<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/NCT03270293</url>
  </required_header>
  <id_info>
    <org_study_id>E1214</org_study_id>
    <nct_id>NCT03270293</nct_id>
  </id_info>
  <brief_title>Efficacy and Tolerance Evaluation of a Bio-revitalizing Product Containing Hyaluronic Acid With High and Low Molecular Weight</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>Derming SRL</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Derming SRL</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary end point of the study was to evaluate clinically and by non-invasive instrumental&#xD;
      evaluations tolerance and efficacy of a bio-revitalizing product containing hyaluronic acid&#xD;
      with high (H-HA) and low (L-HA) molecular weight; the micro-injection of the study product&#xD;
      was performed by a specialized dermatologist, bilaterally on the face (zygomatic&#xD;
      protuberance, nostril's angle, inferior margin of tragus, lip marionette lines, mandibular&#xD;
      angle) of healthy female volunteers aged 30-60 years.&#xD;
&#xD;
      It was also aim of this study to evaluate efficacy by the volunteers and tolerance both by&#xD;
      investigator and volunteers.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>March 2015</start_date>
  <completion_date type="Actual">August 2015</completion_date>
  <primary_completion_date type="Actual">July 2015</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Wrinkle Severity Rating Scale (WSRS) improvement</measure>
    <time_frame>Basal visit (T0), Week 4 (T4W) , Week 8 (T8W), Week 12 (T12W), Week 16 (T16W).</time_frame>
    <description>Reduction of wrinkles severity corresponding to a decrease from the baseline of the Wrinkle Severity Rating Scale (WSRS) clinical score where:&#xD;
Grade 1 (absent): no visible nasolabial fold; continuous skin line. Grade 2 (mild): shallow but visible nasolabial fold with a slight indentation; minor facial feature.&#xD;
Grade 3 (moderate): moderately deep nasolabial folds; clear facial feature visible at normal appearance but not when stretched.&#xD;
Grade 4 (severe): very long and deep nasolabial folds; prominent facial feature; &lt;2mm visible fold when stretched.&#xD;
Grade 5 (very severe): extremely deep and long nasolabial fold, detrimental to facial appearance; 2-4 mm visible V-shaped fold when stretched.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Facial Volume Loss Scale (FVLS) improvement</measure>
    <time_frame>16 weeks</time_frame>
    <description>Reduction of face volume loss corresponding to a decrease from the baseline of the Facial Volume Loss Scale (FVLS) where Grade 1 Mild flattening or shadowing of one or more facial regions (including the cheek, temple, preauricolar and periorbital areas). No prominent bony landmarks. No visibility of underlying musculature.&#xD;
Grade 2 An intermediate point between grade 1 and grade 3. Grade 3 Moderate concavity of one or more facial regions (including the cheek, temple, preauricolar and periorbital areas. Prominence of bony landmarks. May have visibility of underlying musculature.&#xD;
Grade 4 An intermediate point between grade 3 and grade 5. Grade 5 Severe indentation of one or more facial regions (including the cheek, temple, preauricolar and periorbital areas). Severe prominence of bony landmarks. Clear visibility of underlying musculature.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Surface microrelief's regularity improvement</measure>
    <time_frame>Basal visit (T0), Week 4 (T4W) , Week 8 (T8W), Week 12 (T12W), Week 16 (T16W).</time_frame>
    <description>Improvement of skin surface microrelief corresponding to a reduction of the clinical score of microrelief's regularity grade where Grade 1:very regular, Grade 2: regular, Grade 3: irregular, Grade 4: very irregular.&#xD;
Clinical evaluation of surface microrelief's regularity grade is carried out on the digital picture acquired by FotoFinderDermoscope with a magnification of 20X</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Determination of profilometric parameters</measure>
    <time_frame>Basal visit (T0), Week 4 (T4W) , Week 8 (T8W), Week 12 (T12W), Week 16 (T16W).</time_frame>
    <description>Reduction of the nasolabial fold and marionette lines profilometric parameters versus baseline where Ra is average roughness of the analysed profile, Rt is wrinkles total high, Rv is wrinkles maximum depth.&#xD;
Replicas of nasolabial fold and marionette lines are obtained using silicone rubber. A picture of the skin replicas is taken thanks to Primos compact portable device (GFMesstechnik); Primos software is able to elaborate 3D representations of skin wrinkles as well as to measure skin principal profilometric parameters.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Skin plastoelasticity improvement</measure>
    <time_frame>Basal visit (T0), Week 4 (T4W) , Week 8 (T8W), Week 12 (T12W), Week 16 (T16W).</time_frame>
    <description>Improvement of the principal torsiometric parameters Ue (immediate extensibility), Uf (final extensibility), Uv (viscoelasticity) and Ur (immediate elastic recovery).Skin firmness is measured with the instrument Dermal Torque Meter (Dia-Stron Ltd., UK).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Superficial skin hydration improvement</measure>
    <time_frame>Basal visit (T0), Week 4 (T4W) , Week 8 (T8W), Week 12 (T12W), Week 16 (T16W).</time_frame>
    <description>Improvement of skin electrical capacitance value measured with Corneometer CM825 (Courage - Khazaka, Köln, Germany).&#xD;
The measure of the skin capacitance properties is an indirect expression of its hydration level.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Deep skin hydration improvement</measure>
