<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/NCT04409041</url>
  </required_header>
  <id_info>
    <org_study_id>201908021</org_study_id>
    <nct_id>NCT04409041</nct_id>
  </id_info>
  <brief_title>Oral Low-Dose Naltrexone for Lichen Planopilaris and Frontal Fibrosing Alopecia</brief_title>
  <official_title>Oral Low-Dose Naltrexone in the Treatment of Lichen Planopilaris and Frontal Fibrosing Alopecia; an Uncontrolled Open-label Prospective Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Washington University School of Medicine</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Oral naltrexone was initially FDA approved to treat opioid use disorder and alcohol&#xD;
      dependence at doses from 50-100mg/day. At lower doses of 1-5mg/day, naltrexone has been used&#xD;
      off-label with success in treatment of several dermatologic conditions including the scarring&#xD;
      hair loss disease lichen planopilaris. A recent case series of four patients with lichen&#xD;
      planopilaris and a subtype, frontal fibrosing alopecia, treated with oral low-dose naltrexone&#xD;
      at 3mg daily showed reduction of itch, clinical evidence of inflammation of the scalp, and of&#xD;
      disease progression. There were no reported adverse events.&#xD;
&#xD;
      Based on the promising evidence, we propose using low-dose naltrexone at a daily dose of 3mg&#xD;
      to treat lichen planopilaris and frontal fibrosing alopecia. The patients would be continued&#xD;
      on their other medications for these conditions. The study would be open-label, so all&#xD;
      participants would receive the low-dose naltrexone. Patients would be seen at 0,3,6 and 12&#xD;
      months to monitor their progress.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 1, 2019</start_date>
  <completion_date type="Actual">December 31, 2020</completion_date>
  <primary_completion_date type="Actual">December 31, 2020</primary_completion_date>
  <phase>Phase 2</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>Change in Patient-Reported Itch</measure>
    <time_frame>12 months</time_frame>
    <description>0-10 scale for itch. Lower scores are better outcome. A change between two time points is reported at 12 months.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Investigator Rated Erythema</measure>
    <time_frame>12 months</time_frame>
    <description>0-3 scale for erythema. Higher scores are worse. A change between two time points is reported at 12 months.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Patient Reported Burning/Pain</measure>
    <time_frame>12 months</time_frame>
    <description>Patient reported burning/pain on 0-10 scale. Higher values are worse. A change between two time points is reported at 12 months.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Investigator Rated Scale</measure>
    <time_frame>12 months</time_frame>
    <description>Investigator assessed outcome of scale on 0-3 scale. Higher numbers are worse. A change between two time points is reported at 12 months.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">43</enrollment>
  <condition>Lichen Planopilaris</condition>
  <condition>Frontal Fibrosing Alopecia</condition>
  <arm_group>
    <arm_group_label>Low-dose naltrexone group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All participants were prescribed low-dose naltrexone at 3mg oral daily.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Low-Dose Naltrexone</intervention_name>
    <description>Based on the promising evidence, we propose using low-dose naltrexone at a daily dose of 3mg to treat lichen planopilaris and frontal fibrosing alopecia. The patients would be continued on their other medications for these conditions. The study would be open-label, so all participants would receive the low-dose naltrexone. Patients would be seen at 0,3,6 and 12 months to monitor their progress.</description>
    <arm_group_label>Low-dose naltrexone group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults age 18 or greater&#xD;
&#xD;
          -  clinically or histologically confirmed diagnosis of lichen planopilaris or frontal&#xD;
             fibrosing alopecia&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  known allergy or hypersensitivity to naltrexone&#xD;
&#xD;
          -  patients with concurrent use of opioids&#xD;
&#xD;
          -  active depression, schizophrenia, and bipolar disorder&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Washington University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>May 22, 2020</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 1, 2020</study_first_posted>
  <results_first_submitted>October 21, 2021</results_first_submitted>
  <results_first_submitted_qc>November 29, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">December 30, 2021</results_first_posted>
  <last_update_submitted>November 29, 2021</last_update_submitted>
  <last_update_submitted_qc>November 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 30, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alopecia</mesh_term>
    <mesh_term>Alopecia Areata</mesh_term>
    <mesh_term>Lichen Planus</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Naltrexone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 7, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/41/NCT04409041/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Treatment Group (Low-dose Naltrexone)</title>
          <description>Everyone enrolled received low-dose naltrexone at 3mg oral daily.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="43"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>43 patients enrolled.</population>
      <group_list>
        <group group_id="B1">
          <title>Treatment Group (Low-dose Naltrexone)</title>
          <description>Everyone enrolled received low-dose naltrexone at 3mg oral daily.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="43"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="65" spread="10.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="41"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="43"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="41"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Patient-Reported Itch</title>
        <description>0-10 scale for itch. Lower scores are better outcome. A change between two time points is reported at 12 months.</description>
        <time_frame>12 months</time_frame>
        <population>Per protocol group</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group (Low-dose Naltrexone)</title>
            <description>Everyone enrolled received low-dose naltrexone at 3mg oral daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Patient-Reported Itch</title>
