Breast NeoplasmEFforT-BCRLNCT02609724
Effectiveness of Fluoroscopy-guided MLD for Treatment of BCRL
A study testing Information, Skin care and Compression therapy in people with Breast Neoplasm and Lymphedema, run by Universitaire Ziekenhuizen KU Leuven at 3 sites in Belgium.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Neoplasm, Lymphedema
- What is being tested?
- Information, Skin care and Compression therapy
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 194 participants
- Where
- 3 sitesBelgium
- Study dates
- Jan 2016to Sep 2020
- Phase
- Interventional
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country.
Belgium3 sites
Antwerp University Hospital
Antwerp, 2650
Centre Hospitalier Universitaire (CHU) Sint-Pieter, Lymphoedema Clinic
Brussels, 1000
University Hospitals of Leuven, lymphovenous center
Leuven, 3000
About this study
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
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
Read the 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
- Conditions
- Breast Neoplasm, Lymphedema
- Being tested
- Information, Skin care, Compression therapy, Fluoroscopy-guided MLD, Traditional MLD
- Keywords
- breast cancer, lymphedema, manual lymph drainage, near infrared fluorescence imaging
- Medical subject headings
- Breast Neoplasms, Lymphedema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InformationOther
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
Skin careOther
The skin is hydrated during the session. If wounds are present, the wound is cared.
Compression therapyOther
During intensive phase: application of multi-layer, multi-component bandages During maintenance phase: wearing custom-made compression garment
Fluoroscopy-guided MLDOther
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
Traditional MLDOther
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.
Placebo MLDOther
During placebo MLD a superficial massage with massage cream is performed on the patient's contralateral arm and on the belly.
| Study group | Role | What they receive |
|---|---|---|
| Fluoroscopy-guided MLD | Experimental | Information, skin care, compression therapy, exercises and fluoroscopy-guided MLD 3 weeks (14 sessions of 60 minutes) of intensive treatment 6 months (18 sessions of 60 minutes) of maintenance treatment 6 months of follow-up Receives: Other: Information; Other: Skin care; Other: Compression therapy; Other: Fluoroscopy-guided MLD |
| Traditional MLD | Active comparator | Information, skin care, compression therapy, exercises and traditional MLD 3 weeks (14 sessions of 60 minutes) of intensive treatment 6 months (18 sessions of 60 minutes) of maintenance treatment 6 months of follow-up Receives: Other: Information; Other: Skin care; Other: Compression therapy; Other: Traditional MLD |
| Placebo MLD | Placebo comparator | Information, skin care, compression therapy, exercises and placebo MLD 3 weeks (14 sessions of 60 minutes) of intensive treatment 6 months (18 sessions of 60 minutes) of maintenance treatment 6 months of follow-up Receives: Other: Information; Other: Skin care; Other: Compression therapy; Other: Placebo MLD |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lymphoedema Volume at the Level of the Arm/ Hand
= the ratio at the different time points; The (inter-limb) ratio = Relative excessive lymphoedema volume of the arm/ hand = [(volume arm + volume hand affected side) / (corrected volume arm + corrected volume hand healthy side)]; Volume arm is determined by performing circumference measurements and calculating the volume with the formula of the truncated cone; Volume hand is determined by the water displacement method; The volume of the non-dominant hand/arm is on average 3.3% smaller than the dominant hand/arm, therefore is the volume of the arm at the healthy side corrected for hand dominance
Measured: Primary endpoint = After 3 weeks of intensive treatment
Stagnation of Fluid at Level of the Shoulder/ Trunk
Ratio PWC% at the different time intervals
= PWC% affected side / PWC% healthy side Measured with the MoistureMeterD compact at the level of shoulder and trunk where after a mean ratio PWC% is calculated
Measured: Primary endpoint = After 3 weeks of intensive treatment
Secondary outcomes (12)
Extracellular Fluid in the Upper Limb
L-Dex score, measured with Impedimed BIS device at the different time points Amount of extracellular fluid = represented by L-Dex score This outcome is calculated and displayed on the Impedimed BIS device, and represents the difference in the amount of extracellular fluid in the affected upper limb compared to the unaffected upper limb. Normal L-Dex scores range between -10 and +10. A score outside this range, represents lymphedema. A higher number, represents a worse score.
