Lower Extremity LymphedemaNCT06750679
Non-inferiority of Compression Bandage Alone in Lower Extremity Lymphedema Management
A study testing Compression bandage and Manual lymphatic drainage added to compression in people with Lower Extremity Lymphedema, run by Abant Izzet Baysal University at 1 site in Turkey (Türkiye).
Trial summary
Lymphedema is much more than a disease with edema. Impaired lymphatic drainage triggers adipose tissue deposition and fibrosis. Fibrosis causes lymphatic vessel dysfunction. Therefore, treatment of fibrosis is important. The gold standard of treatment for lymphedema is complex decongestive physiotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lower Extremity Lymphedema
- What is being tested?
- Compression bandage and Manual lymphatic drainage added to compression
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 1 Sep 2024to 1 Apr 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- According to the criteria of the International Society of Lymphology Stage 2 and 3 lower extremity LE to volunteer to participate in the study
- To be between the ages of 18-80
- LE involving the entire lower extremity
Who cannot join
- Acute deep vein thrombosis
- Acute infection
- Peripheral arterial disease in the lower extremity
- To have systemic diseases that may cause edema other than LE (renal failure, liver failure, heart failure, etc.)
- Chronic venous insufficiency
- Allergy to materials used in treatment
Show all 11Show fewer
- Mental/cognitive problems that will affect cooperation
- Loss of sensation
- Presence of scleroderma in the treatment area
- Active cancer
- Radiogenic fibrosis in the treatment area
Trial locations and contacts
1 site in 1 country.
Turkey (Türkiye)1 site
Bolu Abant Izzet Baysal University
Bolu, Merkez, 14030
About this study
Official title: MANUAL LYMPH DRAINAGE IN LOWER EXTREMITY LYMPHEDEMA MANAGEMENT: AN ESSENTIAL COMPONENT OR AN OPTIONAL EXTRA ? - A SINGLE-BLIND, RANDOMIZED NON-INFERIORITY TRIAL
Lymphedema is much more than a disease with edema. Impaired lymphatic drainage triggers adipose tissue deposition and fibrosis. Fibrosis causes lymphatic vessel dysfunction. Therefore, treatment of fibrosis is important. The gold standard of treatment for lymphedema is complex decongestive physiotherapy. In this treatment method consisting of two phases and four components in each phase, each component has its own effect. Compression is the main component of these components in terms of edema reduction. The effect of manual lymph drainage, another component, on edema and fibrosis is contradictory. Although there are studies evaluating fibrosis in lower extremity lymphedema in the literature, there is no study evaluating the effect of treatment on fibrosis and comparing two different methods evaluating fibrosis.
Research question: What is the effect of manual lymph drainage in addition to compression therapy on fibrosis, edema, skin and subcutaneous tissue thickness, and quality of life.
Read more
The primary aim of this study was to evaluate the effect of manual lymph drainage applied as an adjunct to compression therapy on fibrosis in individuals with lower extremity lymphedema. The secondary aim of the study was to evaluate the effect of manual lymph drainage in addition to compression therapy on skin and subcutaneous tissue thickness, edema and quality of life.
Patients with lower extremity lymphedema will be randomly allocated to the compression group and manual lymph drainage + compression group. Fibrosis in the tissues of the individuals will be evaluated by ultrasound and SkinFibrometer device, skin and subcutaneous tissue thickness will be evaluated by ultrasound, edema perimeter measurement will be converted to volume, and quality of life will be evaluated by Lymphedema Quality of Life Questionnaire-Lower Extremity before and after treatment. Individuals will be randomized to either 20 sessions of compression bandage or 20 sessions of compression bandage with manual lymph drainage. Both groups will include skin care and exercise components of complex decongestive physiotherapy.
This study will provide important data on whether manual lymph drainage is clinically necessary in the treatment of lower limb lymphedema.
