<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/NCT03250533</url>
  </required_header>
  <id_info>
    <org_study_id>U1111-1143-0079</org_study_id>
    <nct_id>NCT03250533</nct_id>
  </id_info>
  <brief_title>Analysis of the Effects of LED Phototherapy and Electrical Stimulation in the Healing of Diabetic Ulcers</brief_title>
  <official_title>Analysis of the Effects of Phototherapy With Light-emitting Diodes (LED) and Electrical Stimulation in the Healing of Ulcers of Lower Diabetic Limbs: a Blind Controlled Randomized Clinical Test</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Sao Paulo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Sao Paulo</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>
      One of the important complications of DM is the diabetic foot that may present ulcers, which&#xD;
      result from multiple risk factors, being diabetic peripheral neuropathy and ischemia due to&#xD;
      peripheral vascular disease considered the main causes. In this way, the ulcers of the lower&#xD;
      extremities of diabetics, have a complex and long cicatrization process. Faced with this, the&#xD;
      treatment of chronic wounds is challenging, the diversity of treatments is great, however the&#xD;
      search for new modalities of effective therapeutic resources, scientifically proven and&#xD;
      financially feasible, that are available and easily accessible for clinical practice is still&#xD;
      desirable . The aim of this study was to evaluate the responses of phototherapy with light&#xD;
      emitting diodes (LED) and electrical stimulation with the fixed diphasic current (DF) in&#xD;
      ulcers of diabetic patients. Diabetic volunteers who present with chronic skin ulcers will&#xD;
      also be randomized (n = 13) to: Treatment group with LED 620 nm, Treatment group with LED 940&#xD;
      nm, Treatment group with fixed diphasic current and Control group. Interventions will occur&#xD;
      three times a week for 12 weeks and evaluations will occur on the 1st, 30th, 60th, and 90th&#xD;
      day of the intervention, followed by follow-up after 30 days of treatment completion.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background: Diabetes mellitus (DM) is a chronic disease currently considered a worldwide&#xD;
      epidemic and has become a major public health problem. One of the important complications of&#xD;
      DM is the diabetic foot that may present ulcers, which result from multiple risk factors,&#xD;
      being diabetic peripheral neuropathy and ischemia due to peripheral vascular disease&#xD;
      considered the main causes. In this way, the ulcers of the lower extremities of diabetics,&#xD;
      have a complex and long healing process, as they present a reduction in the angiogenic&#xD;
      response and deficiency of growth factors, making difficult the action of conventional&#xD;
      treatments. The treatment of chronic wounds is challenging, the diversity of treatments is&#xD;
      great, however the search for new modalities of effective, scientifically proven and&#xD;
      financially viable therapeutic resources that are available and readily accessible to&#xD;
      clinical practice is still desirable. Objective: To evaluate the responses of phototherapy&#xD;
      with light emitting diodes (LED) and electrical stimulation with the fixed diphasic current&#xD;
      (DF) in diabetic patient ulcers. METHODS: Diabetic volunteers of both genders, aged 30 to 65&#xD;
      years, who present chronic skin ulcers grade I or II will also be randomized (n = 13) in:&#xD;
      Treatment group with LED 620 nm (G-LED 620) , Treatment group with LED 940 nm (G-LED 940),&#xD;
      Treatment group with fixed diphasic current (G-DF) and Control group (GC). Interventions will&#xD;
      occur three times a week for 12 weeks. The evaluations will take place on the&#xD;
      pre-intervention day 1, 30, 60 and 90 days, followed by follow-up after 30 days of the end of&#xD;
      the treatment, through the following instruments: numerical scale of pain, digital&#xD;
      photography, infrared thermography, digital analgesimeter, Digital durometer, infrared&#xD;
      plethysmography and bioimpedance. Statistical analysis: To analyze the data, normality test&#xD;
      will be used to verify the distribution of the data and adequate statistical test for the&#xD;
      appropriate inter- and intragroup comparisons, being thus considered two factors in the&#xD;
      comparisons, time and group. A significance level of 5% will be adopted.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">September 1, 2017</start_date>
  <completion_date type="Anticipated">June 30, 2021</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2020</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>
    <intervention_model_description>Volunteers will also be randomized between groups:&#xD;
LED treatment group 620 nm (G-LED 620; n = 13)&#xD;
Treatment group with LED 940 nm (G-LED 940; n = 13)&#xD;