Measured: After 3 weeks of intensive treatment, 1, 3, 6 months of maintenance treatment and 6 months of follow-up
Thickness of Cutis and Subcutis of Arm and Trunk Measured With Ultrasound
Analyses for change in thickness of cutis + subcutis were performed:
Relative excessive thickness of the cutis+subcutis (inter-limb ratio of cutis+subcutis in mm) = Thickness of cutis+subcutis (mm) affected side / thickness of cutis+subcutis (mm) healthy side Arm: Reference points 1, 2, 3, 5, 6, 7 where after a mean ratio thickness of cutis+subcutis is calculated
Measured: After 3 weeks of intensive treatment and 6 months of maintenance treatment and 6 months of follow-up
Problems in Functioning Related to Development of Breast Cancer-related Lymphoedema
Different scores are obtained from the questionnaire. Each of the 29 questions has to be scored on a 11-point Likert scale between 0 and 10 (instead of a VAS between 0 and 100). The total score of the Lymph-ICF-UL is equal to the sum of the scores on the questions divided by the total number of answered questions and multiplied by 10. In addition, a score is determined for each of the five domains of the Lymph-ICFUL: (1) physical function, (2) mental function, (3) household activities, (4) mobility activities, and (5) life and social activities.
Thus, the total score on the Lymph-ICF-UL and the score on the five domains range between 0 and 100. The higher the score, the more problems in functioning.
Measured: After 3 weeks of intensive treatment, 1, 3, 6 months of maintenance treatment and 6 months of follow-up
Elasticity of Skin and Subcutaneous Tissue of Arm and Trunk Using the SkinFibrometer
Induration force is presented in Newton (N) by the device. Relative difference in skin elasticity (induration force inter-limb ratio) = Skin elasticity affected side / skin elasticity healthy side Arm: Reference points 1, 2, 3, 5, 6, 7 where after a mean induration ratio is calculated
Measured: After 3 weeks of intensive treatment, 1, 3, 6 months of maintenance treatment and 6 months of follow-up
Quality of Life Score
At the end of each assessment, subjects are asked to fill in the questionnaire individually Questionnaire counts 16 + 1 questions, which relate to the following 5 domains: physical symptoms; physical wellbeing, psychological symptoms; existential wellbeing and support A Likert scale with 11 possibilities (0-10) is used for the 16 questions and part D is an open question Each question corresponds to a score between 0 (very bad) and 10 (excellent); a total score and 5 different domain scores are calculated (each between 0 and 10) A lower score indicates a lower Quality of Life
Measured: After 3 weeks of intensive treatment and 1, 3, 6 months of maintenance treatment and 6 months of follow-up
Number of Episodes of Erysipelas
At each clinical evaluation, it was asked to the patient if they had had an episode of erysipelas (which is an infection) between today and the previous evaluation.
The numbers of episodes were counted, and the causes of this episode of erysipelas were described. The numbers of episodes were compared between the groups.
Measured: Between baseline and the end of the follow-up phase (12 months)
Overall Treatment Satisfaction
The number patients presented as a percentage that indicated that their complaints have been slightly (3), much (2) or very much improved (1) during 12 months of time
Measured: Between baseline and the end of the follow-up phase (12 months)
Manual Lymphatic Drainage (MLD)-Specific Treatment Satisfaction
The mean rating of the perceived effect of the manual lymph drainage (MLD) that patients received during the study (between 0-10). The higher the score, the higher the satisfaction about the effect of the manual lymph drainage received.
Measured: Between baseline and the end of the follow-up phase (12 months)
Local Tissue Water at the Level of the Arm and Trunk
Ratio PWC% at the different time intervals
= PWC% affected side / PWC% healthy side Measured with the MoistureMeterD compact at different measurement points where after a mean ratio PWC% is calculated Arm: Reference points 1, 2, 3, 5, 6, 7 where after a mean ratio PWC% is calculated
Measured: After 3 weeks of intensive treatment phase, after 1, 3, 6 months of maintenance treatments and after 6 months of follow-up
Thickness of the Cutis and Subcutis of the Arm and Trunk Evaluated by Palpation (Pinch Test)
In total, six reference points (located at the hand (1 reference point) and arm (5 reference points)) are being evaluated and scored (0 or 1) A reference point is scored with 1 in case the skin fold thickness at the affected side is increased compared to the reference point at the non-affected side The final outcome for the arm score is the (cumulated) total score of six reference points 1, 2, 3, 5, 6, 7 (range 0-6), a higher score indicates more presence of thickened skin
Measured: After 3 weeks of intensive treatment, 1, 3, 6 months of maintenance treatment and 6 months of follow-up
Hardness (Fibrosis) of the Skin at the Level of the Arm and Trunk Evaluated Through Palpation
In total, six reference points (located at the hand (1 reference point) and arm (5 reference points)) are being evaluated and scored (0 or 1) A reference point is scored with 1 in case fibrosis of the skin is present The final outcome for the arm score is the (cumulated) total score of six reference points 1, 2, 3, 5, 6, 7 (range 0-6), a higher score indicates more presence of fibrosis
Measured: After 3 weeks of intensive treatment, 1, 3, 6 months of maintenance treatment and 6 months of follow-up
Lymphatic Architecture and Function
- Total dermal backflow score (0-39). The higher the score, the more dermal backflow is present
- Amount of efferent lymphatics leaving dermal backflow areas
- Presence of visible lymph nodes after the break
Raw data is currently still being analyzed in order to be able to report on the described outcome measures. At present (March 2022) these analyses are not yet performed. Therefore these results will be reported later on this year (anticipated date: July 2022).
