Ultrasonographic Evaluation of Changes After Complex Decongestive Therapy

Lymphedema of Upper Arm Clinical Trial

Official title:

Evaluation of Tissue Changes Via Ultrasound After Complex Decongestive Therapy Phase I for Breast Cancer Related Lymphedema

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04139291
• Other study ID #: 09.2019.866
• Status: Not yet recruiting
• Phase: N/A
• Start date: October 20, 2019
• Est. completion date: March 30, 2020

Study information

• Verified date: October 2019
• Source: Marmara University
• Contact: Esra Giray, MD
• Phone: +902166570606162
• Email: girayesra[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to evaluate tissue changes via ultrasound after complex decongestive therapy.

Description:

Lymphedema can be defined as the abnormal accumulation of protein-rich interstitial fluid that occurs primarily as a consequence of malformation, dysplasia, or acquired disruption of lymphatic circulation. Lymph stasis, which results in peripheral lymphedema, is characterized by edema and adipose tissue proliferation. As a vicious cycle of lymphedema progression, lymph stasis stimulates chronic inflammation because of uncontrolled responses of macrophages and CD4+ (cluster of differentiation 4) cells; fat accumulation also causes chronic inflammation by infiltration and activation of macrophages that produce inflammatory cytokines, which further promote lymph stasis directly or indirectly by decreasing lymphatic pumping and increasing capillary filtration. Lymphedema secondary to breast cancer is caused by the disruption of the lymphatic system, which in the initial stages leads to the accumulation of fluid in the interstitial tissue space and eventually is clinically presented as swelling of the arm, shoulder, neck, or torso. Complex decongestive physical therapy is a widely used nonoperative treatment of breast cancer-related lymphedema. The extremity volume has been one of the major parameters representing the treatment results of complex decongestive physical therapy. However, the increase in extremity volume in lymphedema can be caused both by tissue fluid accumulation and by pathologic tissue proliferation, which cannot be assessed separately at present. Accordingly, the volume or circumference measurement alone may not clarify how these phenomena are modified by complex decongestive physical therapy. Suehiro et al. developed subcutaneous echogenicity grade (SEG) and subcutaneous echo-free space (SEFS) grade via B-mode ultrasonography, allowing semiquantitation of nonspecific subcutaneous tissue inflammation and fluid accumulation. Increase in SEG is attributed to increased cell density and increased collagen content in the tissue and it is considered to indicate the presence of ongoing or previous inflammation in the area. SEFS represents the fluid accumulated in the spaces between superficial fasciae, which is freely mobile in the spaces. Recently, Suehiro et al. have investigated the impact of aggressive decongestion in limbs with lymphedema without SEFS in subcutaneous tissue ultrasonography. According to their results, the impact of aggressive decongestion seemed limited in patients with lymphedema without SEFS. But it was a retrospective study which may be a limitation to draw a firm conclusion. Therefore, the aim of this study is to evaluate tissue changes via ultrasound after complex decongestive therapy.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: March 30, 2020
• Est. primary completion date: March 20, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

-Patients with unilateral postmastectomy lymphedema with a International Society of Lymphology-ISL) stage 2 and 3

Exclusion Criteria:

• Bilateral lymphedema

• The patients who had known systemic edematogenic conditions (e.g., cardiac/hepatic/renal failure, terminal cancer, on chemotherapy), and/or with cancer recurrence

• Patients with contraindications for application of complex decongestive therapy (active cutaneous infection, deep vein thrombosis, cardiac edema, and peripheral artery disease)

Related Conditions & MeSH terms

• Breast Cancer Lymphedema
• Lymphedema
• Lymphedema of Upper Arm

Intervention

Other:
• Complex decongestive therapy phase 1
Complex decongestive therapy-phase 1 program consist of meticulous skin and nail care, manuel lymphatic drainage, compression bandages, and remedial exercises. All patients will receive manual lymphatic drainage for three times a week (Monday-Wednesday-Friday) during 4 weeks, 50 minutes a day (a total of 12 sessions) by a trained lymphatic massage therapist.

