Effectiveness of Fluoroscopy-guided MLD for Treatment of BCRL

Overview

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

Full Title of Study: “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

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: May 2019

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

Interventions

  • Other: Information
    • During intensive phase: a leaflet with information about the lymphatic system and lymphoedema, clinical evaluation and conservative treatment of lymphoedema During maintenance phase: two informational sessions about self-management and about compression sleeves and other compression material
  • Other: Skin care
    • The skin is hydrated during the session. If wounds are present, the wound is cared.
  • Other: Compression therapy
    • During intensive phase: application of multi-layer, multi-component bandages During maintenance phase: wearing custom-made compression garment
  • Other: Fluoroscopy-guided MLD
    • Fluoroscopy-guided MLD is applied on patient-specific lymphatic system (known from lymphofluoroscopy) by applying cleaning techniques on lymph nodes, resorption techniques to stimulate resorption of lymph by lymph capillaries and gliding technique to stimulate transport of lymph through lymph collectors
  • Other: Traditional MLD
    • Traditional MLD is applied without knowledge of the patient-specific lymphatic architecture. During MLD no cream or oil is used. A pressure with the hands up to 40 mmHg is applied. Drainage is performed at the level of the jugular and occipital region and the belly (in the depth). Draining techniques are applied on the retroclavicular lymph nodes, axillary lymph nodes, humeral lymph nodes and cubital lymph nodes. At the level of the hand, arm, shoulder and trunk, hand movements are applied to stimulate lymphatic transport through the lymph collectors. The therapist’s hands perform ‘pumping-movements’ while stretching the skin.
  • Other: Placebo MLD
    • During placebo MLD a superficial massage with massage cream is performed on the patient’s contralateral arm and on the belly.

Arms, Groups and Cohorts

  • Experimental: Fluoroscopy-guided MLD
    • Information, skin care, compression therapy, exercises and fluoroscopy-guided MLD 3 weeks (15 sessions of 60 minutes) of intensive treatment 6 months (18 sessions of 60 minutes) of maintenance treatment
  • Active Comparator: Traditional MLD
    • Information, skin care, compression therapy, exercises and traditional MLD 3 weeks (15 sessions of 60 minutes) of intensive treatment 6 months (18 sessions of 60 minutes) of maintenance treatment
  • Placebo Comparator: Placebo MLD
    • Information, skin care, compression therapy, exercises and placebo MLD 3 weeks (15 sessions of 60 minutes) of intensive treatment 6 months (18 sessions of 60 minutes) of maintenance treatment

Clinical Trial Outcome Measures

Primary Measures

  • Change of lymphoedema volume of arm/ hand
    • Time Frame: After 3 weeks of intensive treatment and 6 months of maintenance treatment
  • Change of stagnation of fluid at level of shoulder/ trunk
    • Time Frame: After 3 weeks of intensive treatment and 6 months of maintenance treatment

Secondary Measures

  • Change of extracellular fluid in arm
    • Time Frame: After 3 weeks of intensive treatment and 6 months of maintenance treatment
  • Change of thickness and reflectivity of cutis and subcutis of arm/ shoulder/ trunk
    • Time Frame: After 3 weeks of intensive treatment and 6 months of maintenance treatment
  • Change of problems in functioning related to development of breast cancer-related lymphoedema
    • Time Frame: After 3 weeks of intensive treatment and 6 months of maintenance treatment
  • Change of elasticity of skin and subcutaneous tissue of arm
    • Time Frame: After 3 weeks of intensive treatment and 6 months of maintenance treatment
  • Change of lymphatic architecture and function
    • Time Frame: After 3 weeks of intensive treatment and 6 months of maintenance treatment
  • Change of venous circulation in arm/ trunk
    • Time Frame: After 3 weeks of intensive treatment and 6 months of maintenance treatment
  • Change of quality of life
    • Time Frame: After 3 weeks of intensive treatment and 6 months of maintenance treatment
  • Number of episodes of erysipelas
    • Time Frame: After 3 weeks of intensive treatment and 6 months of maintenance treatment
  • Number of responders to the treatment
    • Time Frame: After 3 weeks of intensive treatment and 6 months of maintenance treatment

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Universitaire Ziekenhuizen Leuven
  • Collaborator
    • Agentschap voor Innovatie door Wetenschap en Technologie
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Nele Devoogdt, PhD, Principal Investigator, University of Leuven – KU Leuven and University Hospitals Leuven
  • Overall Contact(s)
    • Nele Devoogdt, PhD, 0032 16 342515, nele.devoogdt@uzleuven.be

References

Huang TW, Tseng SH, Lin CC, Bai CH, Chen CS, Hung CS, Wu CH, Tam KW. Effects of manual lymphatic drainage on breast cancer-related lymphedema: a systematic review and meta-analysis of randomized controlled trials. World J Surg Oncol. 2013 Jan 24;11:15. doi: 10.1186/1477-7819-11-15. Review.

Ezzo J, Manheimer E, McNeely ML, Howell DM, Weiss R, Johansson KI, Bao T, Bily L, Tuppo CM, Williams AF, Karadibak D. Manual lymphatic drainage for lymphedema following breast cancer treatment. Cochrane Database Syst Rev. 2015 May 21;(5):CD003475. doi: 10.1002/14651858.CD003475.pub2. Review.

Devoogdt N, Christiaens MR, Geraerts I, Truijen S, Smeets A, Leunen K, Neven P, Van Kampen M. Effect of manual lymph drainage in addition to guidelines and exercise therapy on arm lymphoedema related to breast cancer: randomised controlled trial. BMJ. 2011 Sep 1;343:d5326. doi: 10.1136/bmj.d5326.

Devoogdt N, Van Kampen M, Geraerts I, Coremans T, Christiaens MR. Lymphoedema Functioning, Disability and Health questionnaire (Lymph-ICF): reliability and validity. Phys Ther. 2011 Jun;91(6):944-57. doi: 10.2522/ptj.20100087. Epub 2011 Apr 14.

Devoogdt N, Lemkens H, Geraerts I, Van Nuland I, Flour M, Coremans T, Christiaens MR, Van Kampen M. A new device to measure upper limb circumferences: validity and reliability. Int Angiol. 2010 Oct;29(5):401-7.

Devoogdt N, Pans S, De Groef A, Geraerts I, Christiaens MR, Neven P, Vergote I, Van Kampen M. Postoperative evolution of thickness and echogenicity of cutis and subcutis of patients with and without breast cancer-related lymphedema. Lymphat Res Biol. 2014 Mar;12(1):23-31. doi: 10.1089/lrb.2013.0028. Epub 2014 Feb 6.

Gebruers N, Truijen S, Engelborghs S, De Deyn PP. Volumetric evaluation of upper extremities in 250 healthy persons. Clin Physiol Funct Imaging. 2007 Jan;27(1):17-22.

Tan IC, Maus EA, Rasmussen JC, Marshall MV, Adams KE, Fife CE, Smith LA, Chan W, Sevick-Muraca EM. Assessment of lymphatic contractile function after manual lymphatic drainage using near-infrared fluorescence imaging. Arch Phys Med Rehabil. 2011 May;92(5):756-764.e1. doi: 10.1016/j.apmr.2010.12.027.

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