    <time_frame>Basal visit (T0), Week 4 (T4W) , Week 8 (T8W), Week 12 (T12W), Week 16 (T16W).</time_frame>
    <description>Improvement of tissue dielectric constant value of superficial and deep skin layers measured with MoistureMeterD (Delfin Technologies, Kuopio - Finland)</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">64</enrollment>
  <condition>Malar and Sub-malar Volume Deficiency</condition>
  <arm_group>
    <arm_group_label>Profhilo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The intradermal procedure was performed bilaterally on the face, at level of the following five points:&#xD;
zygomatic protuberance&#xD;
nostril's angle&#xD;
inferior margin of tragus&#xD;
lip marionette lines&#xD;
mandibular angle. The amount of product injected, was 0.2 ml for each injection-point.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Profhilo</intervention_name>
    <arm_group_label>Profhilo</arm_group_label>
    <other_name>IBSA</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  female sex&#xD;
&#xD;
          -  age 30-60 years&#xD;
&#xD;
          -  agreeing to present at each study visit without make-up&#xD;
&#xD;
          -  accepting to not change their habits regarding food, physical activity, make-up use,&#xD;
             face cosmetic and cleansing products&#xD;
&#xD;
          -  accepting not to expose their face to strong UV irradiation (UV session, or sun&#xD;
             bathes), during the entire duration of the study, without appropriate sun protection&#xD;
&#xD;
          -  accepting to sign the Informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  lactation&#xD;
&#xD;
          -  subjects not in menopause who do not use adequate contraceptive precautions in order&#xD;
             to avoid pregnancies during the study&#xD;
&#xD;
          -  subjects not in menopause who do not accept to perform the pregnancy test during the&#xD;
             basal visit, 4 and 8 weeks after the first biomineralising treatment execution&#xD;
&#xD;
          -  performing skin treatments for aesthetic correction (biomaterials implants, face&#xD;
             lifting, botox injections, laser, chemical peeling) in the 12 months prior to the&#xD;
             study start&#xD;
&#xD;
          -  performing permanent filler in the past&#xD;
&#xD;
          -  change in the normal habits regarding food, physical activity, face cosmetic,&#xD;
             cleansing and make-up use during the month preceding the test&#xD;
&#xD;
          -  sensitivity to the test product or its ingredients (an accurate anamnestic assessment&#xD;
             will performed by the investigator)&#xD;
&#xD;
          -  subjects whose insufficient adhesion to the study protocol is foreseeable&#xD;
&#xD;
          -  participation in a similar study actually or during the previous 3 months.&#xD;
&#xD;
          -  presence of cutaneous disease on the tested area, as lesions, scars, malformations&#xD;
&#xD;
          -  recurrent facial/labial herpes&#xD;
&#xD;
          -  clinical and significant skin condition on the test area (e.g. active eczema,&#xD;
             dermatitis, psoriasis etc.).&#xD;
&#xD;
          -  diabetes&#xD;
&#xD;
          -  endocrine disease&#xD;
&#xD;
          -  hepatic disorder&#xD;
&#xD;
          -  renal disorder&#xD;
&#xD;
          -  cardiac disorder&#xD;
&#xD;
          -  pulmonary disease&#xD;
&#xD;
          -  cancer&#xD;
&#xD;
          -  neurological or psychological disease&#xD;
&#xD;
          -  inflammatory/immunosuppressive disease&#xD;
&#xD;
          -  drug allergy.&#xD;
&#xD;
          -  anti-inflammatory drugs, anti-histaminic, topic and systemic corticosteroids,&#xD;
             narcotic, antidepressant, immunosuppressive drugs (with the except of contraceptive or&#xD;
             hormonal treatment starting more than 1 year ago)&#xD;
&#xD;
          -  assumption of drugs able to influence the test results in the investigator opinion.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Adele Sparavigna, Doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Derming SRL</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>DERMING</name>
      <address>
        <city>Monza</city>
        <state>Monza-brianza</state>
        <zip>20900</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>January 2016</verification_date>
  <study_first_submitted>January 15, 2016</study_first_submitted>
  <study_first_submitted_qc>August 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 1, 2017</study_first_posted>
  <last_update_submitted>September 1, 2017</last_update_submitted>
  <last_update_submitted_qc>September 1, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 5, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Derming SRL</investigator_affiliation>
    <investigator_full_name>Adele Sparavigna</investigator_full_name>
    <investigator_title>Medical Doctor</investigator_title>
  </responsible_party>
  <!-- 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/NCT03270293
org study id: E1214
nct id: NCT03270293
lead sponsor: 
has dmc: No
Primary end point of the study was to evaluate clinically and by non-invasive instrumental
      evaluations tolerance and efficacy of a bio-revitalizing product containing hyaluronic acid
      with high (H-HA) and low (L-HA) molecular weight; the micro-injection of the study product
      was performed by a specialized dermatologist, bilaterally on the face (zygomatic
      protuberance, nostril's angle, inferior margin of tragus, lip marionette lines, mandibular
      angle) of healthy female volunteers aged 30-60 years.