Measured: After 3 weeks of intensive treatment and 6 months of maintenance treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2015 (estimated)
- Study startJan 2016
- Primary completionMar 2020
- Study completionSep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Breast NeoplasmStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 194 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Collaborators
- Agentschap voor Innovatie door Wetenschap en Technologie
- Responsible party
- Sponsor
- Investigators
- Nele Devoogdt, PhD, Principal investigator, University of Leuven - KU Leuven and University Hospitals Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02609724
- Sponsor's protocol ID
- IWT150178
- Acronym
- EFforT-BCRL
- Status last verified
- Mar 2022
- First submitted
- 17 Nov 2015
- Last updated
- 17 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 23347817Ezzo 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;2015(5):CD003475. doi: 10.1002/14651858.CD003475.pub2.
PubMed 25994425Devoogdt 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.
PubMed 21885537Devoogdt 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.
PubMed 21493748Devoogdt 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.
PubMed 20924341Devoogdt 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.
PubMed 24502300Gebruers 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. doi: 10.1111/j.1475-097X.2007.00708.x.
PubMed 17204033Tan 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.
PubMed 21530723De Vrieze T, Gebruers N, Nevelsteen I, Thomis S, De Groef A, Tjalma WAA, Belgrado JP, Vandermeeren L, Monten C, Hanssens M, Asnong A, Dams L, Van der Gucht E, Heroes AK, Devoogdt N. Does Manual Lymphatic Drainage Add Value in Reducing Suprafascial Fluid Accumulation and Skin Elasticity in Patients With Breast Cancer-Related Lymphedema? Phys Ther. 2022 Dec 6;102(12):pzac137. doi: 10.1093/ptj/pzac137.
PubMed 36209432De Vrieze T, Gebruers N, Nevelsteen I, Fieuws S, Thomis S, De Groef A, Tjalma WA, Belgrado JP, Vandermeeren L, Monten C, Hanssens M, Devoogdt N. Manual lymphatic drainage with or without fluoroscopy guidance did not substantially improve the effect of decongestive lymphatic therapy in people with breast cancer-related lymphoedema (EFforT-BCRL trial): a multicentre randomised trial. J Physiother. 2022 Apr;68(2):110-122. doi: 10.1016/j.jphys.2022.03.010. Epub 2022 Apr 12.
PubMed 35428594Thomis S, Helberg M, Kleiman J, Vrieze T, Heroes AK, Fourneau I, Devoogdt N. The Interrater Reliability of the Scoring of the Lymphatic Architecture and Transport Through Near-InfraRed Fluorescence Lymphatic Imaging in Patients with Breast Cancer-Related Lymphedema. Lymphat Res Biol. 2022 Apr;20(2):133-143. doi: 10.1089/lrb.2020.0105. Epub 2021 Jun 2.
PubMed 34077678De Vrieze T, Gebruers N, Nevelsteen I, Tjalma WAA, Thomis S, De Groef A, Dams L, Haenen V, Devoogdt N. Breast cancer-related lymphedema and its treatment: how big is the financial impact? Support Care Cancer. 2021 Jul;29(7):3801-3813. doi: 10.1007/s00520-020-05890-3. Epub 2020 Nov 24.
PubMed 33236211Thomis S, Dams L, Fourneau I, De Vrieze T, Nevelsteen I, Neven P, Gebruers N, Devoogdt N. Correlation Between Clinical Assessment and Lymphofluoroscopy in Patients with Breast Cancer-Related Lymphedema: A Study of Concurrent Validity. Lymphat Res Biol. 2020 Dec;18(6):539-548. doi: 10.1089/lrb.2019.0090. Epub 2020 Mar 25.
PubMed 32208953De Vrieze T, Gebruers N, Nevelsteen I, Tjalma WAA, Thomis S, De Groef A, Dams L, Van der Gucht E, Devoogdt N. Physical activity level and age contribute to functioning problems in patients with breast cancer-related lymphedema: a multicentre cross-sectional study. Support Care Cancer. 2020 Dec;28(12):5717-5731. doi: 10.1007/s00520-020-05375-3. Epub 2020 Mar 19.
PubMed 32193692De Vrieze T, Frippiat J, Deltombe T, Gebruers N, Tjalma WAA, Nevelsteen I, Thomis S, Vandermeeren L, Belgrado JP, De Groef A, Devoogdt N. Cross-cultural validation of the French version of the Lymphedema Functioning, Disability and Health Questionnaire for Upper Limb Lymphedema (Lymph-ICF-UL). Disabil Rehabil. 2021 Sep;43(19):2797-2804. doi: 10.1080/09638288.2020.1716271. Epub 2020 Jan 28.
PubMed 31990592