<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/NCT03292198</url>
  </required_header>
  <id_info>
    <org_study_id>1070741-1</org_study_id>
    <nct_id>NCT03292198</nct_id>
  </id_info>
  <brief_title>Subclinical Lymphedema Treatment Study</brief_title>
  <acronym>SLT</acronym>
  <official_title>Treatment Indications for Breast Cancer-related Subclinical Lymphedema Identified Through a Bioimpedance Surveillance Model</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mercy Research</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Mercy Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>St. Louis Men's Group Against Cancer</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>ImpediMed Limited</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Juzo USA</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Mercy Research</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary Objective&#xD;
&#xD;
        -  To compare the effectiveness of 2 treatment protocols for patients with breast&#xD;
           cancer-related subclinical lymphedema identified through bioimpedance spectroscopy,&#xD;
           L-dex scores&#xD;
&#xD;
      Secondary Objectives&#xD;
&#xD;
        -  To determine the necessary duration of intervention to reverse L-dex scores back to a&#xD;
           normal range in patients with breast cancer-related subclinical lymphedema&#xD;
&#xD;
        -  To determine the time elapsed post-surgically to the development of subclinical&#xD;
           lymphedema identified by bioimpedance spectroscopy, L-dex scores&#xD;
&#xD;
        -  To identify risk factors for the development of subclinical lymphedema in patients with&#xD;
           breast cancer&#xD;
&#xD;
        -  To identify factors associated with the progression to clinical lymphedema following&#xD;
           treatment of subclinical lymphedema as identified by bioimpedance spectroscopy, L-dex&#xD;
           scores&#xD;
&#xD;
      Women with breast cancer diagnoses and planned axillary lymph node procedures will receive&#xD;
      pre-operative screening of arm volume with bioimpedance, which will capture baseline&#xD;
      measurements. Then, subjects will undergo periodic screenings for the first 3 years following&#xD;
      surgery. If a significant change in volume compared to baseline is detected with&#xD;
      bioimpedance, subjects will be randomized to 1 of 2 treatment groups. The outcomes of 2&#xD;
      treatment protocols will be compared. Additionally, subjects will be screened each week&#xD;
      during their treatment interventions to determine the necessary quantity of intervention&#xD;
      before L-dex scores normalize.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Lymphedema is an accumulation of fluid in the interstitial tissues resulting from an&#xD;
      impairment of the normal lymphatic drainage of the affected region. Lymphedema is often a&#xD;
      side effect of breast cancer treatments such as axillary lymph node surgery and radiation, as&#xD;
      these procedures are damaging to the lymphatic structures. Due to poor awareness of the&#xD;
      condition, minimal education is given to patients about their risk for lymphedema as a result&#xD;
      of cancer treatments. With inconsistent diagnostic methods, many cases of breast&#xD;
      cancer-related lymphedema are diagnosed after the condition has progressed to its&#xD;
      irreversible and chronic form, i.e. clinical lymphedema.&#xD;
&#xD;
      Bioimpedance spectroscopy (BIS) uses a low frequency electrical current to assess&#xD;
      extracellular fluid of the limbs. BIS has proven to be a sensitive and specific tool for&#xD;
      detecting subclinical lymphedema (Stage 0) and has been validated in its use within a&#xD;
      surveillance model. Recent literature supports the use of a surveillance model to identify&#xD;
      breast cancer-related subclinical lymphedema to allow for early intervention and improved&#xD;
      patient outcomes.&#xD;
&#xD;
      Despite the growing body of evidence supporting the importance of early identification of&#xD;
      lymphedema in the subclinical stage, there is limited evidence to guide treatment of this&#xD;
      patient population. Treatment parameters for subclinical lymphedema stem primarily from a&#xD;
      study by Stout et al. indicating that a short compression trial (mean duration of 4.4 weeks)&#xD;
      of 20-30 mmHg garments effectively treated subclinical lymphedema identified by perometry by&#xD;
      preventing progression to late-stage lymphedema.&#xD;
&#xD;
      Surveillance of arm volume will be performed using bioimpedance spectroscopy (BIS) testing&#xD;
      with the Impedimed® L-dex U400. Subjects will receive BIS testing (1) pre-operatively, (2)&#xD;
      post-operatively at 6 weeks, (3) 3 months, (4) 6 months, (5) 12 months, (6) 18 months, (7) 24&#xD;
      months, and (8) 36 months. The outcome measure will be the L-dex score.&#xD;
&#xD;
      Only subjects who have an abnormal result will be enrolled in the experimental portion of the&#xD;
      study. If an L-dex score is abnormal (defined by a change of +7 units from her pre-operative&#xD;
      baseline), the subject is determined to exhibit subclinical lymphedema. As a result, these&#xD;
      subjects will be randomized into one of two intervention groups. The group receiving only&#xD;
      compression intervention will be referred to as the compression group (CG). The group&#xD;
      receiving Manual Lymphatic Drainage (MLD) and compression will be referred to as the therapy&#xD;
