<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/NCT03041844</url>
  </required_header>
  <id_info>
    <org_study_id>1609004864</org_study_id>
    <nct_id>NCT03041844</nct_id>
  </id_info>
  <brief_title>Enhanced Ultrasound Treatment of Chronic Wounds With Monitoring of Healing and Quality of Life Outcomes</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>Drexel University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Temple University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Drexel University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the effect of low frequency, low intensity&#xD;
      ultrasound treatment on wound healing and health-related quality of life with a randomized&#xD;
      clinical trial of patients with venous ulcers or diabetic ulcers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The two most common types of chronic wounds are venous ulcers (VUs) and diabetic ulcers&#xD;
      (DUs). The investigators will conduct the first double-blind randomized controlled trial&#xD;
      (RCT) to test the effect of low-frequency, low-intensity (LFLI) ultrasound (US) on chronic&#xD;
      wound healing and health related quality of life (HRQOL) with high statistical confidence (α&#xD;
      &lt; 0.05, power &gt; 0.90, n=60 VUs, n=60 DUs). The investigators' approach combines this active&#xD;
      therapy with non-invasive diagnostic monitoring of wound hemodynamics throughout the&#xD;
      treatment cycle, and includes analysis of the impact of nutritional status and inflammation&#xD;
      on wound closure. There are several innovative aspects of this work. Specifically, (1) The&#xD;
      lightweight, battery-powered applicator is the first potentially wearable ultrasound wound&#xD;
      therapy device that is safe to apply for extended periods of time. (2) The applicator&#xD;
      actively promotes healing, which is fundamentally different from commercial ultrasonic&#xD;
      systems that remove necrotic tissue only. (3) The study approach will link LFLI US exposure&#xD;
      to changes in wound hemodynamics and HRQOL, which has the potential to enable personalized&#xD;
      medicine. (4) The analysis of patient nutritional and systemic inflammatory status may enable&#xD;
      further treatment customization by identifying those patients most likely to benefit from&#xD;
      LFLI US therapy. (5) The study approach incorporates both disease-specific and generic&#xD;
      measures of HRQOL, which is unique for a therapeutic ultrasound RCT.&#xD;
&#xD;
      The low-frequency, low-intensity (20 kiloHertz (kHz), &lt;100 milliWatt per square centimeter&#xD;
      (mW/cm2) spatial peak-temporal peak), portable ultrasound applicator is lightweight (&lt;25g)&#xD;
      and permits safe and clinically pragmatic wound treatment. The field parameters of the US&#xD;
      device were previously optimized for venous ulcers, and three recent pilot clinical human&#xD;
      studies (VUs: n=20, n=25; DUs: n=10) demonstrated that the treatment improved healing by 15%&#xD;
      per week compared to sham treatment. The investigators therefore anticipate that our&#xD;
      treatment will accelerate closure of chronic wounds, and hypothesize that (1) LFLI US will&#xD;
      improve generic and disease-specific HRQOL scores, (2) LFLI US will activate beneficial&#xD;
      changes in the microvasculature of the wound and surrounding tissue, and (3) individuals with&#xD;
      poor nutrition and high levels of inflammation will have delayed wound healing.&#xD;
&#xD;
      The specific aims are to: (1) Assess the effect of LFLI US on VUs and DUs by measuring wound&#xD;
      closure as a primary endpoint and generic and disease-specific HRQOL as secondary endpoints.&#xD;
      (2) Monitor the effects of LFLI US on wound perfusion and oxygenation using non-invasive&#xD;
      optical methods, and (3) Determine the impact of nutritional status and inflammation on&#xD;
      closure of DUs and VUs. Overall, this work will validate LFLI US as a safe, portable, and&#xD;
      cost-effective therapy for chronic wounds. This is important because new therapies and&#xD;
      improved clinical paradigms for wound management are urgently needed. Over the long-term, the&#xD;
      study findings may enable the development of personalized wound treatment regimens across&#xD;
      care settings.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>January 2017</start_date>
  <completion_date type="Anticipated">March 2023</completion_date>
  <primary_completion_date type="Actual">March 2022</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in wound size</measure>
    <time_frame>4 weeks</time_frame>
    <description>Percentage change in wound size over 4 weeks</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Wound closure</measure>
    <time_frame>16 weeks</time_frame>
