xml: <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/NCT06038864</url>
    </required_header>
    <id_info>
      <org_study_id>s66033-aim4</org_study_id>
      <nct_id>NCT06038864</nct_id>
    </id_info>
    <brief_title>Development of a Clinical Screening, Diagnostic and Evaluation Tool for Patients With Lower Limb Lymphedema: Aim 4</brief_title>
    <acronym>EvaLymph-Leg4</acronym>
    <official_title>Development of a Clinical Screening, Diagnostic and Evaluation Tool for Patients With Lower Limb Lymphedema: Development of an Evaluation Set for Patients With LLL</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>KU Leuven</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Universitaire Ziekenhuizen KU Leuven</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Nij Smellinghe Hospital Drachten</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>KU Leuven</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>
    </oversight_info>
    <brief_summary>
      <textblock>
        Research investigating measurement properties for evaluating the decongestive treatment&#xD;
        effect on different edema characteristics (e.g. water volume, hardness of the skin, water&#xD;
        content,..) at the level of the lower limbs is missing. Information about the clinical&#xD;
        relevant change criteria after treatment for nearly all these edema characteristics, is not&#xD;
        present and requires investigation.&#xD;
  &#xD;
        To assess the merits of each treatment in a reproducible manner, a reliable way of measuring&#xD;
        limb volume and other edema characteristics must be established, as the evaluation of&#xD;
        treatment effects without appropriate tools might lead to biased treatment effects.&#xD;
  &#xD;
        First of all, in clinical practice, it is of utmost importance to know which edema&#xD;
        characteristics need to be evaluated in order to assess the clinical evolution of a patient&#xD;
        with lymphedema during and after treatment. Secondly, in order to draw proper conclusions&#xD;
        about the treatment effect, it is necessary that to know from which criterion (or cut-off&#xD;
        value) one can speak of a real clinical change for a certain lymphedema characteristic. Given&#xD;
        that the edema characteristics that are most responsive to treatment and their corresponding&#xD;
        criteria for clinically significant and relevant changes at the lower limbs have never been&#xD;
        investigated before, the need for this research is high.&#xD;
  &#xD;
        Therefore, the research questions in this study are: Which measurement tool(s) are able to&#xD;
        detect clinically relevant changes in the lymphedema characteristics after the intensive&#xD;
        treatment and during the maintenance treatment? When can a clinician speak of a clinically&#xD;
        relevant change?&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">April 1, 2024</start_date>
    <completion_date type="Anticipated">December 1, 2024</completion_date>
    <primary_completion_date type="Anticipated">November 1, 2024</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Sensitivity of measurement methods</measure>
      <time_frame>1 month</time_frame>
      <description>Sensitivity of measurement methods (resulting from aim 1:NCT05269264) in the evaluation of the treatment effect over time in patients with unilateral and bilateral LLL.&#xD;
  Patients will be evaluated twice with 1 month in between.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Specificity of measurement methods</measure>
      <time_frame>1 month</time_frame>
      <description>Specificity of measurement methods (resulting from aim 1:NCT05269264) in the evaluation of the treatment effect over time in patients with unilateral and bilateral LLL.&#xD;
  Patients will be evaluated twice with 1 month in between.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Diagnostic accuracy of measurement methods</measure>
      <time_frame>1 month</time_frame>
      <description>Diagnostic accuracy (in terms of area under the curve using a ROC curve, as well as sensitivity and specificity) of measurement methods (resulting from aim 1:NCT05269264) in the evaluation of the treatment effect over time in patients with unilateral and bilateral LLL.&#xD;
  Patients will be evaluated twice with 1 month in between.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Lymphedema volume after 4 weeks of intensive DLT in patients with unilateral and bilateral LLL</measure>
      <time_frame>1 month</time_frame>
      <description>Evaluation of different outcome parameters in the patients from the 'intensive group' with unilateral LLL and patients with bilateral LLL:&#xD;
  Lymphedema volume (foot, leg)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hardness of skin after 4 weeks of intensive DLT in patients with unilateral and bilateral LLL</measure>
      <time_frame>1 month</time_frame>
      <description>Evaluation of different outcome parameters in the patients from the 'intensive group' with unilateral LLL and patients with bilateral LLL:&#xD;