      group (TG).&#xD;
&#xD;
      Subjects will be followed through screenings for a maximum of 3 years post-surgically.&#xD;
&#xD;
      The investigators hope that this study will take the next step in the surveillance model by&#xD;
      answering questions about how patients with subclinical lymphedema should be clinically&#xD;
      managed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">April 1, 2018</start_date>
  <completion_date type="Anticipated">December 2025</completion_date>
  <primary_completion_date type="Anticipated">December 2025</primary_completion_date>
  <phase>N/A</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>L-dex scores</measure>
    <time_frame>3 years post-operatively</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">267</enrollment>
  <condition>Breast Cancer-related Subclinical Lymphedema</condition>
  <arm_group>
    <arm_group_label>Compression Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects in the Compression Group will wear 20-30 mmHg sleeves and gauntlets daily for a maximum of 4 weeks. L-dex will be performed at the end of each week. If the L-dex score has reversed back into normal range, intervention (garment wearing) will be discontinued and the subject will resume the surveillance schedule of screenings. If the L-dex score is still abnormal, garment wearing continues. If L-dex score is abnormal even at the end of the 4 weeks, the subject will be removed from the study and referred to standard lymphedema therapy.&#xD;
An abnormal L-dex is defined by 7 or more units change compared to the subject's pre-surgical baseline.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Therapy Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects in the Therapy Group will wear 20-30 mmHg sleeves and gauntlets daily and receive Manual Lymphatic Drainage 3x/week for a maximum of 4 weeks. L-dex will be performed at the end of each week. If the L-dex score has reversed back into normal range, intervention will be discontinued and the subject will resume the surveillance schedule of screenings. If the L-dex score is abnormal, intervention continues. If L-dex score is abnormal even at the end of the 4 weeks, the subject will be removed from the study and referred to standard lymphedema therapy.&#xD;
An abnormal L-dex is defined by 7 or more units change compared to the subject's pre-surgical baseline.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>20-30 mmHg compression sleeve and gauntlet</intervention_name>
    <description>Compression garments are Juzo Soft, circular knit. Most will be off-the-shelf sizing, but custom when necessary.&#xD;
Garment fittings will be performed by Certified Lymphedema Therapists.</description>
    <arm_group_label>Compression Group</arm_group_label>
    <arm_group_label>Therapy Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Manual Lymphatic Drainage</intervention_name>
    <description>Manual Lymphatic Drainage (MLD) is a gentle skin-stretch massage that stimulates the lymphatic system and assists in creating collateral drainage pathways out of non-intact (damaged) lymphatic territories. MLD is a critical part of Complete Decongestive Therapy (CDT), which is accepted as the international standard of care in the treatment of lymphedema.&#xD;
The MLD sessions will be performed by 2 Certified Lymphedema Therapists, Megan Klote and Sarah Stolker, both trained through the Norton School of Lymphatic Therapy. The therapists have completed reliability meetings regarding MLD sequencing and techniques.</description>
    <arm_group_label>Therapy Group</arm_group_label>
    <other_name>MLD</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        New diagnosis of breast cancer, Female, 18 years of age or older, Upcoming unilateral&#xD;
        axillary lymph node procedure (biopsy or dissection), Able to provide informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Pre-existing diagnosis of lymphedema, as diagnosed by physician, History of axillary lymph&#xD;
        node procedure, including biopsy, dissection, or radiation to, Pregnancy, Pacemaker or&#xD;
        other implanted electrical device, Stage 4-5 kidney disease, Severe liver disease, Active&#xD;
        infection, Acute Deep Vein Thrombosis, Unmanaged congestive heart failure or a cardiac&#xD;
        event in the past 6 months, Prisoners&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Megan T Klote, DPT, CLT-LANA</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mercy Research</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mercy David C. Pratt Cancer Center</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>September 21, 2017</study_first_submitted>
  <study_first_submitted_qc>September 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <last_update_submitted>January 9, 2023</last_update_submitted>
  <last_update_submitted_qc>January 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mercy Research</investigator_affiliation>
    <investigator_full_name>Megan Klote</investigator_full_name>
    <investigator_title>Doctor of Physical Therapy, Certified Lymphedema Therapist - LANA</investigator_title>
  </responsible_party>
  <keyword>Subclinical lymphedema</keyword>
  <keyword>bioimpedance</keyword>
  <keyword>breast cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Lymphedema</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03292198
org study id: 1070741-1
nct id: NCT03292198
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Primary Objective

