Secondary Lymphedema
Conditions
Keywords
lymphedema, therapy, swelling, graded negative pressure, complete decongestive therapy
Brief summary
Persons with secondary arm and/or upper quadrant lymphedema following cancer therapies commonly are prescribed complete decongestive therapy as a course of management of their lymphedema. The investigators will perform a repeated-measures cross-over trial to test the hypothesis that mobilization of protein enriched hardened tissue using graded negative pressure therapy in conjunction with complete decongestive therapy (CDT) is more effective to standard CDT alone for secondary lymphedema management.
Detailed description
The goal of this work is to apply novel, noninvasive magnetic resonance imaging (MRI) methods for visualizing lymphatic circulation dysfunction to test a fundamental hypothesis about secondary lymphedema conservative decongestive therapy. Breast cancer treatment-related lymphedema (BCRL) arises secondary to surgical axillary lymph node (LN) dissection and irritation, and is a chronic and lifelong condition affecting a high 21.4% of patients receiving common breast cancer therapies. Persons with secondary lymphedema following axillary lymph node removal also include undergoing treatment for other cancers, such as melanoma involving the upper body, necessitating the need for axially lymph node removal. Improving lymphedema management represents a major clinical need, and emerging efforts focus on improving quality of life through optimizing post-surgical complex decongestive therapy (CDT), and exploring novel pharmacological and surgical procedures. Here, the investigators will perform a repeated-measures cross-over trial to test the hypothesis that mobilization of protein enriched hardened tissue using graded negative pressure therapy in conjunction with complete decongestive therapy (CDT) is more effective to standard CDT alone for secondary lymphedema management. Both of these conservative physical therapy treatments are commonly employed for treatment of secondary lymphedema.
Interventions
PROCEDURECDT with Negative Pressure
Complete decongestive therapy (physical therapy conservative intervention of compression, manual lymphatic drainage, skin care and exercises) in conjunction with manual intervention of graded negative pressure application for lymphatic stimulation/ tissue clearance
PROCEDURECDT alone
Complete decongestive therapy (physical therapy conservative intervention of compression, manual lymphatic drainage, skin care and exercises) for lymphatic stimulation/ tissue clearance
Sponsors
National Institutes of Health (NIH)
National Institute of Nursing Research (NINR)
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
30 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Females with a diagnosis of secondary arm and/or upper quadrant lymphedema following cancer treatments
Exclusion criteria
* Subjects who have any type of non-MRI compatible bioimplant activated by mechanical, electronic, or magnetic means (e.g., cochlear implants, pacemakers, neurostimulators, biostimulators, electronic infusion pumps, etc.) or are not able to comfortably be able to tolerate the limited fit of the MRI * Subjects who have any type of ferromagnetic bioimplant that could potentially be displaced. * Subjects who may have shrapnel embedded in their bodies (such as from war wounds), metal workers and machinists (potential for metallic fragments in or near the eyes). * Pregnant women will be excluded from the MRI portion of the study only * Subjects who have open wounds on either ankle or top of foot because of contraindications with placement of electrodes to obtain the L-DEX U400 readings. * Persons with heart pacemakers. * Persons with bilateral arm lymphedema (or bilateral risk) or pre-existing lymphedema/edema in the upper body prior to cancer treatments.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessing a Change in Bioimpedance Spectroscopy (BIS) | At baseline and at 6-8 weeks following the completion of therapy | BIS is a noninvasive technology measuring the resistance and reactance of tissue across multiple electrical frequencies using the Impedimed U400 device. By distinguishing ICF from ECF, BIS allows sensitive detection of ECF accumulation, a hallmark of lymphedema. Impedimed's proprietary calculations convert impedance ratios of limbs (involved vs unaffected) into a single output known as LDEX (lymphedema index) with an output normal range of -10 to +10. In situations of overt signs of lymphedema, the LDEX value could be up to 120. This single output value (LDEX) is used in lymphedema research and clinical care to monitor lymphedema progress and response to lymphedema therapy. The LDEX outcome in this study represents the change in LDEX value of the arms from study baseline and at 6-8 weeks following the completion of therapy where a negative value shows a positive response from the therapy intervention by indicating a reduction in the LDEX value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessing a Change in Quality of Life Via Patient Specific Functional Scale (PSFS) | At baseline (pre-intervention) and at 6-8 weeks following the completion of each therapy (post-intervention) | The Patient Specific Functional Scale (PSFS) was developed as a self-report outcome measure of function that could be used in participants with varying levels of independence. Each participant chose a set of three daily activities and rated the level of ease and comfort with which they could complete them pre and post each intervention. Rating scale starts at 0 (unable to perform activity) and goes to goes up to 10 (able to perform activity at the same level as before injury or problem). The closer to 10, the more favorable the number is. |
| Tissue Dielectric Constant (TDC) Measurement Difference Above the Elbow | At baseline (pre-intervention) and at 6-8 weeks following the completion of each therapy ([post intervention ) | TDC measures the skin-to-fat water content in tissues. The location was chosen given the propensity of swelling and discomfort in the area for participant population. This measurement compares the TDC value in the affected limb versus the unaffected limb, therefore the closer the TDC measurement difference is to zero, the more favorable the value is. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CDT Alone First, Then CDT With Negative Pressure A total of 9 therapy visits (75minutes duration) of CDT alone without LymphaTouch was administered for 6 weeks. After a six month washout period, participants were brought back in for another 9 therapy visits (75minutes duration) administered over 6 weeks of CDT with Negative Pressure.
CDT alone: Complete decongestive therapy (physical therapy conservative intervention of compression, manual lymphatic drainage, skin care and exercises) for lymphatic stimulation/ tissue clearance.