Read the detailed description
Lower extremity lymphedema (LE) is a chronic disease characterized by the accumulation of protein-rich fluid in the interstitial space and inflammation. It is classified as primary and secondary lymphedema. Primary LE is caused by developmental defects of the lymphatic system, whereas secondary LE is caused by subsequent damage to the lymphatic system. The biggest cause of secondary LE in western countries is cancer surgery.
Lower extremity LE is not a disease characterized only by edema. As the disease progresses, adipose tissue increases and fibrosis is observed. Fibrosis is defined as excessive accumulation of extracellular matrix products. Fibrosis is a well-known cause of organ dysfunction in many systems, including the liver, kidney, heart, and skin. This condition also occurs in limb LL and is a characteristic pathological change seen in LL. The increase in adipose tissue and fibrosis triggered by the presence of lymph fluid leads to increased skin and subcutaneous tissue thickness. These changes increase as the duration and stage of the disease progress.
Inflammation due to impaired lymph drainage triggers the fibrosis process. Histological and immunohistochemical specimens from clinical and experimental skin tissues of patients with LE reveal an increase in collagen fibers in edematous skin due to fibrosis. Fibrosis in LE is not limited to the skin but has also been detected in subcutaneous tissue, including adipose tissue. It has been reported that adipocytes in adipose tissue with LE have hypertrophic changes and larger adipose tissue lobules, and these lobules are surrounded by thick collagen fibers and interstitial lymphatic fluid. It has been reported that collagen accumulation in subcutaneous fat was observed in mouse models of LE. This leads to hardening of the tissue , resulting in non-depressed edema. Fibrosis in the tissue causes lymphatic vessel dysfunction and reduces lymphatic capacity, leading to worsening of LE. It has been reported that fibrotic changes in lymphedema can be partially reversed with complex decongestive physiotherapy (CDF). CDF is a conservative treatment method accepted as the gold standard in the treatment of LE. It consists of two phases: discharge and protection. While the unloading phase aims to reduce limb volume, the preservation phase aims to maintain the reduced volume. The unloading phase consists of 4 main components: manual lymph drainage (MLD), skin care, compression, and exercise. In the protection phase, compression bandages are replaced by compression garments, and manual lymph drainage is replaced by self/simple lymph drainage. The drainage phase lasts at least 2-4 weeks, and the protection phase lasts for life Each treatment component has a unique mechanism of action in the treatment of lymphedema. MLD is a gentle massage technique that aims to move the skin and connective tissue, thus stretching the anchor filaments connected to the lymphatic capillaries and opening the lymphatic capillaries without causing hyperemia. There are different holding techniques. MLD is thought to increase the transport rate of lymphatic fluid, develop new pathways for lymphatic drainage from edematous areas to adjacent non-edematous areas, remove protein deposits from the tissue, and break down fibrotic tissue. Compression is to create more tissue pressure during contractions by resisting muscle activity. This is the strongest stimulation for lymph drainage. Compression also prevents fluid accumulation in the tissue by reducing capillary filtration. It allows resorption of fluid in the interstitial space. It displaces fluid to non-compressed areas where drainage is normal. Compression is also thought to be effective in the destruction of fibrosclerotic tissue.
In the literature, the effect of MLD and compression applications on edema has been frequently evaluated, and the effectiveness of compression bandaging has been shown, although the effect of MLD on edema reduction is contradictory. Nevertheless, it has been suggested that MLD may also be effective in fibrotic tissue. However, although there are evaluation studies showing fibrosis in tissue with LE, there are no randomized controlled trials showing the effect of MLD and compression on fibrotic tissue in lower extremity LE. Similarly, there are no studies comparing the effect of lymphedema treatments on fibrosis using two different assessment methods. The primary aim of this study was to evaluate the effect of MLD applied as an adjunct to compression therapy on fibrosis in individuals with lower extremity LE. The secondary aim of the study was to evaluate the effect of MLD applied in addition to compression bandage on skin and subcutaneous tissue thickness, edema, and quality of life.
