<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/NCT03754205</url>
  </required_header>
  <id_info>
    <org_study_id>674/03-09-2018</org_study_id>
    <nct_id>NCT03754205</nct_id>
  </id_info>
  <brief_title>Vaginal CO2 Laser and the Genitourinary Syndrome of Menopause</brief_title>
  <official_title>The Clinical, Histopathological, Cytological and Microbiological Efficacy of the Micro-ablative Fractional CO2 Laser : A Double-blind Randomized Placebo-controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National and Kapodistrian University of Athens</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>IRCCS San Raffaele</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>National and Kapodistrian University of Athens</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>
      This study evaluates the clinical, histopathological, cytological and microbiological&#xD;
      efficacy of Microablative Fractional CO2 laser intravaginally administered in postmenopausal&#xD;
      women with Genitourinary Syndrome of Menopause. Half participants will receive active CO2&#xD;
      laser therapy, while the other half will receive placebo CO2 laser therapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">January 18, 2018</start_date>
  <completion_date type="Anticipated">January 15, 2021</completion_date>
  <primary_completion_date type="Anticipated">April 15, 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>10-centimeter Visual Analogue Scale assessing intensity of dyspareunia and dryness</measure>
    <time_frame>24-months</time_frame>
    <description>It is a straight line with 2 endpoints &quot;0&quot; and &quot;10&quot;. Zero defines &quot;no dyspareunia at all&quot; and &quot;no dryness at all&quot; , while 10 &quot;dyspareunia as bad as it could be&quot; and &quot;dryness as bad as it could be&quot;. Participants will draw a line at or between the 2 end points. The distance between zero and drawn line will define the intensity of dyspareunia and dryness</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Day-to Day Impact of vaginal aging questionnaire (DIVA)</measure>
    <time_frame>24 months</time_frame>
    <description>It includes 4 domains: activities of daily living (5 items), sexual functioning (5 items), emotional well-being (4 items), self-concept and body image (5-items). Each item of each domain could receive values from 0 to 4. Mean scores are calculated on each of the domain scales. Higher scores indicate greater symptom impact</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients Global Impression of Improvement</measure>
    <time_frame>24 months</time_frame>
    <description>It is a single question with 7 possible answers. Patients will chose the answer that applies at their impression of improvement after the laser therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>10-centimeter Visual Analogue Scale assessing intensity of itching, burning and dysuria</measure>
    <time_frame>24 months</time_frame>
    <description>It is a straight line with 2 endpoints &quot;0&quot; and &quot;10&quot;. Zero defines &quot;no symptom at all&quot;, while 10 &quot;symptom as bad as it could be&quot; and &quot;dryness as bad as it could be&quot;. Participants will draw a line at or between the 2 end points. The distance between zero and drawn line will define the intensity of symptom</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>3 days voiding diary</measure>
    <time_frame>24 months</time_frame>
    <description>Assesses bladder function (frequency, urgency and incontinence)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Female Sexual Function Index</measure>
    <time_frame>24 months</time_frame>
    <description>It includes 6 domains assessing sexual functioning (desire, arousal, orgasm, lubrication, satisfaction and pain). Total score is calculated by summing scores of the 5 domains multiplied by certain factors with a minimum value of 2 and maximum 36</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>International Consultation on Incontinence Questionnaire Short Form/Female Lower Urinary tract Symptoms (ICIQ-FLUTS)</measure>
    <time_frame>24 months</time_frame>
    <description>It is a 12-items questionnaire evaluating nocturia, urgency, bladder pain, frequency, hesitancy, straining, intermittency, urinary incontinence (urge, stress and unexplained), frequency of urinary incontinence and nocturnal enuresis. Filling, voiding and incontinence symptoms subscales range from 0 to 15, 0 to 12 and 0 to 20, respectively.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>King's Health Questionnaire (KHQ)</measure>
    <time_frame>24 months</time_frame>
    <description>It has 3 sections: 1) general health and overall health related to urinary symptoms with 2 questions, 2) incontinence impact, role limitations, physical limitations, social limitations, personal limitations, emotions, sleep and energy, and severity coping measures with 19 questions and 3) bother or impact of urinary symptoms with 11 questions. Scores of each domain of the 2 sections range from 0 to 100. Scores of the third section range from 0 to 3. Higher scores indicate higher impact of urinary incontinence.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vaginal Maturation Value</measure>
    <time_frame>24 months</time_frame>
    <description>It is calculated by defining the percentage of superficial, intermediate and parabasal epithelial cells on the vaginal pap smear, following the formula (1x%superficial)+(0.5x%intermediate)+(0x%parabasal). It may receive values from 0 to 100%.It is considered to be an indicator of the estrogenic stimulation, whereas values of 0-49%, 50-64% and 65-100% indicate absent/low, moderate and high estrogenic effect on the vaginal epithelium, respectively.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vaginal Health Index Score</measure>
    <time_frame>24 months</time_frame>
    <description>It evaluates vaginal elasticity, fluid volume, ph of vaginal fluid, epithelial integrity and moisture. Each one of these may receive scores from 1 to 5. Total score is calculated by summing the 5 scores ranging from 5 to 25. Higher scores indicate better vaginal status.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Epithelial thickness</measure>
    <time_frame>24 months</time_frame>
    <description>Biopsies will be obtained from the lateral vaginal wall. Epithelial thickness (in μ) will be measured by a vertical line between basal layer cells and superficial layers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Blood vessels</measure>
    <time_frame>24 months</time_frame>
    <description>Computerized determination of number of capillary profiles in the test area will be performed percent of total area of subepithelial stroma), will be performed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Size of blood vessels</measure>
