Edema, Lymphedema
Conditions
Keywords
lymphedema, edema
Brief summary
To investigate whether addition of the Biobridge scaffold to the standard surgery for vascularized lymph node transfer will improve the outcome of surgical treatment in lymphedema of the upper arm.
Detailed description
The investigators will perform lymph scans (lymphoscintigrams) before surgery and one year following surgery to determine the success of the surgery. In addition, the volume of the operated arm will be monitored by repeated measurement with a tape measure. The investigators will also track bioimpedance, a painless technique to detect fluid in the tissues. The investigators will obtain small skin biopsies and blood samples to detect the biological changes that may occur as a result of successful surgery.
Interventions
DEVICEBiobridge and lymph node transfer
Biobridge is surgically implanted with conventional vascularized lymph node transfer surgery
Sponsors
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
The subject must be a breast cancer survivor, at least three years beyond completion of cancer therapy, free of clinical disease, and eligible for surgical intervention. * Ages 18 to 75 years (inclusive). * Swelling of 1 limb that is not completely reversed by elevation or compression * Stage II or greater lymphedema at screening, based on the International Society of Lymphology (ISL) staging system * Completion of a full course of complete decongestive therapy (CDT), according to ISL guidelines at least 8 weeks prior to screening, including use of compression garments for at least 8 weeks without change in regimen * Willingness to maintain a stable regimen of self-care, with consistent use of compression garments from screening through the entire study duration (through the safety follow-up visit). Self-bandaging, use of nighttime compression garments, and intermittent pneumatic compression devices are allowed, but the procedures and regimens must remain consistent from screening though the entire study duration. * Two consecutive measurements of limb volume (LV) in the affected limb taken at least 1 day apart during the screening period must be within 10% of each other. A maximum of 3 measurements can be taken. Affected limb volume ratio \>20% (affected limb compared to unaffected limb); volume measurements will be performed and volume ratio will be calculated at S1 and S2 visit. * Evidence of abnormal bioimpedance ratio, if feasible based upon unilateral disease: L-Dex \>10 units; bioimpedance performed at S1 and S1 * Willingness and ability to understand and the willingness to sign a written informed consent form document * Willingness and ability to comply with all study procedures, including measurement of skin thickness using skin calipers. * Participants must have NED, completed breast cancer therapy 3 years prior to enrollment. * ECOG 0- 2
Exclusion criteria
* Edema arising from increased capillary filtration will be excluded. * Inability to safely undergo general anesthesia and/or perioperative care related to vascularized lymph node transfer * Concurrent participation in a clinical trial of any other investigational drug or therapy, regardless of indication, within 1 month before screening or 5 times the drug's half-life, whichever is longer * Recent initiation of (≤8 weeks), or intention to initiate, CDPT or maintenance physiotherapy for lymphedema at any time during the duration of the study * Other medical condition that could lead to acute limb edema, such as (but not limited to) acute venous thrombosis * Other medical condition that could result in symptoms overlapping those of lymphedema in the affected limb (e.g., pain, swelling, decreased range of motion) * History of clotting disorder (hypercoagulable state) * Chronic (persistent) infection in the affected limb * Any other infection (unrelated to lymphedema) within 1 month prior to screening * Current evidence of malignancy or any high risk for breast cancer recurrence (Stage III or IV, ER/PR/HER-2 negative (triple negative) cancer , locally advanced disease, inflammatory breast cancer, \> 3 positive axillary lymph nodes, extracapsular nodal extension, invasive micropapillary breast carcinoma, or if performed, patients with a high risk of recurrence based on multi-gene signatures, e.g. BRCA1, BRCA 2, Oncotype DX (high risk recurrence score) or Mammaprint (poor risk signature) * Currently receiving chemotherapy or radiation therapy * Life expectancy \< 2 years for any reason * Pregnancy or nursing * Substance abuse (such as alcohol or drug abuse) within 6 months prior to screening * Significant or chronic renal insufficiency (defined as serum creatinine \> 2.5 mg/dL or an estimated glomerular filtration rate \[eGFR\] \< 30 mL/min at screening) or requires dialytic support * Hepatic dysfunction, defined as alanine transaminase (ALT) or aspartate transaminase (AST) levels \> 3 × upper limit of the normal range (ULN) and/or bilirubin level \> 2 × ULN at screening * Absolute neutrophil count \< 1500 mm3 at screening * Hemoglobin concentration \< 9 g/dL at screening * Known sensitivity to porcine products * Any reason (in addition to those listed above) that, in the opinion of the investigator, precludes full participation in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Limb Volume | 1 year | Lymphoscintigraphy, a measure of limb volume indicative of adequate limb drainage, was conducted on the arm receiving BioBridge implantation (affected arm) and the contralateral (unaffected) arm, before surgery (baseline) and 1 year following surgical implantation of the Biobridge device. The outcome is reported as the median difference in the pre-implantation baseline value and the value 1 year after surgery for each arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serial Lymphoscintigraphy (LSG) | 1 year | Lymphoscintigraphy, a measure of limb volume for which changes are indicative of adequate limb drainage, was conducted on the arm receiving the BioBridge implantation (baseline) and 1 year following the Biobridge implantation. The outcome is reported as the median difference in measured volume for affected arm from baseline to 1 year. |