Locations

Country	Name	City	State
Turkey	Esra Giray	Istanbul

Sponsors (1)

Lead Sponsor	Collaborator
Marmara University

Country where clinical trial is conducted

Turkey, 

References & Publications (5)

Giray E, Yagci I. Diagnostic accuracy of interlimb differences of ultrasonographic subcutaneous tissue thickness measurements in breast cancer-related arm lymphedema. Lymphology. 2019;52(1):1-10. — View Citation

Giray E, Yagci I. Interrater and Intrarater Reliability of Subcutaneous Echogenicity Grade and Subcutaneous Echo-Free Space Grade in Breast Cancer-Related Lymphedema. Lymphat Res Biol. 2019 Oct;17(5):518-524. doi: 10.1089/lrb.2018.0053. Epub 2018 Dec 20. — View Citation

Sezgin Ozcan D, Dalyan M, Unsal Delialioglu S, Duzlu U, Polat CS, Koseoglu BF. Complex Decongestive Therapy Enhances Upper Limb Functions in Patients with Breast Cancer-Related Lymphedema. Lymphat Res Biol. 2018 Oct;16(5):446-452. doi: 10.1089/lrb.2017.00 — View Citation

Suehiro K, Morikage N, Ueda K, Samura M, Takeuchi Y, Nagase T, Mizoguchi T, Hamano K. Aggressive Decongestion in Limbs with Lymphedema without Subcutaneous Echo-Free Space. Ann Vasc Surg. 2018 Nov;53:205-211. doi: 10.1016/j.avsg.2018.04.033. Epub 2018 Aug — View Citation