Treatment group with fixed diphasic current (G-DF; n = 13)&#xD;
Control group (G-C; n = 13)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of ulcer healing - Digital photography</measure>
    <time_frame>Twelve weeks</time_frame>
    <description>Percentage (%)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Infrared thermography</measure>
    <time_frame>Twelve weeks</time_frame>
    <description>Skin temperature (Celsius Degree)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Numerical pain scale</measure>
    <time_frame>Twelve weeks</time_frame>
    <description>Intensity of pain (numerical scale)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Von frey digital analgesiometer</measure>
    <time_frame>Twelve weeks</time_frame>
    <description>Quantify the sensitivity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Digital Durometer</measure>
    <time_frame>Twelve weeks</time_frame>
    <description>Analyze the tissue firmness (Shore)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Infrared Plethysmography</measure>
    <time_frame>Twelve weeks</time_frame>
    <description>Changes in microvascular blood volume (mL/s)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bioimpedance</measure>
    <time_frame>Twelve weeks</time_frame>
    <description>Phase angle (KHz)</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">52</enrollment>
  <condition>Ulcer</condition>
  <condition>Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>LED 620 nm group (G-LED 620)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The LED device in the red light spectrum, with a wavelength of 620 nm, will be applied over the full extent of the wound.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>LED 940 nm group (G-LED 940)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The LED device in the infrared light spectrum, with a wavelength of 940 nm, will be applied over the full extent of the wound.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fixed diphasic current group (G-DF)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The electrical stimulation will be carried out with the fixed diphasic current of the Dualpex 071 equipment, being applied throughout the extension of the wound.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group (G-C)</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Volunteers from this group will not be submitted to treatment and will only be evaluated before, every 30 days, after the 12 week period and 30 days after the last evaluation. It is worth mentioning that, after the end of its participation, if the wound is not fully healed, the treatment will be offered with LED or diphasic current.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Light emitting diodes (LED)</intervention_name>
    <description>The light-emitting diode (LED) device consists of a soft 15 x 15 cm blanket, which allows the body segment curvature of the cutaneous lesion to be monitored. The LEDs are fixed equidistant to obtain uniform irradiation over the entire ulcer. The wound site will be surrounded by a PVC film (polyvinyl chloride), to avoid contamination, for posterior positioning of the LED device, applying light directly and perpendicularly, with energy density of 6 J / cm². All LEDs will be calibrated prior to the start of applications in the Laboratory of Photobiophysics of the Faculty of Sciences and Letters of Ribeirão Preto, University of São Paulo, in which the wavelengths will be checked, the angle of radiation, power and power density.</description>
    <arm_group_label>LED 620 nm group (G-LED 620)</arm_group_label>
    <arm_group_label>LED 940 nm group (G-LED 940)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Fixed diphasic current</intervention_name>
    <description>The electrical stimulation treatment will be performed with the fixed diphasic current of the Dualpex 071 equipment (Quark®, Piracicaba, SP, Brazil), with the monopolar technique, 100 Hz, maximum intensity of 1 mA / cm² of lesion for 10 minutes. Autoclave sterilized aluminum electrodes will be used, one on the lesion (negative pole) and the other transversal to the segment (positive pole). The size of the electrode will be proportional to the extension of the lesion, having as a means of contact between the electrode and the ulcer, sterile gauze moistened with 0.9% saline solution.</description>
    <arm_group_label>Fixed diphasic current group (G-DF)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age range from 30 to 65 years;&#xD;
&#xD;
          -  Diabetic patients with neuropathic, ischemic or neuroischemic ulcers in the legs and /&#xD;
             or feet;&#xD;
&#xD;
          -  With a duration of 4 weeks or more;&#xD;
&#xD;
          -  Being grade I and / or II lesions by the Meggitt-Wagner classification;&#xD;
&#xD;
          -  Have a good degree of cognition evaluated by the Mini-Mental State Examination - MEEM&#xD;
             (Brucki et al., 2003);&#xD;
&#xD;