  skin hardness test at the level of the foot, leg and midline region. Skin is palpated with thumb and index (and, if possible, compared to the contralateral side) Outcome: If skin is hardened; yes(1), otherwise; no(0)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Piiting status after 4 weeks f intensive DLT in patients with unilateral and bilateral LLL</measure>
      <time_frame>1 month</time_frame>
      <description>Evaluation of different outcome parameters in the patients from the 'intensive group' with unilateral LLL and patients with bilateral LLL:&#xD;
  Pitting test at the level of the foot, leg and midline region;&#xD;
  The grading of edema is determined by pit depth (measured visually) and recovery time from grade 0-3. The scale is used to rate the severity and the scores are as follows:&#xD;
  - Grade 0: No clinical edema- Grade 1: Slight pitting (up to 2 mm depth) - Grade 2: Moderate pitting (2-5 mm) - Grade 3: Noticeably deep pit (&gt;5 mm)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Skinfold thickness after 4 weeks of intensive DLT in patients with unilateral and bilateral LLL</measure>
      <time_frame>1 month</time_frame>
      <description>Evaluation of different outcome parameters in the patients from the 'intensive group' with unilateral LLL and patients with bilateral LLL:&#xD;
  Skinfold test at the level of the foot, leg and midline region:&#xD;
  Skin and subcutaneous tissue is lifted between thumb and index(and, if possible, compared to the contralateral side) Outcome:If skinfold is increased; yes(1), otherwise; no(0)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Extracellullar fluid after 4 weeks of intensive DLT in patients with unilateral and bilateral LLL</measure>
      <time_frame>1 month</time_frame>
      <description>Evaluation of different outcome parameters (ECW ratio, total body water, body water left/right leg, ICW total/left/right, ECW total/left/right, phase angle total/left/right, impedance at 5 kHz) in the patients from the 'intensive group' with unilateral LLL and patients with bilateral LLL:&#xD;
  Extracellular fluid</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Problems in functioning after 4 weeks of intensive DLT in patients with unilateral and bilateral LLL</measure>
      <time_frame>1 month</time_frame>
      <description>Disease-specific QoL (i.e. problems in functioning will be evaluated with the Lymph-ICF-LL.&#xD;
  The Lymph-ICF-LL is a descriptive, evaluative tool containing 28 questions about impairments in function, activity limitations, and participation restrictions in patients with lower limb lymphedema. The questionnaire has 5 domains: physical function, mental function, general tasks/household activities, mobility activities, and life domains/social life.</description>
    </secondary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">120</enrollment>
    <condition>Lower Limb Lymphedema</condition>
    <arm_group>
      <arm_group_label>Intensive group</arm_group_label>
      <description>Patients with lower limb lymphoedema planned for intensive treatment</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Maintenance group</arm_group_label>
      <description>Patients with stable lower limb lymphoedema who are in the maintenance phase (at least 3 months)</description>
    </arm_group>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>2 clinical evaluations with 1 month in between</intervention_name>
      <description>Patients will be evaluated twice with all evaluation methods selected by the international expert group (cfr. aim 1) showing sufficient reliability and feasibility in the patient group with LLL from aim 1</description>
      <arm_group_label>Intensive group</arm_group_label>
      <arm_group_label>Maintenance group</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          Intensive treatment group: Patients planned to start with intensive decongestive lymphatic&#xD;
          therapy at one or both legs.&#xD;
  &#xD;
          Maintenance treatment group: patienst who have ended their intensive treatment phase at&#xD;
          least 3 months ago (= currently receiving maintenance decongestive lymphatic therapy)&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Intensive treatment group&#xD;
  &#xD;
                 -  Unilateral or bilateral, primary or secondary LLL&#xD;
  &#xD;
                 -  No active metastases&#xD;
  &#xD;
                 -  If cancer-related lymphedema, time interval since surgery/ radiotherapy/&#xD;
                    chemotherapy is ≥3 months&#xD;
  &#xD;
                 -  Objective diagnosis of lymphedema: ≥ 5% volume difference OR ≥ 2 minor/ 1 major&#xD;
                    criteria on lymphoscintigraphy OR presence of ICG dermal backflow&#xD;
  &#xD;
                 -  Age ≥ 18 years&#xD;
  &#xD;
                 -  Able to read, understand and speak Dutch&#xD;
  &#xD;
                 -  Planned to start with intensive decongestive lymphatic therapy at one or both&#xD;
                    legs&#xD;
  &#xD;
            -  Maintenance treatment group&#xD;
  &#xD;
                 -  See inclusion criteria 'intensive treatment group'&#xD;
  &#xD;
