Lymphatic Drainage (MLD)-Specific Treatment Satisfaction
timeFrame: Between baseline and the end of the follow-up phase (12 months)
measure: Local Tissue Water at the Level of the Arm and Trunk
timeFrame: After 3 weeks of intensive treatment phase, after 1, 3, 6 months of maintenance treatments and after 6 months of follow-up
measure: Thickness of the Cutis and Subcutis of the Arm and Trunk Evaluated by Palpation (Pinch Test)
timeFrame: After 3 weeks of intensive treatment, 1, 3, 6 months of maintenance treatment and 6 months of follow-up
measure: Hardness (Fibrosis) of the Skin at the Level of the Arm and Trunk Evaluated Through Palpation
timeFrame: After 3 weeks of intensive treatment, 1, 3, 6 months of maintenance treatment and 6 months of follow-up
measure: Lymphatic Architecture and Function
timeFrame: After 3 weeks of intensive treatment and 6 months of maintenance treatment
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: Antwerp University Hospital
city: Brussel
country: Belgium
facility: Centre Hospitalier Universitaire (CHU) Sint-Pieter, Lymphoedema Clinic
city: Leuven
country: Belgium
facility: University Hospitals of Leuven, lymphovenous center
Study officials:
affiliation: University of Leuven - KU Leuven and University Hospitals Leuven
name: Nele Devoogdt, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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