        -  To compare the effectiveness of 2 treatment protocols for patients with breast
           cancer-related subclinical lymphedema identified through bioimpedance spectroscopy,
           L-dex scores

      Secondary Objectives

        -  To determine the necessary duration of intervention to reverse L-dex scores back to a
           normal range in patients with breast cancer-related subclinical lymphedema

        -  To determine the time elapsed post-surgically to the development of subclinical
           lymphedema identified by bioimpedance spectroscopy, L-dex scores

        -  To identify risk factors for the development of subclinical lymphedema in patients with
           breast cancer

        -  To identify factors associated with the progression to clinical lymphedema following
           treatment of subclinical lymphedema as identified by bioimpedance spectroscopy, L-dex
           scores

      Women with breast cancer diagnoses and planned axillary lymph node procedures will receive
      pre-operative screening of arm volume with bioimpedance, which will capture baseline
      measurements. Then, subjects will undergo periodic screenings for the first 3 years following
      surgery. If a significant change in volume compared to baseline is detected with
      bioimpedance, subjects will be randomized to 1 of 2 treatment groups. The outcomes of 2
      treatment protocols will be compared. Additionally, subjects will be screened each week
      during their treatment interventions to determine the necessary quantity of intervention
      before L-dex scores normalize.
Lymphedema is an accumulation of fluid in the interstitial tissues resulting from an
      impairment of the normal lymphatic drainage of the affected region. Lymphedema is often a
      side effect of breast cancer treatments such as axillary lymph node surgery and radiation, as
      these procedures are damaging to the lymphatic structures. Due to poor awareness of the
      condition, minimal education is given to patients about their risk for lymphedema as a result
      of cancer treatments. With inconsistent diagnostic methods, many cases of breast
      cancer-related lymphedema are diagnosed after the condition has progressed to its
      irreversible and chronic form, i.e. clinical lymphedema.

      Bioimpedance spectroscopy (BIS) uses a low frequency electrical current to assess
      extracellular fluid of the limbs. BIS has proven to be a sensitive and specific tool for
      detecting subclinical lymphedema (Stage 0) and has been validated in its use within a
      surveillance model. Recent literature supports the use of a surveillance model to identify
      breast cancer-related subclinical lymphedema to allow for early intervention and improved
      patient outcomes.

      Despite the growing body of evidence supporting the importance of early identification of
      lymphedema in the subclinical stage, there is limited evidence to guide treatment of this
      patient population. Treatment parameters for subclinical lymphedema stem primarily from a
      study by Stout et al. indicating that a short compression trial (mean duration of 4.4 weeks)
      of 20-30 mmHg garments effectively treated subclinical lymphedema identified by perometry by
      preventing progression to late-stage lymphedema.

