<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/NCT01695707</url>
  </required_header>
  <id_info>
    <org_study_id>RSRB00041078</org_study_id>
    <secondary_id>1R21AR062357</secondary_id>
    <nct_id>NCT01695707</nct_id>
  </id_info>
  <brief_title>Assessing the Impact of Pioglitazone on Skin Barrier Function in Atopic Dermatitis Patients</brief_title>
  <official_title>Assessing the Impact of Pioglitazone on Skin Barrier Function in Atopic Dermatitis Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Rochester</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Rochester</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Many patients with eczema (atopic dermatitis) have an inherent defect in their skin barrier&#xD;
      as demonstrated by high water loss. In laboratory conditions, studies have shown that&#xD;
      pioglitazone restores the skin barrier function in skin from eczema patients. The purpose of&#xD;
      this study is to determine if taking pioglitazone improves the skin barrier function in&#xD;
      people with eczema.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Enrolled patients will be randomized to either placebo or pioglitazone. Each randomized&#xD;
      subject will have a skin biopsy and skin irritancy assay performed prior to treatment and at&#xD;
      the end of 12 weeks of treatment. Noninvasive barrier measurements including transepidermal&#xD;
      water loss will be recorded at all study visits.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Insufficient Funding.&#xD;
  </why_stopped>
  <start_date>March 2013</start_date>
  <completion_date type="Anticipated">June 2014</completion_date>
  <primary_completion_date type="Anticipated">January 2014</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>Noninvasive barrier measurements (TEWL)</measure>
    <description>Transepidermal Water Loss (TEWL) will be measured at multiple time points throughout the study as a surrogate for skin barrier integrity.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Transepithelial electrical resistance (TEER) and permeability</measure>
    <description>Skin biopsies will be performed twice during the study. The integrity of the skin barrier will be assessed in the lab by transepithelial electrical resistance (TEER) and permeability of the biopsy specimens.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>mRNA</measure>
    <description>Ex vivo assessment of mRNA expression of key epidermal barrier proteins will also be performed on the biopsy specimens.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Skin Irritancy</measure>
    <description>The clinical efficacy of PIO will be assessed by quantifying the skin response to a model irritant, sodium lauryl sulphate (SLS) at several time points. Subjects will be exposed for 24 h on the dominant inner arm to SLS at three concentrations (wt/vol in water - 0.125, 0.5 and 2%) (Fluka) using standard patch test reagents (Finn chambers of 18-mm diam, Filter Discs &amp; Scanpor tape). Before application and at several time points after removal, TEWL and erythema will be measured at the exposed site and at a control site. Erythema will be measured using a colorimeter (Minolta CR-200).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Atopic Dermatitis</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects randomized to placebo will receive opaque size &quot;00&quot; gelatin capsules containing 240mg lactose. As with the intervention group, 1 capsule will be taken by each day throughout the treatment period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pioglitazone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects randomized to pioglitazone will receive opaque size &quot;00&quot; gelatin capsules containing pioglitazone. For the first 3 weeks, capsules will contain 30 mg pioglitazone. For the remaining 9 weeks of the treatment period, capsules will contain 45 mg pioglitazone unless subjects are unable to tolerate this increased dose.&#xD;
One capsule will be taken by each day throughout the treatment period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pioglitazone</intervention_name>
    <description>see Arm Description</description>
    <arm_group_label>Pioglitazone</arm_group_label>
    <other_name>Actos</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo (for pioglitazone)</intervention_name>
    <description>see Arm Description</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  i. Moderate to Severe AD: EASI ≥ 10 ii. Active Atopic Dermatitis: Subjects must have&#xD;
             within the last 3 months according to medical records or by medical exam of the&#xD;
             investigator:&#xD;
&#xD;
               -  Pruritus&#xD;
&#xD;
               -  Eczema (acute, subacute, chronic)&#xD;
&#xD;
        I. Typical morphology and age-specific patterns - Patterns include (1) facial, neck, and&#xD;
        extensor involvement in infants and children, (2) current or prior flexural lesions in any&#xD;
        age group, (3) sparing groin and axillary regions.&#xD;
&#xD;
        II. Chronic or relapsing history&#xD;
&#xD;
        iii. Extrinsic they must also meet both of the following: serum total IgE ≥ 1.5 S.D.&#xD;
        greater than the age-matched norms and positive multi-allergen RAST (Phadiatop).&#xD;
&#xD;
        Additionally, subjects must have TEWL of nonlesional skin of upper arm that is ≥ 8 gm/m2/h&#xD;
        at screening visit. This is to ensure that we are in fact studying the subset of AD&#xD;
        subjects who have a skin barrier defect.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unwillingness or inability to complete the Informed Consent process&#xD;
&#xD;
          -  Subjects with a history of keloid formation&#xD;
&#xD;
          -  History of lidocaine or Novocain allergy&#xD;