| Bioimpedance Spectroscopy | 1 year | Bioimpedance spectroscopy (BIS) is a non-invasive technique to measure the volume of fluid in various parts of the body, and can be used to assess the extent of lymphedema. BIS involves passing an extremely low-strength electrical current through the area and measuring how the flow of the current is slowed by the fluid in the body, and is reported as Ri in ohms, meaning the resistance of the intracellular fluid. BIS was conducted on the arm with the BioBridge implant, at baseline and 1 year after surgery. The outcome is reported as the median difference between baseline and 1 year after surgery in the arm receiving the BioBridge implant. |
| Caliper Skin-fold Thickness | 1 year | Skin fold thickness as measured by calipers was used as a measure of fluid retention. Skin fold thickness was measured at the upper arm, forearm, and back of the hand, at baseline and at 1 year following surgical implantation of the Biobridge device. An increase in skin thickness means increased fluid retention. The outcome is reported as the median difference of skin fold thickness in millimeters (mm) for each location on the arm receiving the BioBridge implant, from baseline to 1 year. |
| Cutaneous Punch Biopsy of Skin | 1 year | Serial changes in histopathology will be determined via a blinded assessment of serial cutaneous punch biopsies specimens. |
| Quality of Life for Limb Lymphoedema (LYMQOL) | 1 year | Quality-of-life was assessed using the LYMQOL survey, a 5-question survey for improved function, appearance, symptoms, mood, and overall QOL. Overall QoL was reported on a 10-point scale with 10 being best, and the other assessments were for disease impact on a 4-point response scale consisting of 1 (none), 2 (a little), 3 (quite a bit), 4 (a lot), with lower values representing minimal disease (lymphedema) impact on the parameter and higher values representing a greater negative effect on the parameter. The outcome is reported as the median. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Biobridge and Lymph Node Transfer The investigators will investigate whether addition of the Biobridge scaffold to the standard surgery for vascularized lymph node transfer will improve the outcome of surgical treatment in lymphedema of the upper arm. The investigators will perform lymph scans (lymphoscintigrams) before surgery and one year following surgery to determine the success of the surgery. In addition, the volume of the operated arm will be monitored by repeated measurement with a tape measure. The investigators will also track bioimpedance, a painless technique to detect fluid in the tissues. The investigators will obtain small skin biopsies and blood samples to detect the biological changes that may occur as a result of successful surgery.
Biobridge and lymph node transfer: Biobridge is surgically implanted with conventional vascularized lymph node transfer surgery | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Biobridge and Lymph Node Transfer |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
Change in Limb Volume
Lymphoscintigraphy, a measure of limb volume indicative of adequate limb drainage, was conducted on the arm receiving BioBridge implantation (affected arm) and the contralateral (unaffected) arm, before surgery (baseline) and 1 year following surgical implantation of the Biobridge device. The outcome is reported as the median difference in the pre-implantation baseline value and the value 1 year after surgery for each arm.
Time frame: 1 year
Population: The units analyses are the affected arm (received BioBridge implant) and the unaffected contralateral arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Biobridge and Lymph Node Transfer | Change in Limb Volume | BioBridge implant arm | -15 mL |
| Biobridge and Lymph Node Transfer | Change in Limb Volume | Unaffected contralateral arm | -202 mL |
Secondary
Bioimpedance Spectroscopy
Bioimpedance spectroscopy (BIS) is a non-invasive technique to measure the volume of fluid in various parts of the body, and can be used to assess the extent of lymphedema. BIS involves passing an extremely low-strength electrical current through the area and measuring how the flow of the current is slowed by the fluid in the body, and is reported as Ri in ohms, meaning the resistance of the intracellular fluid. BIS was conducted on the arm with the BioBridge implant, at baseline and 1 year after surgery. The outcome is reported as the median difference between baseline and 1 year after surgery in the arm receiving the BioBridge implant.