    <description>Complete wound closure at 16 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health Related Quality of Life (HRQOL)</measure>
    <time_frame>16 weeks, then 6 and 12 months after last treatment</time_frame>
    <description>Short form health survey will be administered to assess changes in HRQOL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Wound Quality of Life (WQOL)</measure>
    <time_frame>16 weeks</time_frame>
    <description>Health survey will be administered to assess changes in wound-related HRQOL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Wound oxyhemoglobin concentration change</measure>
    <time_frame>16 weeks</time_frame>
    <description>Change in wound oxyhemoglobin concentration per week, measured with diffuse near infrared spectroscopy (DNIRS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Microcirculatory blood flow index change</measure>
    <time_frame>16 weeks</time_frame>
    <description>Change in microcirculatory blood flow index per week, measured with diffuse correlation spectroscopy (DCS)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">72</enrollment>
  <condition>Diabetic Foot Ulcer</condition>
  <condition>Venous Ulcer</condition>
  <arm_group>
    <arm_group_label>Low Frequency, Low Intensity Ultrasound</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Low Frequency, Low Intensity therapeutic ultrasound applied weekly for up to 16 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham Ultrasound</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Sham ultrasound applied weekly for up to 16 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Low Frequency, Low Intensity Ultrasound</intervention_name>
    <description>Therapeutic ultrasound (20 kHz, &lt;100 mW/cm2 spatial peak-temporal peak)</description>
    <arm_group_label>Low Frequency, Low Intensity Ultrasound</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham Applicator</intervention_name>
    <description>Sham ultrasound applicator</description>
    <arm_group_label>Sham Ultrasound</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Have a venous ulcer (VU) or diabetic ulcer (DU) that has been documented for at least&#xD;
             8 weeks without complete re-epithelialization and is larger than 0.75 cm2 in size.&#xD;
&#xD;
          -  VUs must be present on the lower extremities non-weight-bearing areas.&#xD;
&#xD;
          -  DUs must be present on the ankle or foot and be secondary to complications from&#xD;
             diabetes.&#xD;
&#xD;
          -  Patients with DUs must have a documented history of diabetes mellitus of at least six&#xD;
             months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  VUs secondary to any connective tissue disorder or blood dyscrasias.&#xD;
&#xD;
          -  Severe vascular insufficiency (ankle-brachial index lower than 0.75 or toe-brachial&#xD;
             index below 0.5).&#xD;
&#xD;
          -  Active, untreated infection&#xD;
&#xD;
          -  Acute deep venous thrombosis&#xD;
&#xD;
          -  Cutaneous malignancy present on the involved extremity&#xD;
&#xD;
          -  Active (or past 6 months) cancer treatment&#xD;
&#xD;
          -  Presence of both a diabetic ulcer and a venous ulcer on the same extremity&#xD;
&#xD;
          -  Known allergy to Tegaderm (a polyurethane dressing)&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  Individuals younger than 18 years of age regardless of emancipation status&#xD;
&#xD;
          -  Prisoners&#xD;
&#xD;
          -  Individuals unable to speak English, Spanish, or Mandarin&#xD;
&#xD;
          -  Adults unable to consent&#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>Peter A Lewin, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Drexel University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Temple University School of Podiatric Medicine</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>January 25, 2017</study_first_submitted>
  <study_first_submitted_qc>February 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 3, 2017</study_first_posted>
  <last_update_submitted>April 5, 2022</last_update_submitted>
  <last_update_submitted_qc>April 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>therapeutic ultrasound</keyword>
  <keyword>quality of life</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetic Foot</mesh_term>
    <mesh_term>Varicose Ulcer</mesh_term>
    <mesh_term>Foot Ulcer</mesh_term>
    <mesh_term>Ulcer</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03041844
org study id: 1609004864
nct id: NCT03041844
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
The purpose of this study is to evaluate the effect of low frequency, low intensity
      ultrasound treatment on wound healing and health-related quality of life with a randomized
      clinical trial of patients with venous ulcers or diabetic ulcers.
