<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03776721</url>
  </required_header>
  <id_info>
    <org_study_id>S-20180117</org_study_id>
    <nct_id>NCT03776721</nct_id>
  </id_info>
  <brief_title>Treatment of Breast Cancer-related Lymphedema With Stem Cells and Fat Grafting</brief_title>
  <official_title>Treatment of Breast Cancer-related Lymphedema With Stem Cells and Fat Grafting</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Odense University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Odense University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Breast cancer-related lymphedema is one of the most common and feared consequences of breast&#xD;
      cancer treatment. Currently, lymphedema is primarily addressed conservatively with&#xD;
      compression garments. Regenerative medicine may provide a new treatment option for&#xD;
      lymphedema. This Phase 3 trial will examine the efficacy, effectiveness and safety of freshly&#xD;
      isolated adipose-derived stromal cells administered in conjunction with a fat grafting&#xD;
      procedure to the affected axillary region.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 18, 2018</start_date>
  <completion_date type="Actual">June 1, 2021</completion_date>
  <primary_completion_date type="Actual">June 1, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>All patients undergo the same liposuction procedure. During general anesthesia, patients are randomized to either fat grafting or sham grafting with saline injection to the axilla. After stem cell suspension, patients receive either stem cell or saline injection depending on randomization using masked syringes.&#xD;
Participants are blinded, care providers postoperatively are blinded, primary investigator is blinded and all outcome assessors are blinded. The surgeon performing the liposuction and the stem-cell staff are unblinded.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in arm volume</measure>
    <time_frame>Baseline, 3, 6, 9 and 12 months</time_frame>
    <description>Assessed using clinical circumference measurement</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety of treatments: Assessed by asking the patient at each visit</measure>
    <time_frame>Baseline, 3, 6, 9 and 12 months</time_frame>
    <description>Any side effects to treatments. Assessed by asking the patient at each visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subjective changes assessed using the LYMPH-ICF (Lymphoedema Functioning, Disability and Health) questionaire</measure>
    <time_frame>Baseline, 3, 6, 9 and 12 months</time_frame>
    <description>Subjective change of lymphedema assessed by questionnaire. Range: 0-100. 100 being the most bothered.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subjective changes assessed using DASH (DISABILITIES OF THE ARM, SHOULDER AND HAND) questionaire</measure>
    <time_frame>Baseline, 3, 6, 9 and 12 months</time_frame>
    <description>Subjective change of lymphedema assessed by questionnaire. Range: 1-5. 5 being the most bothered</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subjective changes assessed using SF-36 questionnaire</measure>
    <time_frame>Baseline, 3, 6, 9 and 12 months</time_frame>
    <description>Subjective change of quality of life assessed by questionnaire. Range: 0-100. 0 being the most bothered.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in lymph drainage</measure>
    <time_frame>Baseline and 12 months</time_frame>
    <description>Change in lymph drainage assessed by indocyanine-green lymphangiography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in conservative lymphedema treatment</measure>
    <time_frame>Baseline, 3, 6, 9 and 12 months</time_frame>
    <description>Change in use or type of conservative lymphedema treatments</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in adverse lymphedema-related events</measure>
    <time_frame>Baseline, 3, 6, 9 and 12 months</time_frame>
    <description>Change in infection rates and sick-days due to lymphedema.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in L-DEX score (bioimpedance)</measure>
    <time_frame>Baseline, 3, 6, 9 and 12 months</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in weight and arm tissue composition</measure>
    <time_frame>Baseline, 3, 6, 9 and 12 months</time_frame>
    <description>Assessed using dual energy x-ray absorptiometry (DXA) scan. Change in values from baseline.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">80</enrollment>
  <condition>Lymphedema</condition>
  <arm_group>
    <arm_group_label>Active treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo treatment</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Liposuction</intervention_name>
    <description>Liposuction is performed on the abdomen or thighs.</description>
    <arm_group_label>Active treatment</arm_group_label>
    <arm_group_label>Placebo treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Fat graft</intervention_name>
    <description>30mL harvested lipoaspirate is injected at the affected axillary site.</description>
    <arm_group_label>Active treatment</arm_group_label>
    <other_name>lipotransfer</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Sham graf (Saline injection)</intervention_name>
    <description>30mL saline is injected at the affected axillary site.</description>
    <arm_group_label>Placebo treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Stem cell injection</intervention_name>
    <description>4mL stem cell suspension injected at the affected axillary site.</description>
    <arm_group_label>Active treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Saline injection</intervention_name>
    <description>4mL saline injected at the affected axillary site.</description>
    <arm_group_label>Placebo treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Unilateral arm lymphedema secondary to breast cancer treatment including lymph node&#xD;
             dissection.&#xD;
&#xD;
          -  Cancer free for at least 1 year&#xD;
&#xD;
          -  The patient understands the nature and purpose of this study and the study procedures&#xD;
