Treatment of Breast Cancer-related Lymphedema With Stem Cells and Fat Grafting

Study Overview
=================
Brief Summary
-----------------
Breast cancer-related lymphedema is one of the most common and feared consequences of breast cancer treatment. Currently, lymphedema is primarily addressed conservatively with compression garments. Regenerative medicine may provide a new treatment option for lymphedema. This Phase 3 trial will examine the efficacy, effectiveness and safety of freshly isolated adipose-derived stromal cells administered in conjunction with a fat grafting procedure to the affected axillary region.

Official Title
-----------------
Treatment of Breast Cancer-related Lymphedema With Stem Cells and Fat Grafting

Conditions
-----------------
Lymphedema

Intervention / Treatment
-----------------
* Procedure: Liposuction
* Procedure: Fat graft
* Procedure: Sham graf (Saline injection)
* Biological: Stem cell injection
* Procedure: Saline injection


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Unilateral arm lymphedema secondary to breast cancer treatment including lymph node dissection. Cancer free for at least 1 year The patient understands the nature and purpose of this study and the study procedures and has signed informed consent. The opposite upper extremity is healthy (no lymphedema). ASA score of 1 or 2. The patient is able to read, understand, and complete Danish questionnaires. Pitting lymphedema ISL grade 1 or 2. A minimum circumference difference of 2cm or a minimum volume difference of 200mL. Exclusion Criteria: Pregnant or lactating. Bilateral lymphedema Current or previous malignancies other than breast cancer. Insulin-dependent diabetes. Diagnosed with any form of psychotic disorder, which may impact study participation. Not ceased smoking during treatment. Active implantables (e.g. pacemaker or neurostimulator) Unrealistic treatment expectations. Known hepatitis, HIV or syphilis infection.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active treatment<br> | Procedure: Liposuction<br>* Liposuction is performed on the abdomen or thighs.<br>Procedure: Fat graft<br>* 30mL harvested lipoaspirate is injected at the affected axillary site.<br>* Other names: lipotransfer;Biological: Stem cell injection<br>* 4mL stem cell suspension injected at the affected axillary site.<br>|
| Placebo Comparator: Placebo treatment<br> | Procedure: Liposuction<br>* Liposuction is performed on the abdomen or thighs.<br>Procedure: Sham graf (Saline injection)<br>* 30mL saline is injected at the affected axillary site.<br>Procedure: Saline injection<br>* 4mL saline injected at the affected axillary site.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in arm volume | Assessed using clinical circumference measurement | Baseline, 3, 6, 9 and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of treatments: Assessed by asking the patient at each visit | Any side effects to treatments. Assessed by asking the patient at each visit. | Baseline, 3, 6, 9 and 12 months | 
| Subjective changes assessed using the LYMPH-ICF (Lymphoedema Functioning, Disability and Health) questionaire | Subjective change of lymphedema assessed by questionnaire. Range: 0-100. 100 being the most bothered. | Baseline, 3, 6, 9 and 12 months | 
| Subjective changes assessed using DASH (DISABILITIES OF THE ARM, SHOULDER AND HAND) questionaire | Subjective change of lymphedema assessed by questionnaire. Range: 1-5. 5 being the most bothered | Baseline, 3, 6, 9 and 12 months | 
| Subjective changes assessed using SF-36 questionnaire | Subjective change of quality of life assessed by questionnaire. Range: 0-100. 0 being the most bothered. | Baseline, 3, 6, 9 and 12 months | 
| Change in lymph drainage | Change in lymph drainage assessed by indocyanine-green lymphangiography | Baseline and 12 months | 
| Change in conservative lymphedema treatment | Change in use or type of conservative lymphedema treatments | Baseline, 3, 6, 9 and 12 months | 
| Change in adverse lymphedema-related events | Change in infection rates and sick-days due to lymphedema. | Baseline, 3, 6, 9 and 12 months | 
| Change in L-DEX score (bioimpedance) | Change in L-DEX score of lymphedema arm derived from bioimpedance. Higher values mean more fluid in the lymphedema arm compared to the healthy arm. | Baseline, 3, 6, 9 and 12 months | 
| Change in weight and arm tissue composition | Assessed using dual energy x-ray absorptiometry (DXA) scan. Change in values from baseline. | Baseline, 3, 6, 9 and 12 months |