      Surveillance of arm volume will be performed using bioimpedance spectroscopy (BIS) testing
      with the Impedimed® L-dex U400. Subjects will receive BIS testing (1) pre-operatively, (2)
      post-operatively at 6 weeks, (3) 3 months, (4) 6 months, (5) 12 months, (6) 18 months, (7) 24
      months, and (8) 36 months. The outcome measure will be the L-dex score.

      Only subjects who have an abnormal result will be enrolled in the experimental portion of the
      study. If an L-dex score is abnormal (defined by a change of +7 units from her pre-operative
      baseline), the subject is determined to exhibit subclinical lymphedema. As a result, these
      subjects will be randomized into one of two intervention groups. The group receiving only
      compression intervention will be referred to as the compression group (CG). The group
      receiving Manual Lymphatic Drainage (MLD) and compression will be referred to as the therapy
      group (TG).

      Subjects will be followed through screenings for a maximum of 3 years post-surgically.

      The investigators hope that this study will take the next step in the surveillance model by
      answering questions about how patients with subclinical lymphedema should be clinically
      managed.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: L-dex scores
time frame: 3 years post-operatively
arm group label: Compression Group
arm group type: Active Comparator
description: Subjects in the Compression Group will wear 20-30 mmHg sleeves and gauntlets daily for a maximum of 4 weeks. L-dex will be performed at the end of each week. If the L-dex score has reversed back into normal range, intervention (garment wearing) will be discontinued and the subject will resume the surveillance schedule of screenings. If the L-dex score is still abnormal, garment wearing continues. If L-dex score is abnormal even at the end of the 4 weeks, the subject will be removed from the study and referred to standard lymphedema therapy.
An abnormal L-dex is defined by 7 or more units change compared to the subject's pre-surgical baseline.
arm group label: Therapy Group
arm group type: Experimental
description: Subjects in the Therapy Group will wear 20-30 mmHg sleeves and gauntlets daily and receive Manual Lymphatic Drainage 3x/week for a maximum of 4 weeks. L-dex will be performed at the end of each week. If the L-dex score has reversed back into normal range, intervention will be discontinued and the subject will resume the surveillance schedule of screenings. If the L-dex score is abnormal, intervention continues. If L-dex score is abnormal even at the end of the 4 weeks, the subject will be removed from the study and referred to standard lymphedema therapy.
An abnormal L-dex is defined by 7 or more units change compared to the subject's pre-surgical baseline.
intervention type: Other
intervention name: 20-30 mmHg compression sleeve and gauntlet
description: Compression garments are Juzo Soft, circular knit. Most will be off-the-shelf sizing, but custom when necessary.
Garment fittings will be performed by Certified Lymphedema Therapists.
arm group label: Compression Group
arm group label: Therapy Group
intervention type: Other
intervention name: Manual Lymphatic Drainage
description: Manual Lymphatic Drainage (MLD) is a gentle skin-stretch massage that stimulates the lymphatic system and assists in creating collateral drainage pathways out of non-intact (damaged) lymphatic territories. MLD is a critical part of Complete Decongestive Therapy (CDT), which is accepted as the international standard of care in the treatment of lymphedema.
The MLD sessions will be performed by 2 Certified Lymphedema Therapists, Megan Klote and Sarah Stolker, both trained through the Norton School of Lymphatic Therapy. The therapists have completed reliability meetings regarding MLD sequencing and techniques.
arm group label: Therapy Group
other name: MLD
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Megan T Klote, DPT, CLT-LANA
role: Principal Investigator
affiliation: Mercy Research
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Mercy Research
investigator full name: Megan Klote
investigator title: Doctor of Physical Therapy, Certified Lymphedema Therapist - LANA
mesh term: Breast Neoplasms
mesh term: Lymphedema
sharing ipd: No