- Conditions
- Lower Extremity Lymphedema
- Being tested
- Compression bandage, Manual lymphatic drainage added to compression
- Keywords
- lower extremity lymphedema, fibrosis, manual lymphatic drainage, Complex decongestive physiotherapy, Quality of life
- Medical subject headings
- Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Compression bandageOther
A multicomponent inelastic compression bandage will be applied to the patient. Skin care and simple exercises will be added to intervention
Manual lymphatic drainage added to compressionOther
Manual lymphatic drainage will be added to multicomponent inelastik compression bandage, skin care and simple exercises
| Study group | Role | What they receive |
|---|---|---|
| Compression Group | Active comparator | In compression therapy, multicomponent inelastic compression bandages bandages will be applied (Misra et al., 2023). The individual will be fitted with a stockinet beforehand. Fingers will be bandaged. Then, the extremity will be cylindricalized with a cotton roller or sponge. Subsequently, the foot and ankle will be bandaged using a 6 cm short-stretch bandage. An 8 cm short-stretch bandage will be applied starting from the foot and progressing upward above the ankle. A 10 cm short-stretch bandage will then be applied, beginning at the ankle and wrapping upward. The next bandages will be wrapped upwards starting from the places where the pressure is low. The compression bandage will remain on the patient's leg for approximately 23 hours. When the individual arrives the next day, the bandage will be removed and reapplied. The application time of the inelastic bandage is approximately 20-30 minutes. Compression therapy will be applied 5 days a week for 4 weeks (20 sessions) Receives: Other: Manual lymphatic drainage added to compression |
| Compression+MLD Group | Experimental | Participants in the group receiving MLD in addition to compression therapy will undergo a 30-40-minute MLD session to facilitate the entry of interstitial fluid into lymphatic capillaries and enhance lymph propulsion (Misra et al., 2023). The MLD will be performed with gentle pressure of approximately 30-40 mmHg, ensuring the skin and connective tissue move together without sliding on the skin.
After the MLD session, a multilayer bandaging will be applied to the extremity, which the patient will wear for approximately 23 hours. The bandage will be removed and reapplied during the patient's visit the following day.
The combined therapy of compression and MLD will be administered five days a week for four weeks (20 sessions in total). Each session will last approximately 50-70 minutes. Receives: Other: Compression bandage |
What is being measured
The primary outcome is the main question the study is designed to answer.
Edema Assessment
Edema will be assessed by circumference measurements with the patient in a supine position. Measurements will start 10 cm from the heel. Along the lateral aspect of the leg, marks will be made at 8 cm intervals, and circumference measurements will be taken at these points along the extremity.
Using a non-elastic tape measure 1 cm in width, measurements will be conducted without compressing the tissue and ensuring the ends of the tape do not overlap. Measurements will be recorded in centimeters. This process will be performed bilaterally.
The recorded circumferences will then be converted into volume using the truncated cone formula, as extremities are considered geometrically as truncated cones for this calculation.
Measured: Baseline, four week later
Secondary outcomes (2)
Assessment of Skin and Subcutaneous Tissue Thickness
The evaluation of skin and subcutaneous tissue thickness will be performed by a specialized radiologist using a LOGIQ ultrasound system (GE Healthcare, USA) equipped with a 6-15 MHz linear probe. Measurements will be conducted with the individual in a supine position. To optimize the passage of ultrasound waves, ultrasound gel will be applied between the probe and the skin. The ultrasound probe will be positioned perpendicularly to the skin, and brightness mode (B-mode) images will be obtained without applying additional compression to the skin. For skin thickness, the measurement will include the distance between two fine echogenic lines encompassing the hypoechoic dermis, as described comprehensively in previous studies, and will be recorded in millimeters. The subcutaneous distance will be measured as the distance in millimeters between the posterior echogenic line of the dermis and the anterior echogenic line of the muscular fascia
Measured: Baseline and four week later
Assessment of Fibrosis Using the SkinFibroMeter
The patient will lie in a supine position on a treatment bed with the lower extremities relaxed. The SkinFibroMeter probe will be briefly (0.5 seconds) pressed perpendicularly against the skin. Each stiffness value will be calculated as the average of five consecutive successful measurements at the same site. If the applied force or measurement duration is incorrect, a 'USER ERROR' message will be displayed, and the measurements will be repeated.