The two most common types of chronic wounds are venous ulcers (VUs) and diabetic ulcers
      (DUs). The investigators will conduct the first double-blind randomized controlled trial
      (RCT) to test the effect of low-frequency, low-intensity (LFLI) ultrasound (US) on chronic
      wound healing and health related quality of life (HRQOL) with high statistical confidence (α
      < 0.05, power > 0.90, n=60 VUs, n=60 DUs). The investigators' approach combines this active
      therapy with non-invasive diagnostic monitoring of wound hemodynamics throughout the
      treatment cycle, and includes analysis of the impact of nutritional status and inflammation
      on wound closure. There are several innovative aspects of this work. Specifically, (1) The
      lightweight, battery-powered applicator is the first potentially wearable ultrasound wound
      therapy device that is safe to apply for extended periods of time. (2) The applicator
      actively promotes healing, which is fundamentally different from commercial ultrasonic
      systems that remove necrotic tissue only. (3) The study approach will link LFLI US exposure
      to changes in wound hemodynamics and HRQOL, which has the potential to enable personalized
      medicine. (4) The analysis of patient nutritional and systemic inflammatory status may enable
      further treatment customization by identifying those patients most likely to benefit from
      LFLI US therapy. (5) The study approach incorporates both disease-specific and generic
      measures of HRQOL, which is unique for a therapeutic ultrasound RCT.

      The low-frequency, low-intensity (20 kiloHertz (kHz), <100 milliWatt per square centimeter
      (mW/cm2) spatial peak-temporal peak), portable ultrasound applicator is lightweight (<25g)
      and permits safe and clinically pragmatic wound treatment. The field parameters of the US
      device were previously optimized for venous ulcers, and three recent pilot clinical human
      studies (VUs: n=20, n=25; DUs: n=10) demonstrated that the treatment improved healing by 15%
      per week compared to sham treatment. The investigators therefore anticipate that our
      treatment will accelerate closure of chronic wounds, and hypothesize that (1) LFLI US will
      improve generic and disease-specific HRQOL scores, (2) LFLI US will activate beneficial
      changes in the microvasculature of the wound and surrounding tissue, and (3) individuals with
      poor nutrition and high levels of inflammation will have delayed wound healing.

      The specific aims are to: (1) Assess the effect of LFLI US on VUs and DUs by measuring wound
      closure as a primary endpoint and generic and disease-specific HRQOL as secondary endpoints.
      (2) Monitor the effects of LFLI US on wound perfusion and oxygenation using non-invasive
      optical methods, and (3) Determine the impact of nutritional status and inflammation on
      closure of DUs and VUs. Overall, this work will validate LFLI US as a safe, portable, and
      cost-effective therapy for chronic wounds. This is important because new therapies and
      improved clinical paradigms for wound management are urgently needed. Over the long-term, the
      study findings may enable the development of personalized wound treatment regimens across
      care settings.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in wound size
time frame: 4 weeks
description: Percentage change in wound size over 4 weeks
measure: Wound closure
time frame: 16 weeks
description: Complete wound closure at 16 weeks
measure: Health Related Quality of Life (HRQOL)
time frame: 16 weeks, then 6 and 12 months after last treatment
description: Short form health survey will be administered to assess changes in HRQOL
measure: Wound Quality of Life (WQOL)
time frame: 16 weeks
description: Health survey will be administered to assess changes in wound-related HRQOL
measure: Wound oxyhemoglobin concentration change
time frame: 16 weeks
description: Change in wound oxyhemoglobin concentration per week, measured with diffuse near infrared spectroscopy (DNIRS)
measure: Microcirculatory blood flow index change
time frame: 16 weeks
description: Change in microcirculatory blood flow index per week, measured with diffuse correlation spectroscopy (DCS)
arm group label: Low Frequency, Low Intensity Ultrasound
arm group type: Experimental
description: Low Frequency, Low Intensity therapeutic ultrasound applied weekly for up to 16 weeks.
arm group label: Sham Ultrasound
arm group type: Sham Comparator
description: Sham ultrasound applied weekly for up to 16 weeks.
intervention type: Device
intervention name: Low Frequency, Low Intensity Ultrasound
description: Therapeutic ultrasound (20 kHz, <100 mW/cm2 spatial peak-temporal peak)
arm group label: Low Frequency, Low Intensity Ultrasound
intervention type: Device
intervention name: Sham Applicator
description: Sham ultrasound applicator
arm group label: Sham Ultrasound
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Peter A Lewin, PhD
role: Principal Investigator
affiliation: Drexel University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Diabetic Foot
mesh term: Varicose Ulcer
mesh term: Foot Ulcer
mesh term: Ulcer
sharing ipd: Undecided