CDT with Negative Pressure: Complete decongestive therapy (physical therapy conservative intervention of compression, manual lymphatic drainage, skin care and exercises) in conjunction with manual intervention of graded negative pressure application for lymphatic stimulation/ tissue clearance. | 6 |
| CDT With Negative Pressure First, Then CDT Alone A total of 9 therapy visits (75minutes duration) of CDT with LymphaTouch Negative Pressure was administered for 6 weeks. After a six month washout period, participants were brought back in for another 9 therapy visits (75minutes duration) administered over 6 weeks of CDT Alone, without Negative Pressure.
CDT Alone: Complete decongestive therapy (physical therapy conservative intervention of compression, manual lymphatic drainage, skin care and exercises) for lymphatic stimulation/ tissue clearance.
CDT with Negative Pressure: Complete decongestive therapy (physical therapy conservative intervention of compression, manual lymphatic drainage, skin care and exercises) in conjunction with manual intervention of graded negative pressure application for lymphatic stimulation/ tissue clearance. | 9 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 0 |
Baseline characteristics
| Characteristic | CDT Alone First, Then CDT With Negative Pressure | CDT With Negative Pressure First, Then CDT Alone | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 8 Participants | 14 Participants |
| Age, Continuous | 49.5 years | 51.5 years | 50.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 9 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 6 participants | 9 participants | 15 participants |
| Sex: Female, Male Female | 6 Participants | 9 Participants | 15 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 0 / 15 | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
Assessing a Change in Bioimpedance Spectroscopy (BIS)
BIS is a noninvasive technology measuring the resistance and reactance of tissue across multiple electrical frequencies using the Impedimed U400 device. By distinguishing ICF from ECF, BIS allows sensitive detection of ECF accumulation, a hallmark of lymphedema. Impedimed's proprietary calculations convert impedance ratios of limbs (involved vs unaffected) into a single output known as LDEX (lymphedema index) with an output normal range of -10 to +10. In situations of overt signs of lymphedema, the LDEX value could be up to 120. This single output value (LDEX) is used in lymphedema research and clinical care to monitor lymphedema progress and response to lymphedema therapy. The LDEX outcome in this study represents the change in LDEX value of the arms from study baseline and at 6-8 weeks following the completion of therapy where a negative value shows a positive response from the therapy intervention by indicating a reduction in the LDEX value.
Time frame: At baseline and at 6-8 weeks following the completion of therapy
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CDT Alone | Assessing a Change in Bioimpedance Spectroscopy (BIS) | 1.3 Change of score on a scale | Standard Deviation 8 |
| CDT With Negative Pressure | Assessing a Change in Bioimpedance Spectroscopy (BIS) | 1.8 Change of score on a scale | Standard Deviation 5.1 |
Secondary
Assessing a Change in Quality of Life Via Patient Specific Functional Scale (PSFS)
The Patient Specific Functional Scale (PSFS) was developed as a self-report outcome measure of function that could be used in participants with varying levels of independence. Each participant chose a set of three daily activities and rated the level of ease and comfort with which they could complete them pre and post each intervention. Rating scale starts at 0 (unable to perform activity) and goes to goes up to 10 (able to perform activity at the same level as before injury or problem). The closer to 10, the more favorable the number is.
Time frame: At baseline (pre-intervention) and at 6-8 weeks following the completion of each therapy (post-intervention)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CDT Alone | Assessing a Change in Quality of Life Via Patient Specific Functional Scale (PSFS) | At baseline (Pre-Intervention) | 5.1 PSFS score | Standard Deviation 2 |
| CDT Alone | Assessing a Change in Quality of Life Via Patient Specific Functional Scale (PSFS) | at 6-8 weeks following the completion of each therapy (Post-Intervention) | 6.6 PSFS score | Standard Deviation 2.5 |
| CDT With Negative Pressure | Assessing a Change in Quality of Life Via Patient Specific Functional Scale (PSFS) | At baseline (Pre-Intervention) | 5.0 PSFS score | Standard Deviation 1.8 |
| CDT With Negative Pressure | Assessing a Change in Quality of Life Via Patient Specific Functional Scale (PSFS) | at 6-8 weeks following the completion of each therapy (Post-Intervention) | 7.0 PSFS score | Standard Deviation 1.8 |
Secondary
Tissue Dielectric Constant (TDC) Measurement Difference Above the Elbow
TDC measures the skin-to-fat water content in tissues. The location was chosen given the propensity of swelling and discomfort in the area for participant population. This measurement compares the TDC value in the affected limb versus the unaffected limb, therefore the closer the TDC measurement difference is to zero, the more favorable the value is.
Time frame: At baseline (pre-intervention) and at 6-8 weeks following the completion of each therapy ([post intervention )
Population: While participants started in different groups, all 15 analyzed participants went through both arms of the study after a washout period. This number represents all participants who completed both arms of the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CDT Alone | Tissue Dielectric Constant (TDC) Measurement Difference Above the Elbow | At Baseline (Pre-Intervention) | 9.8 TDC % change | Standard Deviation 10.8 |
| CDT Alone | Tissue Dielectric Constant (TDC) Measurement Difference Above the Elbow | 6-8 weeks following the completion of each therapy (Post-Intervention) | 8.9 TDC % change | Standard Deviation 9.5 |
| CDT With Negative Pressure | Tissue Dielectric Constant (TDC) Measurement Difference Above the Elbow | At Baseline (Pre-Intervention) | 9.4 TDC % change | Standard Deviation 9.7 |
| CDT With Negative Pressure | Tissue Dielectric Constant (TDC) Measurement Difference Above the Elbow | 6-8 weeks following the completion of each therapy (Post-Intervention) | 4.8 TDC % change | Standard Deviation 5.8 |