Fibrosis will be measured at 17 points on each lower extremity. Specific landmarks will be identified, including 5 cm above the joint of the second toe, 5 cm above the lateral malleolus, 10 cm below the inferior border of the patella, and 10 cm and 20 cm above the superior border of the patella. On the thigh and calf, medial, lateral, posterior, and anterior midline points corresponding to the same circumferential level as these landmarks will also be marked
Measured: Baseline and four week later
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2024
- Study start1 Sep 2024
- Primary completion1 Mar 2026
- Study completion1 Apr 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (27)Papers the sponsor has linked to this study.
- Other trials for Lower Extremity LymphedemaStudies of the same condition, open and under way.
- More trials run by Abant Izzet Baysal UniversityThe 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
- Model description
- Non inferiority study
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abant Izzet Baysal University
- Sponsor type
- University, hospital or other
- Collaborators
- The Scientific and Technological Research Council of Turkey
- Responsible party
- Principal investigator, Elif Duygu, Abant Izzet Baysal University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06750679
- Sponsor's protocol ID
- BAIBU-FTR-ED-004
- Status last verified
- Apr 2026
- First submitted
- 20 Dec 2024
- Last updated
- 28 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Zampell JC, Aschen S, Weitman ES, Yan A, Elhadad S, De Brot Andrade M, Mehrara BJ. Regulation of adipogenesis by lymphatic fluid stasis: part I. Adipogenesis, fibrosis, and inflammation. Plast Reconstr Surg. 2012 Apr;129(4):825-834. doi: 10.1097/PRS.0b013e3182450b2d.
PubMed 22456354Yamamoto T, Yamamoto N, Hayashi N, Hayashi A, Koshima I. Practicality of the Lower Extremity Lymphedema Index: Lymphedema Index Versus Volumetry-Based Evaluations for Body-Type-Corrected Lower Extremity Volume Evaluation. Ann Plast Surg. 2016 Jan;77(1):115-8. doi: 10.1097/SAP.0000000000000362.
PubMed 26835820Tashiro K, Feng J, Wu SH, Mashiko T, Kanayama K, Narushima M, Uda H, Miyamoto S, Koshima I, Yoshimura K. Pathological changes of adipose tissue in secondary lymphoedema. Br J Dermatol. 2017 Jul;177(1):158-167. doi: 10.1111/bjd.15238. Epub 2017 Apr 2.
PubMed 28000916Szuba A, Rockson SG. Lymphedema: classification, diagnosis and therapy. Vasc Med. 1998;3(2):145-56. doi: 10.1177/1358836X9800300209.
PubMed 9796078Szolnoky G, Dobozy A, Kemeny L. Towards an effective management of chronic lymphedema. Clin Dermatol. 2014 Sep-Oct;32(5):685-91. doi: 10.1016/j.clindermatol.2014.04.017.
PubMed 25160111Suehiro K, Morikage N, Murakami M, Yamashita O, Samura M, Hamano K. Significance of ultrasound examination of skin and subcutaneous tissue in secondary lower extremity lymphedema. Ann Vasc Dis. 2013;6(2):180-8. doi: 10.3400/avd.oa.12.00102. Epub 2013 May 10.
PubMed 23825499Reed JL, Pipe AL. The talk test: a useful tool for prescribing and monitoring exercise intensity. Curr Opin Cardiol. 2014 Sep;29(5):475-80. doi: 10.1097/HCO.0000000000000097.
PubMed 25010379Mosti G, Cavezzi A. Compression therapy in lymphedema: Between past and recent scientific data. Phlebology. 2019 Sep;34(8):515-522. doi: 10.1177/0268355518824524. Epub 2019 Jan 9. No abstract available.
