<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/NCT01727440</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00030862</org_study_id>
    <nct_id>NCT01727440</nct_id>
  </id_info>
  <brief_title>Identifying the Genetic Predictors of Severe Acne Vulgaris and the Outcome of Oral Isotretinoin Treatment</brief_title>
  <acronym>SA</acronym>
  <official_title>Identifying the Genetic Predictors of Severe Acne Vulgaris and the Outcome of Oral Isotretinoin Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of this study is to enroll 250 participants that have joined the MURDOCK Study&#xD;
      Horizon 1.5 (Duke IRB Pro00011196) with a current or prior diagnosis of severe acne AND&#xD;
      current or prior treatment with oral isotretinoin. All 250 participants will answer a 5-page&#xD;
      questionnaire designed to collect information on the diagnosis of severe acne and response to&#xD;
      oral isotretinoin treatment. The aim is to identify genetic predictors of severe acne&#xD;
      vulgaris and the outcome of oral isotretinoin treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Acne vulgaris is an under-studied common genetic disease with tremendous economic&#xD;
      consequences. Acne vulgaris is one of the most common skin conditions treated by doctors. It&#xD;
      affects 40-50 million people in the USA, with prevalence as high as 85% (recent study from&#xD;
      Iran was 93%) in teenagers; 18% of woman have late onset (&gt;25yr) acne vulgaris. Severe acne&#xD;
      has a life-long psychosocial impact due to the significant scarring. Severe acne can also be&#xD;
      associated with severe systemic inflammatory disease with fever, sterile osteomyelitis,&#xD;
      inflammatory arthritis and other signs of systemic inflammatory responses. Some of these&#xD;
      syndromes in Mendelian form (e.g. PAPA syndrome) have known genetic defects. Finally, while&#xD;
      the data are inconclusive, there have been many suggestions that diet can exacerbate acne in&#xD;
      some patients. The standard of care treatment for severe acne is systemic retinoid therapy,&#xD;
      which, is usually, but not always effective. Unfortunately, systemic retinoid treatment is&#xD;
      associated with significant toxicity, including common cutaneous adverse effects (dry lips,&#xD;
      eyes, skin fragility), less common laboratory abnormalities such as elevated blood lipids,&#xD;
      liver function abnormalities, and severe predictable teratogenicity. In addition, systemic&#xD;
      therapy with retinoids has been associated with systemic diseases such as clinical&#xD;
      depression, suicide, and inflammatory bowel disease, however the mechanisms and significance&#xD;
      of these associations has not been determined. Given the frequency and severity of severe&#xD;
      acne, the predictable severe toxicity of systemic retinoid therapy, and the already&#xD;
      demonstrated genetic associations found in Mendelian forms of severe acne, it seems likely&#xD;
      that significant genetic risk factors may be identified in patients with severe acne which&#xD;
      would promote new and safer therapy, including dietary adjustment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2011</start_date>
  <completion_date type="Actual">August 2015</completion_date>
  <primary_completion_date type="Actual">August 2015</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Therapeutic response to isotretinoin</measure>
    <time_frame>10 months</time_frame>
    <description>All 250 patients with severe acne will be genotyped using the Illumina 610 BeadChip. Whole-exome sequencing will be performed on 100 extremely severe acne vulgaris patients, selected based on severity and response to oral isotretinoin treatment. A case-control GWAS analysis will be performed (250 recruited patients vs. 1000 normal controls of convenience available in other studies at CHGV). Additionally, an association analyses will be conducted using complete exome sequencing data for the most severe cases, compared with controls of convenience (as an extreme trait in the population, there is a reasonable expectation of discovery of any important variants, rare or common). This analysis would also include targeted analysis on available drug response data (efficacy and adverse response).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse reaccion to isotretinoin</measure>
    <time_frame>10 months</time_frame>
    <description>All 250 patients with severe acne will be genotyped using the Illumina 610 BeadChip. Whole-exome sequencing will be performed on 100 extremely severe acne vulgaris patients, selected based on severity and response to oral isotretinoin treatment. A case-control GWAS analysis will be performed (250 recruited patients vs. 1000 normal controls of convenience available in other studies at CHGV). Additionally, an association analyses will be conducted using complete exome sequencing data for the most severe cases, compared with controls of convenience (as an extreme trait in the population, there is a reasonable expectation of discovery of any important variants, rare or common). This analysis would also include targeted analysis on available drug response data (efficacy and adverse response).</description>