Suehiro K, Morikage N, Yamashita O, Harada T, Samura M, Takeuchi Y, Mizoguchi T, Nakamura K, Hamano K. Skin and Subcutaneous Tissue Ultrasonography Features in Breast Cancer-Related Lymphedema. Ann Vasc Dis. 2016;9(4):312-316. doi: 10.3400/avd.oa.16-00086 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Subcutaneous Echogenicity Grade (SEG) medial forearm (MFA)	Medial forearm (MFA): from the medial side of the forearm to the brachioradial muscle	before treatment (T0)
Primary	Subcutaneous Echo-Free Space Grade (SEFS) medial forearm (MFA)	Medial forearm (MFA): from the medial side of the forearm to the brachioradial muscle SEFS grade Grade 0: No SEFS. Grade 1: Horizontally oriented (<45 degrees to the skin) SEFS only. Grade 2: Presence of vertically oriented (‡45 degrees to the skin) SEFS bridging the horizontally oriented SEFS	before treatment (T0)
Primary	Subcutaneous tissue thickness measurement via ultrasound over medial forearm (MFA)	SEG grade of medial forearm (MFA): from the medial side of the forearm to the brachioradial muscle Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.	before treatment (T0)
Primary	Subcutaneous Echogenicity Grade (SEG) medial forearm (MFA)	SEG grade of medial forearm (MFA): from the medial side of the forearm to the brachioradial muscle Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Primary	Subcutaneous Echo-Free Space Grade (SEFS) medial forearm (MFA)	Medial forearm (MFA): from the medial side of the forearm to the brachioradial muscle SEFS grade Grade 0: No SEFS. Grade 1: Horizontally oriented (<45 degrees to the skin) SEFS only. Grade 2: Presence of vertically oriented (‡45 degrees to the skin) SEFS bridging the horizontally oriented SEFS	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Primary	Subcutaneous tissue thickness measurement via ultrasound over medial forearm (MFA)	Medial forearm (MFA): from the medial side of the forearm to the brachioradial muscle	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Secondary	Limb volume measurement	Limb volume will be calculated based on truncated cone method from circumference measurements	before treatment (T0)
Secondary	Limb volume measurement	Limb volume will be calculated based on truncated cone method from circumference measurements	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Secondary	Subcutaneous Echogenicity Grade (SEG) Medial upper arm (MUA)	SEG grade of medial upper arm (MUA): from the medial side of the upper arm to the biceps brachii muscle Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.	before treatment (T0)
Secondary	Subcutaneous Echo-Free Space Grade (SEFS) Medial upper arm (MUA)	Medial upper arm (MUA): from the medial side of the upper arm to the biceps brachii muscle SEFS grade Grade 0: No SEFS. Grade 1: Horizontally oriented (<45 degrees to the skin) SEFS only. Grade 2: Presence of vertically oriented (‡45 degrees to the skin) SEFS bridging the horizontally oriented SEFS	before treatment (T0)
Secondary	Subcutaneous tissue thickness measurement via ultrasound over medial upper arm (MUA)	SEG grade of medial upper arm (MUA): from the medial side of the upper arm to the biceps brachii muscle Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.	before treatment (T0)
Secondary	SEG grade of medial upper arm (MUA)	SEG grade of medial upper arm (MUA): from the medial side of the upper arm to the biceps brachii muscle Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Secondary	Subcutaneous Echo-Free Space Grade (SEFS) Medial upper arm (MUA)	Medial upper arm (MUA): from the medial side of the upper arm to the biceps brachii muscle SEFS grade Grade 0: No SEFS. Grade 1: Horizontally oriented (<45 degrees to the skin) SEFS only. Grade 2: Presence of vertically oriented (‡45 degrees to the skin) SEFS bridging the horizontally oriented SEFS	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Secondary	Subcutaneous tissue thickness measurement via ultrasound over medial upper arm (MUA)	Medial upper arm (MUA): from the medial side of the upper arm to the biceps brachii muscle	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Secondary	Subcutaneous Echogenicity Grade (SEG) Lateral upper arm (LUA)	SEG grade of lateral upper arm (LUA): from the lateral side of the upper arm to the biceps brachii muscle Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.	before treatment (T0)
Secondary	SEFS Lateral upper arm (LUA)	Lateral upper arm (LUA): from the lateral side of the upper arm to the biceps brachii muscle SEFS grade Grade 0: No SEFS. Grade 1: Horizontally oriented (<45 degrees to the skin) SEFS only. Grade 2: Presence of vertically oriented (‡45 degrees to the skin) SEFS bridging the horizontally oriented SEFS	before treatment (T0)
Secondary	Subcutaneous tissue thickness measurement via ultrasound over lateral upper arm (LUA)	SEG grade of lateral upper arm (LUA): from the lateral side of the upper arm to the biceps brachii muscle Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.	before treatment (T0)