PubMed 30626269Lim CY, Seo HG, Kim K, Chung SG, Seo KS. Measurement of lymphedema using ultrasonography with the compression method. Lymphology. 2011 Jun;44(2):72-81.
PubMed 21949976Li CY, Kataru RP, Mehrara BJ. Histopathologic Features of Lymphedema: A Molecular Review. Int J Mol Sci. 2020 Apr 6;21(7):2546. doi: 10.3390/ijms21072546.
PubMed 32268536Lee DG, Lee S, Kim KT. Computed Tomography-Based Quantitative Analysis of Fibrotic Changes in Skin and Subcutaneous Tissue in Lower Extremity Lymphedema Following Gynecologic Cancer Surgery. Lymphat Res Biol. 2022 Oct;20(5):488-495. doi: 10.1089/lrb.2021.0069. Epub 2022 Jan 10.
PubMed 35012367Leduc O, Leduc A, Bourgeois P, Belgrado JP. The physical treatment of upper limb edema. Cancer. 1998 Dec 15;83(12 Suppl American):2835-9. doi: 10.1002/(sici)1097-0142(19981215)83:12b+3.0.co;2-v.
PubMed 9874408Executive Committee. The Diagnosis and Treatment of Peripheral Lymphedema: 2016 Consensus Document of the International Society of Lymphology. Lymphology. 2016 Dec;49(4):170-84.
PubMed 29908550Brorson H. From lymph to fat: liposuction as a treatment for complete reduction of lymphedema. Int J Low Extrem Wounds. 2012 Mar;11(1):10-9. doi: 10.1177/1534734612438550. Epub 2012 Feb 23.
PubMed 22363050Bernas M, Thiadens SRJ, Stewart P, Granzow J. Secondary lymphedema from cancer therapy. Clin Exp Metastasis. 2022 Feb;39(1):239-247. doi: 10.1007/s10585-021-10096-w. Epub 2021 May 5.
PubMed 33950413
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MANUAL LYMPH DRAINAGE IN LOWER EXTREMITY LYMPHEDEMA MANAGEMENT: AN ESSENTIAL COMPONENT OR AN OPTIONAL EXTRA ? - A SINGLE-BLIND, RANDOMIZED NON-INFERIORITY TRIAL
- ClinicalTrials.gov ID
- NCT06750679
- Acronym / sponsor ID
- BAIBU-FTR-ED-004
- Conditions
- Lower Extremity Lymphedema
- Keywords
- lower extremity lymphedema, fibrosis, manual lymphatic drainage, Complex decongestive physiotherapy, Quality of life
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Abant Izzet Baysal UniversityUniversity, hospital or other
- Collaborators
- The Scientific and Technological Research Council of Turkey
- Study start
- 1 Sep 2024 (actual)
- Primary completion
- 1 Mar 2026 (actual)
- Study completion
- 1 Apr 2026 (actual)
- First posted
- 27 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Lymphedema is much more than a disease with edema. Impaired lymphatic drainage triggers adipose tissue deposition and fibrosis. Fibrosis causes lymphatic vessel dysfunction. Therefore, treatment of fibrosis is important. The gold standard of treatment for lymphedema is complex decongestive physiotherapy. In this treatment method consisting of two phases and four components in each phase, each component has its own effect. Compression is the main component of these components in terms of edema reduction. The effect of manual lymph drainage, another component, on edema and fibrosis is contradictory. Although there are studies evaluating fibrosis in lower extremity lymphedema in the literature, there is no study evaluating the effect of treatment on fibrosis and comparing two different methods evaluating fibrosis.
Research question: What is the effect of manual lymph drainage in addition to compression therapy on fibrosis, edema, skin and subcutaneous tissue thickness, and quality of life.
The primary aim of this study was to evaluate the effect of manual lymph drainage applied as an adjunct to compression therapy on fibrosis in individuals with lower extremity lymphedema. The secondary aim of the study was to evaluate the effect of manual lymph drainage in addition to compression therapy on skin and subcutaneous tissue thickness, edema and quality of life.