          -  Be under medical supervision and perform regular dressings and debridements of the&#xD;
             wound.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Those presenting with an associated disease, such as renal, neurological,&#xD;
             immunological, hematological or hepatic disease, which may interfere with evaluation&#xD;
             and / or therapeutic procedures, and which are not related to diabetes;&#xD;
&#xD;
          -  Malignancies (carcinomas);&#xD;
&#xD;
          -  Use of medications that alter the healing process (corticosteroids,&#xD;
             immunosuppressants, among others);&#xD;
&#xD;
          -  Clinical signs of infection (sepsis), acute cellulitis, osteomyelitis or gangrene;&#xD;
&#xD;
          -  Those who do not agree to sign the Free and Informed Consent Form;&#xD;
&#xD;
          -  And who do not meet the inclusion criteria described.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rinaldo Guirro, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of São Paulo</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Rinaldo Guirro, PhD</last_name>
    <phone>+551633154584</phone>
    <email>rguirro@fmrp.usp.br</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Sao Paulo</name>
      <address>
        <city>Ribeirao Preto</city>
        <state>Sao Paulo</state>
        <zip>14049-900</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 10, 2017</study_first_submitted>
  <study_first_submitted_qc>August 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <last_update_submitted>August 16, 2017</last_update_submitted>
  <last_update_submitted_qc>August 16, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Sao Paulo</investigator_affiliation>
    <investigator_full_name>Rinaldo Roberto de Jesus Guirro</investigator_full_name>
    <investigator_title>Professor, PT, PhD</investigator_title>
  </responsible_party>
  <keyword>Wound healing</keyword>
  <keyword>Phototherapy</keyword>
  <keyword>Electrotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ulcer</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/NCT03250533
org study id: U1111-1143-0079
nct id: NCT03250533
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
One of the important complications of DM is the diabetic foot that may present ulcers, which
      result from multiple risk factors, being diabetic peripheral neuropathy and ischemia due to
      peripheral vascular disease considered the main causes. In this way, the ulcers of the lower
      extremities of diabetics, have a complex and long cicatrization process. Faced with this, the
      treatment of chronic wounds is challenging, the diversity of treatments is great, however the
      search for new modalities of effective therapeutic resources, scientifically proven and
      financially feasible, that are available and easily accessible for clinical practice is still
      desirable . The aim of this study was to evaluate the responses of phototherapy with light
      emitting diodes (LED) and electrical stimulation with the fixed diphasic current (DF) in
      ulcers of diabetic patients. Diabetic volunteers who present with chronic skin ulcers will
      also be randomized (n = 13) to: Treatment group with LED 620 nm, Treatment group with LED 940
      nm, Treatment group with fixed diphasic current and Control group. Interventions will occur
      three times a week for 12 weeks and evaluations will occur on the 1st, 30th, 60th, and 90th
      day of the intervention, followed by follow-up after 30 days of treatment completion.
Background: Diabetes mellitus (DM) is a chronic disease currently considered a worldwide
      epidemic and has become a major public health problem. One of the important complications of
      DM is the diabetic foot that may present ulcers, which result from multiple risk factors,
      being diabetic peripheral neuropathy and ischemia due to peripheral vascular disease
      considered the main causes. In this way, the ulcers of the lower extremities of diabetics,
      have a complex and long healing process, as they present a reduction in the angiogenic
      response and deficiency of growth factors, making difficult the action of conventional
      treatments. The treatment of chronic wounds is challenging, the diversity of treatments is
      great, however the search for new modalities of effective, scientifically proven and
      financially viable therapeutic resources that are available and readily accessible to
      clinical practice is still desirable. Objective: To evaluate the responses of phototherapy
      with light emitting diodes (LED) and electrical stimulation with the fixed diphasic current
      (DF) in diabetic patient ulcers. METHODS: Diabetic volunteers of both genders, aged 30 to 65
      years, who present chronic skin ulcers grade I or II will also be randomized (n = 13) in:
      Treatment group with LED 620 nm (G-LED 620) , Treatment group with LED 940 nm (G-LED 940),
      Treatment group with fixed diphasic current (G-DF) and Control group (GC). Interventions will