  </secondary_outcome>
  <enrollment type="Actual">123</enrollment>
  <condition>Acne Vulgaris</condition>
  <condition>Isotretinoin</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Whole blood collected in three 2-mL EDTA tubes&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Participants must enroll or have enrolled in the MURDOCK Study Community Registry and&#xD;
        Biorepository prior to joining this Severe Acne Study. At the MURDOCK Study visit, or after&#xD;
        the participant has enrolled in the MURDOCK Study, they will be asked (either in person or&#xD;
        via phone) if they would be willing to join the Severe Acne Study.&#xD;
&#xD;
        Participants between ages 12 and 18 may also join the MURDOCK Study if they meet the&#xD;
        eligibility criteria for this Severe Acne Study (a pediatric consent form will be used).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosed with severe acne while age &gt; 12 and &lt; 18, and&#xD;
&#xD;
          -  Completed at least one course of oral isotretinoin treatment; OR started treatment but&#xD;
             discontinued prior to completion due to adverse side effects (with the exception of&#xD;
             dry skin - see &quot;exclusion criteria&quot;); OR are currently undergoing and plan to complete&#xD;
             treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who are not willing to participate in this study&#xD;
&#xD;
          -  Patients who experienced inflammatory bowel disease (IBD) prior to oral isotretinoin&#xD;
             treatment&#xD;
&#xD;
          -  Patients who did not complete the oral isotretinoin treatment because of pregnancy,&#xD;
             dry skin, or reasons other than adverse side effects listed above&#xD;
&#xD;
          -  Patients who are not willing to or cannot provide a blood sample for Murdock Study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Russell Hall, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke Medicine Site Based Research Group</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Carolinas Medical Center Northeast Medical Arts Building</name>
      <address>
        <city>Concord</city>
        <state>North Carolina</state>
        <zip>28025</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dermatology Group of the Carolinas</name>
      <address>
        <city>Concord</city>
        <state>North Carolina</state>
        <zip>28025</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ada Jenkins Center</name>
      <address>
        <city>Davidson</city>
        <state>North Carolina</state>
        <zip>28036</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Harrisburg Sleep Center</name>
      <address>
        <city>Harrisburg</city>
        <state>North Carolina</state>
        <zip>28075</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lake Norman Community Health Clinic</name>
      <address>
        <city>Huntersville</city>
        <state>North Carolina</state>
        <zip>28078</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kannapolis Internal Medicine</name>
      <address>
        <city>Kannapolis</city>
        <state>North Carolina</state>
        <zip>28081</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.murdock-study.com/new-studies/severe-acne</url>
    <description>Murdock Study Severe Acne Study</description>
  </link>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>October 24, 2012</study_first_submitted>
  <study_first_submitted_qc>November 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 16, 2012</study_first_posted>
  <last_update_submitted>August 23, 2017</last_update_submitted>
  <last_update_submitted_qc>August 23, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 24, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>severe acne</keyword>
  <keyword>severe acne vulgaris</keyword>
  <keyword>acne</keyword>
  <keyword>acne vulgaris</keyword>
  <keyword>isotretinoin</keyword>
  <keyword>Accutane</keyword>
  <keyword>Sortret</keyword>
  <keyword>Amnesteem</keyword>
  <keyword>Claravis</keyword>
  <keyword>Clarus</keyword>
  <keyword>Decutan</keyword>
  <keyword>Isotane</keyword>
  <keyword>Izotek</keyword>
  <keyword>Oratane</keyword>
  <keyword>Isotret</keyword>
  <keyword>Roaccutane</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acne Vulgaris</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/NCT01727440
org study id: Pro00030862
nct id: NCT01727440
lead sponsor: 
has dmc: Yes
The goal of this study is to enroll 250 participants that have joined the MURDOCK Study
      Horizon 1.5 (Duke IRB Pro00011196) with a current or prior diagnosis of severe acne AND
      current or prior treatment with oral isotretinoin. All 250 participants will answer a 5-page
      questionnaire designed to collect information on the diagnosis of severe acne and response to
      oral isotretinoin treatment. The aim is to identify genetic predictors of severe acne
      vulgaris and the outcome of oral isotretinoin treatment.