Secondary	Subcutaneous Echogenicity Grade (SEG) Lateral upper arm (LUA)	SEG grade of lateral upper arm (LUA): from the lateral side of the upper arm to the biceps brachii muscle Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Secondary	SEFS Lateral upper arm (LUA)	Lateral upper arm (LUA): from the lateral side of the upper arm to the biceps brachii muscle SEFS grade Grade 0: No SEFS. Grade 1: Horizontally oriented (<45 degrees to the skin) SEFS only. Grade 2: Presence of vertically oriented (‡45 degrees to the skin) SEFS bridging the horizontally oriented SEFS	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Secondary	Subcutaneous tissue thickness measurement via ultrasound over lateral upper arm (LUA)	SEG grade of lateral upper arm (LUA): from the lateral side of the upper arm to the biceps brachii muscle Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Secondary	Subcutaneous Echogenicity Grade (SEG) Lateral forearm (LFA)	SEG grade of lateral forearm (LFA): from the lateral side of the forearm to the brachioradial muscle Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.	before treatment (T0)
Secondary	SEFS Lateral forearm (LFA)	Lateral forearm (LFA): from the lateral side of the forearm to the brachioradial muscle SEFS grade Grade 0: No SEFS. Grade 1: Horizontally oriented (<45 degrees to the skin) SEFS only. Grade 2: Presence of vertically oriented (‡45 degrees to the skin) SEFS bridging the horizontally oriented SEFS	before treatment (T0)
Secondary	Subcutaneous tissue thickness measurement via ultrasound over lateral forearm (LFA)	SEG grade of lateral forearm (LFA): from the lateral side of the forearm to the brachioradial muscle Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.	before treatment (T0)
Secondary	SEG grade of lateral forearm (LFA)	SEG grade of lateral forearm (LFA): from the lateral side of the forearm to the brachioradial muscle Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Secondary	SEFS Lateral forearm (LFA)	Lateral forearm (LFA): from the lateral side of the forearm to the brachioradial muscle SEFS grade Grade 0: No SEFS. Grade 1: Horizontally oriented (<45 degrees to the skin) SEFS only. Grade 2: Presence of vertically oriented (‡45 degrees to the skin) SEFS bridging the horizontally oriented SEFS	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Secondary	Subcutaneous tissue thickness measurement via ultrasound over lateral forearm (LFA)	Lateral forearm (LFA): from the lateral side of the forearm to the brachioradial muscle	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Secondary	Subcutaneous Echogenicity Grade (SEG) Dorsum of the hand (DH)	SEG grade of Dorsum of the hand (DH): on the first dorsal interosseous muscle of the hand.; Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.	before treatment (T0)
Secondary	SEFS Dorsum of the hand (DH)	Dorsum of the hand (DH): on the first dorsal interosseous muscle of the hand. SEFS grade Grade 0: No SEFS. Grade 1: Horizontally oriented (<45 degrees to the skin) SEFS only. Grade 2: Presence of vertically oriented (‡45 degrees to the skin) SEFS bridging the horizontally oriented SEFS	before treatment (T0)
Secondary	Subcutaneous tissue thickness measurement via ultrasound over dorsum of the hand (DH)	SEG grade of Dorsum of the hand (DH): on the first dorsal interosseous muscle of the hand.; Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.	before treatment (T0)
Secondary	SEG dorsum of the hand (DH)	SEG grade of Dorsum of the hand (DH): on the first dorsal interosseous muscle of the hand.; Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Secondary	SEFS Dorsum of the hand (DH)	Dorsum of the hand (DH): on the first dorsal interosseous muscle of the hand. SEFS grade Grade 0: No SEFS. Grade 1: Horizontally oriented (<45 degrees to the skin) SEFS only. Grade 2: Presence of vertically oriented (‡45 degrees to the skin) SEFS bridging the horizontally oriented SEFS	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Secondary	SEG grade of Dorsum of the hand (DH)	Dorsum of the hand (DH): on the first dorsal interosseous muscle of the hand. SEG grade of Dorsum of the hand (DH): on the first dorsal interosseous muscle of the hand.; Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Secondary	Subcutaneous Echogenicity Grade (SEG) wrist	SEG grade over wrist Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.	before treatment (T0)
Secondary	SEFS wrist	SEFS grade over wrist SEFS grade Grade 0: No SEFS. Grade 1: Horizontally oriented (<45 degrees to the skin) SEFS only. Grade 2: Presence of vertically oriented (‡45 degrees to the skin) SEFS bridging the horizontally oriented SEFS	before treatment (T0)
Secondary	Subcutaneous tissue thickness measurement via ultrasound over wrist	Subcutaneous tissue thickness measurement via ultrasound over wrist	before treatment (T0)
Secondary	Subcutaneous Echogenicity Grade (SEG) wrist	SEG grade over wrist Grade 0: No or little increase in echogenicity in the subcutaneous layer. Horizontal or obliquely oriented echogenic lines caused by connective tissue bundles are clearly observed. Grade 1: Diffused and monotonous increases in echogenicity in the subcutaneous layer. Echogenic lines are unclear but identifiable. Grade 2: Diffused increases in echogenicity. Echogenic lines are not identifiable.	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Secondary	SEFS wrist	SEFS grade over wrist SEFS grade Grade 0: No SEFS. Grade 1: Horizontally oriented (<45 degrees to the skin) SEFS only. Grade 2: Presence of vertically oriented (‡45 degrees to the skin) SEFS bridging the horizontally oriented SEFS	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)
Secondary	Subcutaneous tissue thickness measurement via ultrasound over wrist	Subcutaneous tissue thickness measurement via ultrasound over wrist	after treatment (T1) (through completion of four weeks of complex decongestive therapy phase 1)