    <time_frame>24 months</time_frame>
    <description>Computerized determination of diameter (in μ), length (in μ) αnd width (in μ) will be performed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Density of blood vessels</measure>
    <time_frame>24 months</time_frame>
    <description>Computerized determination of volume density of blood vessels in percent of total area of subepithelial stroma will be performed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cultures of vaginal samples</measure>
    <time_frame>24 months</time_frame>
    <description>Lactobacilli, aerobic bacteria, anaerobic bacteria, fungi will be evaluated</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Polymerase Chain Reaction</measure>
    <time_frame>24 months</time_frame>
    <description>Lactobacilli, bacteria and fungi will be evaluated.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Vaginal Atrophy</condition>
  <arm_group>
    <arm_group_label>Laser Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Microablative Fractional CO2 laser therapy at monthly intervals.&#xD;
The laser parameters that will be used are the following: (1) Power: 30 ή 40 watts, 2) Dwell time:1000μs, 3) Spacing 1000 μm, 4) Depth: SmartStak parameter from 1-3 depending on the treatment status, 5) D-pulse mode.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo CO2 laser therapies at monthly intervals.&#xD;
The laser parameters that will be used are the following: 1) Power: 0.5 watts, 2) Dwell time:1000μs, 3) Spacing 1000 μm, 4) Depth: SmartStak parameter 1, 5) Smart-pulse mode.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Microablative Fractional CO2 laser</intervention_name>
    <description>3 therapies intravaginally administered will be applied at monthly intervals</description>
    <arm_group_label>Laser Group</arm_group_label>
    <arm_group_label>Placebo Group</arm_group_label>
    <other_name>SmartXide2 V2LR, Monalisa Touch, DEKA, Florence, Italy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Symptoms of vaginal atrophy (dyspareunia and/or vaginal dryness)&#xD;
&#xD;
          -  Menopause&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Systemic or local hormonal therapy the last 6 months&#xD;
&#xD;
          -  Use of moisturizers or lubricants the last month&#xD;
&#xD;
          -  Active genital infection (i.e herpes, vaginitis)&#xD;
&#xD;
          -  Prolapse stage &gt;=2&#xD;
&#xD;
          -  Underlying pathologies that could interfere with the protocol compliance&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Female</gender_description>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stavros Athanasiou, Associate Proffesor</last_name>
    <role>Principal Investigator</role>
    <affiliation>National and Kapodistrian University of Athens, Greece</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Urogynecological Unit of Alexandra Hospital</name>
      <address>
        <city>Athens</city>
        <zip>11528</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Greece</country>
  </location_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>October 28, 2018</study_first_submitted>
  <study_first_submitted_qc>November 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 27, 2018</study_first_posted>
  <last_update_submitted>January 13, 2020</last_update_submitted>
  <last_update_submitted_qc>January 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National and Kapodistrian University of Athens</investigator_affiliation>
    <investigator_full_name>Themos Grigoriadis</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrophy</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/NCT03754205
org study id: 674/03-09-2018
nct id: NCT03754205
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study evaluates the clinical, histopathological, cytological and microbiological
      efficacy of Microablative Fractional CO2 laser intravaginally administered in postmenopausal
      women with Genitourinary Syndrome of Menopause. Half participants will receive active CO2
      laser therapy, while the other half will receive placebo CO2 laser therapy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: 10-centimeter Visual Analogue Scale assessing intensity of dyspareunia and dryness
time frame: 24-months
description: It is a straight line with 2 endpoints "0" and "10". Zero defines "no dyspareunia at all" and "no dryness at all" , while 10 "dyspareunia as bad as it could be" and "dryness as bad as it could be". Participants will draw a line at or between the 2 end points. The distance between zero and drawn line will define the intensity of dyspareunia and dryness
measure: Day-to Day Impact of vaginal aging questionnaire (DIVA)
time frame: 24 months
description: It includes 4 domains: activities of daily living (5 items), sexual functioning (5 items), emotional well-being (4 items), self-concept and body image (5-items). Each item of each domain could receive values from 0 to 4. Mean scores are calculated on each of the domain scales. Higher scores indicate greater symptom impact
measure: Patients Global Impression of Improvement
time frame: 24 months
description: It is a single question with 7 possible answers. Patients will chose the answer that applies at their impression of improvement after the laser therapy
measure: 10-centimeter Visual Analogue Scale assessing intensity of itching, burning and dysuria
time frame: 24 months
description: It is a straight line with 2 endpoints "0" and "10". Zero defines "no symptom at all", while 10 "symptom as bad as it could be" and "dryness as bad as it could be". Participants will draw a line at or between the 2 end points. The distance between zero and drawn line will define the intensity of symptom
measure: 3 days voiding diary
time frame: 24 months
description: Assesses bladder function (frequency, urgency and incontinence)
measure: Female Sexual Function Index
time frame: 24 months
description: It includes 6 domains assessing sexual functioning (desire, arousal, orgasm, lubrication, satisfaction and pain). Total score is calculated by summing scores of the 5 domains multiplied by certain factors with a minimum value of 2 and maximum 36
measure: International Consultation on Incontinence Questionnaire Short Form/Female Lower Urinary tract Symptoms (ICIQ-FLUTS)
time frame: 24 months
description: It is a 12-items questionnaire evaluating nocturia, urgency, bladder pain, frequency, hesitancy, straining, intermittency, urinary incontinence (urge, stress and unexplained), frequency of urinary incontinence and nocturnal enuresis. Filling, voiding and incontinence symptoms subscales range from 0 to 15, 0 to 12 and 0 to 20, respectively.