Acne vulgaris is an under-studied common genetic disease with tremendous economic
      consequences. Acne vulgaris is one of the most common skin conditions treated by doctors. It
      affects 40-50 million people in the USA, with prevalence as high as 85% (recent study from
      Iran was 93%) in teenagers; 18% of woman have late onset (>25yr) acne vulgaris. Severe acne
      has a life-long psychosocial impact due to the significant scarring. Severe acne can also be
      associated with severe systemic inflammatory disease with fever, sterile osteomyelitis,
      inflammatory arthritis and other signs of systemic inflammatory responses. Some of these
      syndromes in Mendelian form (e.g. PAPA syndrome) have known genetic defects. Finally, while
      the data are inconclusive, there have been many suggestions that diet can exacerbate acne in
      some patients. The standard of care treatment for severe acne is systemic retinoid therapy,
      which, is usually, but not always effective. Unfortunately, systemic retinoid treatment is
      associated with significant toxicity, including common cutaneous adverse effects (dry lips,
      eyes, skin fragility), less common laboratory abnormalities such as elevated blood lipids,
      liver function abnormalities, and severe predictable teratogenicity. In addition, systemic
      therapy with retinoids has been associated with systemic diseases such as clinical
      depression, suicide, and inflammatory bowel disease, however the mechanisms and significance
      of these associations has not been determined. Given the frequency and severity of severe
      acne, the predictable severe toxicity of systemic retinoid therapy, and the already
      demonstrated genetic associations found in Mendelian forms of severe acne, it seems likely
      that significant genetic risk factors may be identified in patients with severe acne which
      would promote new and safer therapy, including dietary adjustment.
observational model: Case-Control
time perspective: Retrospective
measure: Therapeutic response to isotretinoin
time frame: 10 months
description: All 250 patients with severe acne will be genotyped using the Illumina 610 BeadChip. Whole-exome sequencing will be performed on 100 extremely severe acne vulgaris patients, selected based on severity and response to oral isotretinoin treatment. A case-control GWAS analysis will be performed (250 recruited patients vs. 1000 normal controls of convenience available in other studies at CHGV). Additionally, an association analyses will be conducted using complete exome sequencing data for the most severe cases, compared with controls of convenience (as an extreme trait in the population, there is a reasonable expectation of discovery of any important variants, rare or common). This analysis would also include targeted analysis on available drug response data (efficacy and adverse response).
measure: Adverse reaccion to isotretinoin
time frame: 10 months
description: All 250 patients with severe acne will be genotyped using the Illumina 610 BeadChip. Whole-exome sequencing will be performed on 100 extremely severe acne vulgaris patients, selected based on severity and response to oral isotretinoin treatment. A case-control GWAS analysis will be performed (250 recruited patients vs. 1000 normal controls of convenience available in other studies at CHGV). Additionally, an association analyses will be conducted using complete exome sequencing data for the most severe cases, compared with controls of convenience (as an extreme trait in the population, there is a reasonable expectation of discovery of any important variants, rare or common). This analysis would also include targeted analysis on available drug response data (efficacy and adverse response).
Whole blood collected in three 2-mL EDTA tubes
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 12 Years
maximum age: N/A
healthy volunteers: No
last name: Russell Hall, MD
role: Principal Investigator
affiliation: Duke Medicine Site Based Research Group
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://www.murdock-study.com/new-studies/severe-acne
description: Murdock Study Severe Acne Study
responsible party type: Sponsor
mesh term: Acne Vulgaris