Patients with lower extremity lymphedema will be randomly allocated to the compression group and manual lymph drainage + compression group. Fibrosis in the tissues of the individuals will be evaluated by ultrasound and SkinFibrometer device, skin and subcutaneous tissue thickness will be evaluated by ultrasound, edema perimeter measurement will be converted to volume, and quality of life will be evaluated by Lymphedema Quality of Life Questionnaire-Lower Extremity before and after treatment. Individuals will be randomized to either 20 sessions of compression bandage or 20 sessions of compression bandage with manual lymph drainage. Both groups will include skin care and exercise components of complex decongestive physiotherapy.
This study will provide important data on whether manual lymph drainage is clinically necessary in the treatment of lower limb lymphedema.
Detailed description
Lower extremity lymphedema (LE) is a chronic disease characterized by the accumulation of protein-rich fluid in the interstitial space and inflammation. It is classified as primary and secondary lymphedema. Primary LE is caused by developmental defects of the lymphatic system, whereas secondary LE is caused by subsequent damage to the lymphatic system. The biggest cause of secondary LE in western countries is cancer surgery.
Lower extremity LE is not a disease characterized only by edema. As the disease progresses, adipose tissue increases and fibrosis is observed. Fibrosis is defined as excessive accumulation of extracellular matrix products. Fibrosis is a well-known cause of organ dysfunction in many systems, including the liver, kidney, heart, and skin. This condition also occurs in limb LL and is a characteristic pathological change seen in LL. The increase in adipose tissue and fibrosis triggered by the presence of lymph fluid leads to increased skin and subcutaneous tissue thickness. These changes increase as the duration and stage of the disease progress.
Inflammation due to impaired lymph drainage triggers the fibrosis process. Histological and immunohistochemical specimens from clinical and experimental skin tissues of patients with LE reveal an increase in collagen fibers in edematous skin due to fibrosis. Fibrosis in LE is not limited to the skin but has also been detected in subcutaneous tissue, including adipose tissue. It has been reported that adipocytes in adipose tissue with LE have hypertrophic changes and larger adipose tissue lobules, and these lobules are surrounded by thick collagen fibers and interstitial lymphatic fluid. It has been reported that collagen accumulation in subcutaneous fat was observed in mouse models of LE. This leads to hardening of the tissue , resulting in non-depressed edema. Fibrosis in the tissue causes lymphatic vessel dysfunction and reduces lymphatic capacity, leading to worsening of LE. It has been reported that fibrotic changes in lymphedema can be partially reversed with complex decongestive physiotherapy (CDF). CDF is a conservative treatment method accepted as the gold standard in the treatment of LE. It consists of two phases: discharge and protection. While the unloading phase aims to reduce limb volume, the preservation phase aims to maintain the reduced volume. The unloading phase consists of 4 main components: manual lymph drainage (MLD), skin care, compression, and exercise. In the protection phase, compression bandages are replaced by compression garments, and manual lymph drainage is replaced by self/simple lymph drainage. The drainage phase lasts at least 2-4 weeks, and the protection phase lasts for life Each treatment component has a unique mechanism of action in the treatment of lymphedema. MLD is a gentle massage technique that aims to move the skin and connective tissue, thus stretching the anchor filaments connected to the lymphatic capillaries and opening the lymphatic capillaries without causing hyperemia. There are different holding techniques. MLD is thought to increase the transport rate of lymphatic fluid, develop new pathways for lymphatic drainage from edematous areas to adjacent non-edematous areas, remove protein deposits from the tissue, and break down fibrotic tissue. Compression is to create more tissue pressure during contractions by resisting muscle activity. This is the strongest stimulation for lymph drainage. Compression also prevents fluid accumulation in the tissue by reducing capillary filtration. It allows resorption of fluid in the interstitial space. It displaces fluid to non-compressed areas where drainage is normal. Compression is also thought to be effective in the destruction of fibrosclerotic tissue.