                 -  But: instead of patients planned to start with intensive lymphatic therapy,&#xD;
                    patients of this group should have ended their intensive treatment phase at least&#xD;
                    3 months ago (= currently receiving maintenance decongestive lymphatic therapy)&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Pregnant participants&#xD;
  &#xD;
            -  Presence of chronic venous insufficiency C4, C5, C6; deep venous thrombosis;&#xD;
               post-thrombotic syndrome&#xD;
  &#xD;
            -  Presence of skin infections of wounds at the level of the lower limbs at the moment of&#xD;
               inclusion&#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>Tessa De Vrieze, Dr.</last_name>
      <role>Principal Investigator</role>
      <affiliation>KU Leuven</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Tessa De Vrieze, Dr.</last_name>
      <phone>003216345006</phone>
      <email>tessa.devrieze@kuleuven.be</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Nele Devoogdt, Prof. Dr.</last_name>
      <phone>0032 16 342515</phone>
      <email>nele.devoogdt@kuleuven.be</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>University Hospitals of Leuven</name>
        <address>
          <city>Leuven</city>
          <zip>3000</zip>
          <country>Belgium</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Nij Smellinghe Hospital</name>
        <address>
          <city>Drachten</city>
          <zip>9202</zip>
          <country>Netherlands</country>
        </address>
      </facility>
      <contact>
        <last_name>Ad Hendrickx, PhD</last_name>
        <email>a.hendrickx@nijsmellinghe.nl</email>
      </contact>
      <contact_backup>
        <last_name>Robert Damstra, PhD</last_name>
        <email>r.damstra@nijsmellinghe.nl</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>Belgium</country>
      <country>Netherlands</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 4, 2023</study_first_submitted>
    <study_first_submitted_qc>September 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 15, 2023</study_first_posted>
    <last_update_submitted>September 8, 2023</last_update_submitted>
    <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>KU Leuven</investigator_affiliation>
      <investigator_full_name>Tessa De Vrieze</investigator_full_name>
      <investigator_title>Principal investigator</investigator_title>
    </responsible_party>
    <keyword>lymphedema</keyword>
    <keyword>measurement</keyword>
    <keyword>clinical evaluation</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Lymphedema</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06038864
  org study id: s66033-aim4
  nct id: NCT06038864
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Research investigating measurement properties for evaluating the decongestive treatment
        effect on different edema characteristics (e.g. water volume, hardness of the skin, water
        content,..) at the level of the lower limbs is missing. Information about the clinical
        relevant change criteria after treatment for nearly all these edema characteristics, is not
        present and requires investigation.
  
        To assess the merits of each treatment in a reproducible manner, a reliable way of measuring
        limb volume and other edema characteristics must be established, as the evaluation of
        treatment effects without appropriate tools might lead to biased treatment effects.
  
        First of all, in clinical practice, it is of utmost importance to know which edema
        characteristics need to be evaluated in order to assess the clinical evolution of a patient
        with lymphedema during and after treatment. Secondly, in order to draw proper conclusions
        about the treatment effect, it is necessary that to know from which criterion (or cut-off
        value) one can speak of a real clinical change for a certain lymphedema characteristic. Given
        that the edema characteristics that are most responsive to treatment and their corresponding
        criteria for clinically significant and relevant changes at the lower limbs have never been
        investigated before, the need for this research is high.
  
        Therefore, the research questions in this study are: Which measurement tool(s) are able to
        detect clinically relevant changes in the lymphedema characteristics after the intensive
        treatment and during the maintenance treatment? When can a clinician speak of a clinically
        relevant change?
  observational model: Cohort
  time perspective: Prospective
  measure: Sensitivity of measurement methods
  time frame: 1 month
  description: Sensitivity of measurement methods (resulting from aim 1:NCT05269264) in the evaluation of the treatment effect over time in patients with unilateral and bilateral LLL.
  Patients will be evaluated twice with 1 month in between.
  measure: Specificity of measurement methods
  time frame: 1 month
  description: Specificity of measurement methods (resulting from aim 1:NCT05269264) in the evaluation of the treatment effect over time in patients with unilateral and bilateral LLL.