Time frame: 1 year
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Biobridge and Lymph Node Transfer | Bioimpedance Spectroscopy | Baseline | 951.8 ohms |
| Biobridge and Lymph Node Transfer | Bioimpedance Spectroscopy | 1 year | 977.3 ohms |
Secondary
Caliper Skin-fold Thickness
Skin fold thickness as measured by calipers was used as a measure of fluid retention. Skin fold thickness was measured at the upper arm, forearm, and back of the hand, at baseline and at 1 year following surgical implantation of the Biobridge device. An increase in skin thickness means increased fluid retention. The outcome is reported as the median difference of skin fold thickness in millimeters (mm) for each location on the arm receiving the BioBridge implant, from baseline to 1 year.
Time frame: 1 year
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Biobridge and Lymph Node Transfer | Caliper Skin-fold Thickness | Baseline | 2.5 millimeters (mm) |
| Biobridge and Lymph Node Transfer | Caliper Skin-fold Thickness | 1 Year | 3.25 millimeters (mm) |
| Caliper Skin-fold Thickness - Forearm | Caliper Skin-fold Thickness | Baseline | 3.5 millimeters (mm) |
| Caliper Skin-fold Thickness - Forearm | Caliper Skin-fold Thickness | 1 Year | 3.25 millimeters (mm) |
| Caliper Skin-fold Thickness - Hand | Caliper Skin-fold Thickness | Baseline | 2.5 millimeters (mm) |
| Caliper Skin-fold Thickness - Hand | Caliper Skin-fold Thickness | 1 Year | 2.25 millimeters (mm) |
Secondary
Cutaneous Punch Biopsy of Skin
Serial changes in histopathology will be determined via a blinded assessment of serial cutaneous punch biopsies specimens.
Time frame: 1 year
Population: The per-protocol analysis was specified to be a blinded analysis, but with only a single set of specimens the analysis could not be conducted as defined.
Secondary
Quality of Life for Limb Lymphoedema (LYMQOL)
Quality-of-life was assessed using the LYMQOL survey, a 5-question survey for improved function, appearance, symptoms, mood, and overall QOL. Overall QoL was reported on a 10-point scale with 10 being best, and the other assessments were for disease impact on a 4-point response scale consisting of 1 (none), 2 (a little), 3 (quite a bit), 4 (a lot), with lower values representing minimal disease (lymphedema) impact on the parameter and higher values representing a greater negative effect on the parameter. The outcome is reported as the median.
Time frame: 1 year
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Biobridge and Lymph Node Transfer | Quality of Life for Limb Lymphoedema (LYMQOL) | 1 year | 9 units on a scale |
| Biobridge and Lymph Node Transfer | Quality of Life for Limb Lymphoedema (LYMQOL) | Baseline | 7 units on a scale |
| Caliper Skin-fold Thickness - Forearm | Quality of Life for Limb Lymphoedema (LYMQOL) | Baseline | 2.2 units on a scale |
| Caliper Skin-fold Thickness - Forearm | Quality of Life for Limb Lymphoedema (LYMQOL) | 1 year | 1.2 units on a scale |
| Caliper Skin-fold Thickness - Hand | Quality of Life for Limb Lymphoedema (LYMQOL) | 1 year | 1.6 units on a scale |
| Caliper Skin-fold Thickness - Hand | Quality of Life for Limb Lymphoedema (LYMQOL) | Baseline | 3.4 units on a scale |
| LYMQOL Survey - Symptoms | Quality of Life for Limb Lymphoedema (LYMQOL) | Baseline | 2.6 units on a scale |
| LYMQOL Survey - Symptoms | Quality of Life for Limb Lymphoedema (LYMQOL) | 1 year | 1.5 units on a scale |
| LYMQOL Survey - Mood | Quality of Life for Limb Lymphoedema (LYMQOL) | 1 year | 1.3 units on a scale |
| LYMQOL Survey - Mood | Quality of Life for Limb Lymphoedema (LYMQOL) | Baseline | 1.4 units on a scale |
Secondary
Serial Lymphoscintigraphy (LSG)
Lymphoscintigraphy, a measure of limb volume for which changes are indicative of adequate limb drainage, was conducted on the arm receiving the BioBridge implantation (baseline) and 1 year following the Biobridge implantation. The outcome is reported as the median difference in measured volume for affected arm from baseline to 1 year.
Time frame: 1 year
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Biobridge and Lymph Node Transfer | Serial Lymphoscintigraphy (LSG) | Baseline | 2295 mL |
| Biobridge and Lymph Node Transfer | Serial Lymphoscintigraphy (LSG) | 1 year | 2280 mL |