In the literature, the effect of MLD and compression applications on edema has been frequently evaluated, and the effectiveness of compression bandaging has been shown, although the effect of MLD on edema reduction is contradictory. Nevertheless, it has been suggested that MLD may also be effective in fibrotic tissue. However, although there are evaluation studies showing fibrosis in tissue with LE, there are no randomized controlled trials showing the effect of MLD and compression on fibrotic tissue in lower extremity LE. Similarly, there are no studies comparing the effect of lymphedema treatments on fibrosis using two different assessment methods. The primary aim of this study was to evaluate the effect of MLD applied as an adjunct to compression therapy on fibrosis in individuals with lower extremity LE. The secondary aim of the study was to evaluate the effect of MLD applied in addition to compression bandage on skin and subcutaneous tissue thickness, edema, and quality of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Non inferiority study
| Arm | Type | Receives |
|---|---|---|
| Compression Group | Active comparator | Other: Manual lymphatic drainage added to compressionIn compression therapy, multicomponent inelastic compression bandages bandages will be applied (Misra et al., 2023). The individual will be fitted with a stockinet beforehand. Fingers will be bandaged. Then, the extremity will be cylindricalized with a cotton roller or sponge. Subsequently, the foot and ankle will be bandaged using a 6 cm short-stretch bandage. An 8 cm short-stretch bandage will be applied starting from the foot and progressing upward above the ankle. A 10 cm short-stretch bandage will then be applied, beginning at the ankle and wrapping upward. The next bandages will be wrapped upwards starting from the places where the pressure is low. The compression bandage will remain on the patient's leg for approximately 23 hours. When the individual arrives the next day, the bandage will be removed and reapplied. The application time of the inelastic bandage is approximately 20-30 minutes. Compression therapy will be applied 5 days a week for 4 weeks (20 sessions) |
| Compression+MLD Group | Experimental | Other: Compression bandageParticipants in the group receiving MLD in addition to compression therapy will undergo a 30-40-minute MLD session to facilitate the entry of interstitial fluid into lymphatic capillaries and enhance lymph propulsion (Misra et al., 2023). The MLD will be performed with gentle pressure of approximately 30-40 mmHg, ensuring the skin and connective tissue move together without sliding on the skin. After the MLD session, a multilayer bandaging will be applied to the extremity, which the patient will wear for approximately 23 hours. The bandage will be removed and reapplied during the patient's visit the following day. The combined therapy of compression and MLD will be administered five days a week for four weeks (20 sessions in total). Each session will last approximately 50-70 minutes. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- According to the criteria of the International Society of Lymphology Stage 2 and 3 lower extremity LE to volunteer to participate in the study
- To be between the ages of 18-80
- LE involving the entire lower extremity
Key exclusion criteria (11 listed)
- Acute deep vein thrombosis
- Acute infection
- Peripheral arterial disease in the lower extremity
- To have systemic diseases that may cause edema other than LE (renal failure, liver failure, heart failure, etc.)
- Chronic venous insufficiency
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Compression bandageA multicomponent inelastic compression bandage will be applied to the patient. Skin care and simple exercises will be added to intervention | Other | Compression+MLD Group |
| Manual lymphatic drainage added to compressionManual lymphatic drainage will be added to multicomponent inelastik compression bandage, skin care and simple exercises | Other | Compression Group |
Primary outcome
Edema Assessment
Time frame: Baseline, four week later
Edema will be assessed by circumference measurements with the patient in a supine position. Measurements will start 10 cm from the heel. Along the lateral aspect of the leg, marks will be made at 8 cm intervals, and circumference measurements will be taken at these points along the extremity. Using a non-elastic tape measure 1 cm in width, measurements will be conducted without compressing the tissue and ensuring the ends of the tape do not overlap. Measurements will be recorded in centimeters. This process will be performed bilaterally. The recorded circumferences will then be converted into volume using the truncated cone formula, as extremities are considered geometrically as truncated cones for this calculation.