  Patients will be evaluated twice with 1 month in between.
  measure: Diagnostic accuracy of measurement methods
  time frame: 1 month
  description: Diagnostic accuracy (in terms of area under the curve using a ROC curve, as well as sensitivity and specificity) of measurement methods (resulting from aim 1:NCT05269264) in the evaluation of the treatment effect over time in patients with unilateral and bilateral LLL.
  Patients will be evaluated twice with 1 month in between.
  measure: Lymphedema volume after 4 weeks of intensive DLT in patients with unilateral and bilateral LLL
  time frame: 1 month
  description: Evaluation of different outcome parameters in the patients from the 'intensive group' with unilateral LLL and patients with bilateral LLL:
  Lymphedema volume (foot, leg)
  measure: Hardness of skin after 4 weeks of intensive DLT in patients with unilateral and bilateral LLL
  time frame: 1 month
  description: Evaluation of different outcome parameters in the patients from the 'intensive group' with unilateral LLL and patients with bilateral LLL:
  skin hardness test at the level of the foot, leg and midline region. Skin is palpated with thumb and index (and, if possible, compared to the contralateral side) Outcome: If skin is hardened; yes(1), otherwise; no(0)
  measure: Piiting status after 4 weeks f intensive DLT in patients with unilateral and bilateral LLL
  time frame: 1 month
  description: Evaluation of different outcome parameters in the patients from the 'intensive group' with unilateral LLL and patients with bilateral LLL:
  Pitting test at the level of the foot, leg and midline region;
  The grading of edema is determined by pit depth (measured visually) and recovery time from grade 0-3. The scale is used to rate the severity and the scores are as follows:
  - Grade 0: No clinical edema- Grade 1: Slight pitting (up to 2 mm depth) - Grade 2: Moderate pitting (2-5 mm) - Grade 3: Noticeably deep pit (>5 mm)
  measure: Skinfold thickness after 4 weeks of intensive DLT in patients with unilateral and bilateral LLL
  time frame: 1 month
  description: Evaluation of different outcome parameters in the patients from the 'intensive group' with unilateral LLL and patients with bilateral LLL:
  Skinfold test at the level of the foot, leg and midline region:
  Skin and subcutaneous tissue is lifted between thumb and index(and, if possible, compared to the contralateral side) Outcome:If skinfold is increased; yes(1), otherwise; no(0)
  measure: Extracellullar fluid after 4 weeks of intensive DLT in patients with unilateral and bilateral LLL
  time frame: 1 month
  description: Evaluation of different outcome parameters (ECW ratio, total body water, body water left/right leg, ICW total/left/right, ECW total/left/right, phase angle total/left/right, impedance at 5 kHz) in the patients from the 'intensive group' with unilateral LLL and patients with bilateral LLL:
  Extracellular fluid
  measure: Problems in functioning after 4 weeks of intensive DLT in patients with unilateral and bilateral LLL
  time frame: 1 month
  description: Disease-specific QoL (i.e. problems in functioning will be evaluated with the Lymph-ICF-LL.
  The Lymph-ICF-LL is a descriptive, evaluative tool containing 28 questions about impairments in function, activity limitations, and participation restrictions in patients with lower limb lymphedema. The questionnaire has 5 domains: physical function, mental function, general tasks/household activities, mobility activities, and life domains/social life.
  arm group label: Intensive group
  description: Patients with lower limb lymphoedema planned for intensive treatment
  arm group label: Maintenance group
  description: Patients with stable lower limb lymphoedema who are in the maintenance phase (at least 3 months)
  intervention type: Diagnostic Test
  intervention name: 2 clinical evaluations with 1 month in between
  description: Patients will be evaluated twice with all evaluation methods selected by the international expert group (cfr. aim 1) showing sufficient reliability and feasibility in the patient group with LLL from aim 1
  arm group label: Intensive group
  arm group label: Maintenance group
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Tessa De Vrieze, Dr.
  role: Principal Investigator
  affiliation: KU Leuven
  last name: Tessa De Vrieze, Dr.
  phone: 003216345006
  email: tessa.devrieze@kuleuven.be
  last name: Nele Devoogdt, Prof. Dr.
  phone: 0032 16 342515
  email: nele.devoogdt@kuleuven.be
  facility: 
  facility: 
  contact: 
  contact backup: 
  country: Belgium
  country: Netherlands
  responsible party type: Principal Investigator
  investigator affiliation: KU Leuven
  investigator full name: Tessa De Vrieze
  investigator title: Principal investigator
  mesh term: Lymphedema