      It was also aim of this study to evaluate efficacy by the volunteers and tolerance both by
      investigator and volunteers.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Wrinkle Severity Rating Scale (WSRS) improvement
time frame: Basal visit (T0), Week 4 (T4W) , Week 8 (T8W), Week 12 (T12W), Week 16 (T16W).
description: Reduction of wrinkles severity corresponding to a decrease from the baseline of the Wrinkle Severity Rating Scale (WSRS) clinical score where:
Grade 1 (absent): no visible nasolabial fold; continuous skin line. Grade 2 (mild): shallow but visible nasolabial fold with a slight indentation; minor facial feature.
Grade 3 (moderate): moderately deep nasolabial folds; clear facial feature visible at normal appearance but not when stretched.
Grade 4 (severe): very long and deep nasolabial folds; prominent facial feature; <2mm visible fold when stretched.
Grade 5 (very severe): extremely deep and long nasolabial fold, detrimental to facial appearance; 2-4 mm visible V-shaped fold when stretched.
measure: Facial Volume Loss Scale (FVLS) improvement
time frame: 16 weeks
description: Reduction of face volume loss corresponding to a decrease from the baseline of the Facial Volume Loss Scale (FVLS) where Grade 1 Mild flattening or shadowing of one or more facial regions (including the cheek, temple, preauricolar and periorbital areas). No prominent bony landmarks. No visibility of underlying musculature.
Grade 2 An intermediate point between grade 1 and grade 3. Grade 3 Moderate concavity of one or more facial regions (including the cheek, temple, preauricolar and periorbital areas. Prominence of bony landmarks. May have visibility of underlying musculature.
Grade 4 An intermediate point between grade 3 and grade 5. Grade 5 Severe indentation of one or more facial regions (including the cheek, temple, preauricolar and periorbital areas). Severe prominence of bony landmarks. Clear visibility of underlying musculature.
measure: Surface microrelief's regularity improvement
time frame: Basal visit (T0), Week 4 (T4W) , Week 8 (T8W), Week 12 (T12W), Week 16 (T16W).
description: Improvement of skin surface microrelief corresponding to a reduction of the clinical score of microrelief's regularity grade where Grade 1:very regular, Grade 2: regular, Grade 3: irregular, Grade 4: very irregular.
Clinical evaluation of surface microrelief's regularity grade is carried out on the digital picture acquired by FotoFinderDermoscope with a magnification of 20X
measure: Determination of profilometric parameters
time frame: Basal visit (T0), Week 4 (T4W) , Week 8 (T8W), Week 12 (T12W), Week 16 (T16W).
description: Reduction of the nasolabial fold and marionette lines profilometric parameters versus baseline where Ra is average roughness of the analysed profile, Rt is wrinkles total high, Rv is wrinkles maximum depth.
Replicas of nasolabial fold and marionette lines are obtained using silicone rubber. A picture of the skin replicas is taken thanks to Primos compact portable device (GFMesstechnik); Primos software is able to elaborate 3D representations of skin wrinkles as well as to measure skin principal profilometric parameters.
measure: Skin plastoelasticity improvement
time frame: Basal visit (T0), Week 4 (T4W) , Week 8 (T8W), Week 12 (T12W), Week 16 (T16W).
description: Improvement of the principal torsiometric parameters Ue (immediate extensibility), Uf (final extensibility), Uv (viscoelasticity) and Ur (immediate elastic recovery).Skin firmness is measured with the instrument Dermal Torque Meter (Dia-Stron Ltd., UK).
measure: Superficial skin hydration improvement
time frame: Basal visit (T0), Week 4 (T4W) , Week 8 (T8W), Week 12 (T12W), Week 16 (T16W).
description: Improvement of skin electrical capacitance value measured with Corneometer CM825 (Courage - Khazaka, Köln, Germany).
The measure of the skin capacitance properties is an indirect expression of its hydration level.
measure: Deep skin hydration improvement
time frame: Basal visit (T0), Week 4 (T4W) , Week 8 (T8W), Week 12 (T12W), Week 16 (T16W).
description: Improvement of tissue dielectric constant value of superficial and deep skin layers measured with MoistureMeterD (Delfin Technologies, Kuopio - Finland)
arm group label: Profhilo
arm group type: Experimental
description: The intradermal procedure was performed bilaterally on the face, at level of the following five points:
zygomatic protuberance
nostril's angle
inferior margin of tragus
lip marionette lines
mandibular angle. The amount of product injected, was 0.2 ml for each injection-point.
intervention type: Device
intervention name: Profhilo
arm group label: Profhilo
other name: IBSA
criteria: 
gender: Female
minimum age: 30 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Adele Sparavigna, Doctor
role: Principal Investigator
affiliation: Derming SRL
facility: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: Derming SRL
investigator full name: Adele Sparavigna
investigator title: Medical Doctor