             and has signed informed consent.&#xD;
&#xD;
          -  The opposite upper extremity is healthy (no lymphedema).&#xD;
&#xD;
          -  ASA score of 1 or 2.&#xD;
&#xD;
          -  The patient is able to read, understand, and complete Danish questionnaires.&#xD;
&#xD;
          -  Pitting lymphedema ISL grade 1 or 2.&#xD;
&#xD;
          -  A minimum circumference difference of 2cm or a minimum volume difference of 200mL.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or lactating.&#xD;
&#xD;
          -  Bilateral lymphedema&#xD;
&#xD;
          -  Current or previous malignancies other than breast cancer.&#xD;
&#xD;
          -  Insulin-dependent diabetes.&#xD;
&#xD;
          -  Diagnosed with any form of psychotic disorder, which may impact study participation.&#xD;
&#xD;
          -  Not ceased smoking during treatment.&#xD;
&#xD;
          -  Active implantables (e.g. pacemaker or neurostimulator)&#xD;
&#xD;
          -  Unrealistic treatment expectations.&#xD;
&#xD;
          -  Known hepatitis, HIV or syphilis infection.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jens A Sørensen, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Department of Plastic Surgery, Odense University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Plastic and Reconstructive Surgery</name>
      <address>
        <city>Odense</city>
        <zip>5000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>November 12, 2018</study_first_submitted>
  <study_first_submitted_qc>December 14, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 17, 2018</study_first_posted>
  <last_update_submitted>June 24, 2021</last_update_submitted>
  <last_update_submitted_qc>June 24, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 25, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Odense University Hospital</investigator_affiliation>
    <investigator_full_name>Mads Gustaf Jørgensen</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphedema</mesh_term>
    <mesh_term>Breast Cancer Lymphedema</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03776721
org study id: S-20180117
nct id: NCT03776721
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: All patients undergo the same liposuction procedure. During general anesthesia, patients are randomized to either fat grafting or sham grafting with saline injection to the axilla. After stem cell suspension, patients receive either stem cell or saline injection depending on randomization using masked syringes.
Participants are blinded, care providers postoperatively are blinded, primary investigator is blinded and all outcome assessors are blinded. The surgeon performing the liposuction and the stem-cell staff are unblinded.
measure: Change in arm volume
time frame: Baseline, 3, 6, 9 and 12 months
description: Assessed using clinical circumference measurement
measure: Safety of treatments: Assessed by asking the patient at each visit
time frame: Baseline, 3, 6, 9 and 12 months
description: Any side effects to treatments. Assessed by asking the patient at each visit.
measure: Subjective changes assessed using the LYMPH-ICF (Lymphoedema Functioning, Disability and Health) questionaire
time frame: Baseline, 3, 6, 9 and 12 months
description: Subjective change of lymphedema assessed by questionnaire. Range: 0-100. 100 being the most bothered.
measure: Subjective changes assessed using DASH (DISABILITIES OF THE ARM, SHOULDER AND HAND) questionaire
time frame: Baseline, 3, 6, 9 and 12 months
description: Subjective change of lymphedema assessed by questionnaire. Range: 1-5. 5 being the most bothered
measure: Subjective changes assessed using SF-36 questionnaire
time frame: Baseline, 3, 6, 9 and 12 months
description: Subjective change of quality of life assessed by questionnaire. Range: 0-100. 0 being the most bothered.
measure: Change in lymph drainage
time frame: Baseline and 12 months
description: Change in lymph drainage assessed by indocyanine-green lymphangiography
measure: Change in conservative lymphedema treatment
time frame: Baseline, 3, 6, 9 and 12 months
description: Change in use or type of conservative lymphedema treatments
measure: Change in adverse lymphedema-related events
time frame: Baseline, 3, 6, 9 and 12 months
description: Change in infection rates and sick-days due to lymphedema.
measure: Change in L-DEX score (bioimpedance)
time frame: Baseline, 3, 6, 9 and 12 months
description: 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.
measure: Change in weight and arm tissue composition
time frame: Baseline, 3, 6, 9 and 12 months
description: Assessed using dual energy x-ray absorptiometry (DXA) scan. Change in values from baseline.
arm group label: Active treatment
arm group type: Experimental
arm group label: Placebo treatment
arm group type: Placebo Comparator
intervention type: Procedure
intervention name: Liposuction
description: Liposuction is performed on the abdomen or thighs.
arm group label: Active treatment
arm group label: Placebo treatment
intervention type: Procedure
intervention name: Fat graft
description: 30mL harvested lipoaspirate is injected at the affected axillary site.
arm group label: Active treatment
other name: lipotransfer
intervention type: Procedure
intervention name: Sham graf (Saline injection)
description: 30mL saline is injected at the affected axillary site.
arm group label: Placebo treatment
intervention type: Biological
intervention name: Stem cell injection
description: 4mL stem cell suspension injected at the affected axillary site.
arm group label: Active treatment
intervention type: Procedure
intervention name: Saline injection
description: 4mL saline injected at the affected axillary site.
arm group label: Placebo treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jens A Sørensen, MD, PhD
role: Study Chair
affiliation: Department of Plastic Surgery, Odense University Hospital
facility: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: Odense University Hospital
investigator full name: Mads Gustaf Jørgensen
investigator title: Principal Investigator
mesh term: Lymphedema
mesh term: Breast Cancer Lymphedema