2 secondary outcomes
Assessment of Skin and Subcutaneous Tissue Thickness
Time frame: Baseline and four week later
Assessment of Fibrosis Using the SkinFibroMeter
Time frame: Baseline and four week later
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2026.
- Background: PubMed 22456354Zampell JC, Aschen S, Weitman ES, Yan A, Elhadad S, De Brot Andrade M, Mehrara BJ. Regulation of adipogenesis by lymphatic fluid stasis: part I. Adipogenesis, fibrosis, and inflammation. Plast Reconstr Surg. 2012 Apr;129(4):825-834. doi: 10.1097/PRS.0b013e3182450b2d.
- Background: PubMed 26835820Yamamoto T, Yamamoto N, Hayashi N, Hayashi A, Koshima I. Practicality of the Lower Extremity Lymphedema Index: Lymphedema Index Versus Volumetry-Based Evaluations for Body-Type-Corrected Lower Extremity Volume Evaluation. Ann Plast Surg. 2016 Jan;77(1):115-8. doi: 10.1097/SAP.0000000000000362.
- Background: PubMed 28000916Tashiro K, Feng J, Wu SH, Mashiko T, Kanayama K, Narushima M, Uda H, Miyamoto S, Koshima I, Yoshimura K. Pathological changes of adipose tissue in secondary lymphoedema. Br J Dermatol. 2017 Jul;177(1):158-167. doi: 10.1111/bjd.15238. Epub 2017 Apr 2.
- Background: PubMed 9796078Szuba A, Rockson SG. Lymphedema: classification, diagnosis and therapy. Vasc Med. 1998;3(2):145-56. doi: 10.1177/1358836X9800300209.
- Background: PubMed 25160111Szolnoky G, Dobozy A, Kemeny L. Towards an effective management of chronic lymphedema. Clin Dermatol. 2014 Sep-Oct;32(5):685-91. doi: 10.1016/j.clindermatol.2014.04.017.
- Background: PubMed 23825499Suehiro K, Morikage N, Murakami M, Yamashita O, Samura M, Hamano K. Significance of ultrasound examination of skin and subcutaneous tissue in secondary lower extremity lymphedema. Ann Vasc Dis. 2013;6(2):180-8. doi: 10.3400/avd.oa.12.00102. Epub 2013 May 10.
- Background: PubMed 25010379Reed JL, Pipe AL. The talk test: a useful tool for prescribing and monitoring exercise intensity. Curr Opin Cardiol. 2014 Sep;29(5):475-80. doi: 10.1097/HCO.0000000000000097.
- Background: PubMed 30626269Mosti G, Cavezzi A. Compression therapy in lymphedema: Between past and recent scientific data. Phlebology. 2019 Sep;34(8):515-522. doi: 10.1177/0268355518824524. Epub 2019 Jan 9. No abstract available.
- Background: PubMed 21949976Lim CY, Seo HG, Kim K, Chung SG, Seo KS. Measurement of lymphedema using ultrasonography with the compression method. Lymphology. 2011 Jun;44(2):72-81.
- Background: PubMed 32268536Li CY, Kataru RP, Mehrara BJ. Histopathologic Features of Lymphedema: A Molecular Review. Int J Mol Sci. 2020 Apr 6;21(7):2546. doi: 10.3390/ijms21072546.
- Background: PubMed 35012367Lee DG, Lee S, Kim KT. Computed Tomography-Based Quantitative Analysis of Fibrotic Changes in Skin and Subcutaneous Tissue in Lower Extremity Lymphedema Following Gynecologic Cancer Surgery. Lymphat Res Biol. 2022 Oct;20(5):488-495. doi: 10.1089/lrb.2021.0069. Epub 2022 Jan 10.
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- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Compression bandage and Manual lymphatic drainage added to compression in people with Lower Extremity Lymphedema, run by Abant Izzet Baysal University at 1 site in Turkey (Türkiye).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Edema Assessment (time frame: Baseline, four week later). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06750679, which also lists 27 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2026.