      occur three times a week for 12 weeks. The evaluations will take place on the
      pre-intervention day 1, 30, 60 and 90 days, followed by follow-up after 30 days of the end of
      the treatment, through the following instruments: numerical scale of pain, digital
      photography, infrared thermography, digital analgesimeter, Digital durometer, infrared
      plethysmography and bioimpedance. Statistical analysis: To analyze the data, normality test
      will be used to verify the distribution of the data and adequate statistical test for the
      appropriate inter- and intragroup comparisons, being thus considered two factors in the
      comparisons, time and group. A significance level of 5% will be adopted.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Volunteers will also be randomized between groups:
LED treatment group 620 nm (G-LED 620; n = 13)
Treatment group with LED 940 nm (G-LED 940; n = 13)
Treatment group with fixed diphasic current (G-DF; n = 13)
Control group (G-C; n = 13)
primary purpose: Treatment
masking: Double (Investigator, Outcomes Assessor)
measure: Rate of ulcer healing - Digital photography
time frame: Twelve weeks
description: Percentage (%)
measure: Infrared thermography
time frame: Twelve weeks
description: Skin temperature (Celsius Degree)
measure: Numerical pain scale
time frame: Twelve weeks
description: Intensity of pain (numerical scale)
measure: Von frey digital analgesiometer
time frame: Twelve weeks
description: Quantify the sensitivity
measure: Digital Durometer
time frame: Twelve weeks
description: Analyze the tissue firmness (Shore)
measure: Infrared Plethysmography
time frame: Twelve weeks
description: Changes in microvascular blood volume (mL/s)
measure: Bioimpedance
time frame: Twelve weeks
description: Phase angle (KHz)
arm group label: LED 620 nm group (G-LED 620)
arm group type: Experimental
description: The LED device in the red light spectrum, with a wavelength of 620 nm, will be applied over the full extent of the wound.
arm group label: LED 940 nm group (G-LED 940)
arm group type: Experimental
description: The LED device in the infrared light spectrum, with a wavelength of 940 nm, will be applied over the full extent of the wound.
arm group label: Fixed diphasic current group (G-DF)
arm group type: Experimental
description: The electrical stimulation will be carried out with the fixed diphasic current of the Dualpex 071 equipment, being applied throughout the extension of the wound.
arm group label: Control group (G-C)
arm group type: No Intervention
description: Volunteers from this group will not be submitted to treatment and will only be evaluated before, every 30 days, after the 12 week period and 30 days after the last evaluation. It is worth mentioning that, after the end of its participation, if the wound is not fully healed, the treatment will be offered with LED or diphasic current.
intervention type: Device
intervention name: Light emitting diodes (LED)
description: The light-emitting diode (LED) device consists of a soft 15 x 15 cm blanket, which allows the body segment curvature of the cutaneous lesion to be monitored. The LEDs are fixed equidistant to obtain uniform irradiation over the entire ulcer. The wound site will be surrounded by a PVC film (polyvinyl chloride), to avoid contamination, for posterior positioning of the LED device, applying light directly and perpendicularly, with energy density of 6 J / cm². All LEDs will be calibrated prior to the start of applications in the Laboratory of Photobiophysics of the Faculty of Sciences and Letters of Ribeirão Preto, University of São Paulo, in which the wavelengths will be checked, the angle of radiation, power and power density.
arm group label: LED 620 nm group (G-LED 620)
arm group label: LED 940 nm group (G-LED 940)
intervention type: Device
intervention name: Fixed diphasic current
description: The electrical stimulation treatment will be performed with the fixed diphasic current of the Dualpex 071 equipment (Quark®, Piracicaba, SP, Brazil), with the monopolar technique, 100 Hz, maximum intensity of 1 mA / cm² of lesion for 10 minutes. Autoclave sterilized aluminum electrodes will be used, one on the lesion (negative pole) and the other transversal to the segment (positive pole). The size of the electrode will be proportional to the extension of the lesion, having as a means of contact between the electrode and the ulcer, sterile gauze moistened with 0.9% saline solution.
arm group label: Fixed diphasic current group (G-DF)
criteria: 
gender: All
minimum age: 30 Years
maximum age: 65 Years
healthy volunteers: No
last name: Rinaldo Guirro, PhD
role: Principal Investigator
affiliation: University of São Paulo
last name: Rinaldo Guirro, PhD
phone: +551633154584
email: rguirro@fmrp.usp.br
facility: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: University of Sao Paulo
investigator full name: Rinaldo Roberto de Jesus Guirro
investigator title: Professor, PT, PhD
mesh term: Ulcer