measure: King's Health Questionnaire (KHQ)
time frame: 24 months
description: It has 3 sections: 1) general health and overall health related to urinary symptoms with 2 questions, 2) incontinence impact, role limitations, physical limitations, social limitations, personal limitations, emotions, sleep and energy, and severity coping measures with 19 questions and 3) bother or impact of urinary symptoms with 11 questions. Scores of each domain of the 2 sections range from 0 to 100. Scores of the third section range from 0 to 3. Higher scores indicate higher impact of urinary incontinence.
measure: Vaginal Maturation Value
time frame: 24 months
description: It is calculated by defining the percentage of superficial, intermediate and parabasal epithelial cells on the vaginal pap smear, following the formula (1x%superficial)+(0.5x%intermediate)+(0x%parabasal). It may receive values from 0 to 100%.It is considered to be an indicator of the estrogenic stimulation, whereas values of 0-49%, 50-64% and 65-100% indicate absent/low, moderate and high estrogenic effect on the vaginal epithelium, respectively.
measure: Vaginal Health Index Score
time frame: 24 months
description: It evaluates vaginal elasticity, fluid volume, ph of vaginal fluid, epithelial integrity and moisture. Each one of these may receive scores from 1 to 5. Total score is calculated by summing the 5 scores ranging from 5 to 25. Higher scores indicate better vaginal status.
measure: Epithelial thickness
time frame: 24 months
description: Biopsies will be obtained from the lateral vaginal wall. Epithelial thickness (in μ) will be measured by a vertical line between basal layer cells and superficial layers.
measure: Number of Blood vessels
time frame: 24 months
description: Computerized determination of number of capillary profiles in the test area will be performed percent of total area of subepithelial stroma), will be performed.
measure: Size of blood vessels
time frame: 24 months
description: Computerized determination of diameter (in μ), length (in μ) αnd width (in μ) will be performed.
measure: Density of blood vessels
time frame: 24 months
description: Computerized determination of volume density of blood vessels in percent of total area of subepithelial stroma will be performed
measure: Cultures of vaginal samples
time frame: 24 months
description: Lactobacilli, aerobic bacteria, anaerobic bacteria, fungi will be evaluated
measure: Polymerase Chain Reaction
time frame: 24 months
description: Lactobacilli, bacteria and fungi will be evaluated.
arm group label: Laser Group
arm group type: Experimental
description: Microablative Fractional CO2 laser therapy at monthly intervals.
The laser parameters that will be used are the following: (1) Power: 30 ή 40 watts, 2) Dwell time:1000μs, 3) Spacing 1000 μm, 4) Depth: SmartStak parameter from 1-3 depending on the treatment status, 5) D-pulse mode.
arm group label: Placebo Group
arm group type: Placebo Comparator
description: Placebo CO2 laser therapies at monthly intervals.
The laser parameters that will be used are the following: 1) Power: 0.5 watts, 2) Dwell time:1000μs, 3) Spacing 1000 μm, 4) Depth: SmartStak parameter 1, 5) Smart-pulse mode.
intervention type: Device
intervention name: Microablative Fractional CO2 laser
description: 3 therapies intravaginally administered will be applied at monthly intervals
arm group label: Laser Group
arm group label: Placebo Group
other name: SmartXide2 V2LR, Monalisa Touch, DEKA, Florence, Italy
criteria: 
gender: Female
gender based: Yes
gender description: Female
minimum age: N/A
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Stavros Athanasiou, Associate Proffesor
role: Principal Investigator
affiliation: National and Kapodistrian University of Athens, Greece
facility: 
country: Greece
responsible party type: Principal Investigator
investigator affiliation: National and Kapodistrian University of Athens
investigator full name: Themos Grigoriadis
investigator title: Assistant Professor
mesh term: Atrophy