&#xD;
          -  Subjects with a systemic infection requiring a course of systemic antibiotics or&#xD;
             antivirals within the last 2 weeks&#xD;
&#xD;
          -  Subjects with MD diagnosed Type 1 or 2 diabetes mellitus&#xD;
&#xD;
          -  Subjects with NYHA class III or IV cardiac status&#xD;
&#xD;
          -  Subjects with a history of liver disease (EtOH, viral hepatitis, drug-induced&#xD;
             hepatitis or other)&#xD;
&#xD;
          -  Subjects with evidence of an underlying systemic disease based on history and physical&#xD;
             (other than the above diagnostic categories (and associated allergic disorders), or&#xD;
             well-controlled hypertension, or hyperlipidemia).&#xD;
&#xD;
          -  History of cancer other than nonmelanomatous skin cancer or cervical dysplasia&#xD;
&#xD;
          -  Participants enrolled while on a systemic treatment for their atopic dermatitis (e.g.&#xD;
             cyclosporine, mycophenolate mofetil) must remain on a stable dose for the duration of&#xD;
             the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lisa A Beck, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Rochester</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Rochester Medical Center</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2014</verification_date>
  <study_first_submitted>September 26, 2012</study_first_submitted>
  <study_first_submitted_qc>September 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 28, 2012</study_first_posted>
  <last_update_submitted>December 1, 2014</last_update_submitted>
  <last_update_submitted_qc>December 1, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 2, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Rochester</investigator_affiliation>
    <investigator_full_name>Lisa Beck</investigator_full_name>
    <investigator_title>Professor of Dermatology</investigator_title>
  </responsible_party>
  <keyword>atopic dermatitis</keyword>
  <keyword>eczema</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dermatitis, Atopic</mesh_term>
    <mesh_term>Dermatitis</mesh_term>
    <mesh_term>Eczema</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pioglitazone</mesh_term>
  </intervention_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/NCT01695707
org study id: RSRB00041078
secondary id: 1R21AR062357
nct id: NCT01695707
lead sponsor: 
collaborator: 
has dmc: Yes
Many patients with eczema (atopic dermatitis) have an inherent defect in their skin barrier
      as demonstrated by high water loss. In laboratory conditions, studies have shown that
      pioglitazone restores the skin barrier function in skin from eczema patients. The purpose of
      this study is to determine if taking pioglitazone improves the skin barrier function in
      people with eczema.
Enrolled patients will be randomized to either placebo or pioglitazone. Each randomized
      subject will have a skin biopsy and skin irritancy assay performed prior to treatment and at
      the end of 12 weeks of treatment. Noninvasive barrier measurements including transepidermal
      water loss will be recorded at all study visits.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Noninvasive barrier measurements (TEWL)
description: Transepidermal Water Loss (TEWL) will be measured at multiple time points throughout the study as a surrogate for skin barrier integrity.
measure: Transepithelial electrical resistance (TEER) and permeability
description: Skin biopsies will be performed twice during the study. The integrity of the skin barrier will be assessed in the lab by transepithelial electrical resistance (TEER) and permeability of the biopsy specimens.
measure: mRNA
description: Ex vivo assessment of mRNA expression of key epidermal barrier proteins will also be performed on the biopsy specimens.
measure: Skin Irritancy
description: The clinical efficacy of PIO will be assessed by quantifying the skin response to a model irritant, sodium lauryl sulphate (SLS) at several time points. Subjects will be exposed for 24 h on the dominant inner arm to SLS at three concentrations (wt/vol in water - 0.125, 0.5 and 2%) (Fluka) using standard patch test reagents (Finn chambers of 18-mm diam, Filter Discs & Scanpor tape). Before application and at several time points after removal, TEWL and erythema will be measured at the exposed site and at a control site. Erythema will be measured using a colorimeter (Minolta CR-200).
arm group label: Placebo
arm group type: Placebo Comparator
description: Subjects randomized to placebo will receive opaque size "00" gelatin capsules containing 240mg lactose. As with the intervention group, 1 capsule will be taken by each day throughout the treatment period.
arm group label: Pioglitazone
arm group type: Experimental
description: Subjects randomized to pioglitazone will receive opaque size "00" gelatin capsules containing pioglitazone. For the first 3 weeks, capsules will contain 30 mg pioglitazone. For the remaining 9 weeks of the treatment period, capsules will contain 45 mg pioglitazone unless subjects are unable to tolerate this increased dose.
One capsule will be taken by each day throughout the treatment period.
intervention type: Drug
intervention name: Pioglitazone
description: see Arm Description
arm group label: Pioglitazone
other name: Actos
intervention type: Drug
intervention name: Placebo (for pioglitazone)
description: see Arm Description
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: Lisa A Beck, MD
role: Principal Investigator
affiliation: University of Rochester
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Rochester
investigator full name: Lisa Beck
investigator title: Professor of Dermatology
mesh term: Dermatitis, Atopic
mesh term: Dermatitis
mesh term: Eczema
mesh term: Pioglitazone