          <description>0-10 scale for itch. Lower scores are better outcome. A change between two time points is reported at 12 months.</description>
          <population>Per protocol group</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.33" lower_limit="-1.08" upper_limit="0.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Investigator Rated Erythema</title>
        <description>0-3 scale for erythema. Higher scores are worse. A change between two time points is reported at 12 months.</description>
        <time_frame>12 months</time_frame>
        <population>Per protocol group</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group (Low-dose Naltrexone)</title>
            <description>Everyone enrolled received low-dose naltrexone at 3mg oral daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Investigator Rated Erythema</title>
          <description>0-3 scale for erythema. Higher scores are worse. A change between two time points is reported at 12 months.</description>
          <population>Per protocol group</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.93" lower_limit="-1.32" upper_limit="-0.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Patient Reported Burning/Pain</title>
        <description>Patient reported burning/pain on 0-10 scale. Higher values are worse. A change between two time points is reported at 12 months.</description>
        <time_frame>12 months</time_frame>
        <population>Per protocol group</population>
        <group_list>
          <group group_id="O1">
            <title>Low-dose Naltrexone Group</title>
            <description>All participants were prescribed low-dose naltrexone at 3mg oral daily.&#xD;
Low-Dose Naltrexone: Based on the promising evidence, we propose using low-dose naltrexone at a daily dose of 3mg to treat lichen planopilaris and frontal fibrosing alopecia. The patients would be continued on their other medications for these conditions. The study would be open-label, so all participants would receive the low-dose naltrexone. Patients would be seen at 0,3,6 and 12 months to monitor their progress.</description>
          </group>
        </group_list>
        <measure>
          <title>Patient Reported Burning/Pain</title>
          <description>Patient reported burning/pain on 0-10 scale. Higher values are worse. A change between two time points is reported at 12 months.</description>
          <population>Per protocol group</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.50" lower_limit="-1.02" upper_limit="0.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Investigator Rated Scale</title>
        <description>Investigator assessed outcome of scale on 0-3 scale. Higher numbers are worse. A change between two time points is reported at 12 months.</description>
        <time_frame>12 months</time_frame>
        <population>Per protocol group</population>
        <group_list>
          <group group_id="O1">
            <title>Low-dose Naltrexone Group</title>
            <description>All participants were prescribed low-dose naltrexone at 3mg oral daily.&#xD;
Low-Dose Naltrexone: Based on the promising evidence, we propose using low-dose naltrexone at a daily dose of 3mg to treat lichen planopilaris and frontal fibrosing alopecia. The patients would be continued on their other medications for these conditions. The study would be open-label, so all participants would receive the low-dose naltrexone. Patients would be seen at 0,3,6 and 12 months to monitor their progress.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Investigator Rated Scale</title>
          <description>Investigator assessed outcome of scale on 0-3 scale. Higher numbers are worse. A change between two time points is reported at 12 months.</description>
          <population>Per protocol group</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.33" lower_limit="-0.72" upper_limit="0.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>12 months.</time_frame>
      <desc>Adverse events collected for the 12-month study period. There was no control group. 34 patients received at least one dose of naltrexone and were assessed for adverse events (however only 26 patients had follow up assessments that allowed them to be included in the efficacy analysis for primary outcomes).</desc>
      <group_list>
        <group group_id="E1">
          <title>Treatment Group (Low-dose Naltrexone)</title>
          <description>Everyone enrolled received low-dose naltrexone at 3mg oral daily.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Breast cancer</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>vivid dreams</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>headache</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Caroline Mann</name_or_title>
      <organization>Washington University</organization>
      <phone>(314) 996-8010</phone>
      <email>cmann@wustl.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT04409041
org study id: 201908021
nct id: NCT04409041
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Oral naltrexone was initially FDA approved to treat opioid use disorder and alcohol
      dependence at doses from 50-100mg/day. At lower doses of 1-5mg/day, naltrexone has been used
      off-label with success in treatment of several dermatologic conditions including the scarring
      hair loss disease lichen planopilaris. A recent case series of four patients with lichen
      planopilaris and a subtype, frontal fibrosing alopecia, treated with oral low-dose naltrexone
      at 3mg daily showed reduction of itch, clinical evidence of inflammation of the scalp, and of
      disease progression. There were no reported adverse events.

      Based on the promising evidence, we propose using low-dose naltrexone at a daily dose of 3mg
      to treat lichen planopilaris and frontal fibrosing alopecia. The patients would be continued
      on their other medications for these conditions. The study would be open-label, so all
      participants would receive the low-dose naltrexone. Patients would be seen at 0,3,6 and 12
      months to monitor their progress.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Patient-Reported Itch
time frame: 12 months
description: 0-10 scale for itch. Lower scores are better outcome. A change between two time points is reported at 12 months.
measure: Change in Investigator Rated Erythema
time frame: 12 months
description: 0-3 scale for erythema. Higher scores are worse. A change between two time points is reported at 12 months.
measure: Patient Reported Burning/Pain
time frame: 12 months
description: Patient reported burning/pain on 0-10 scale. Higher values are worse. A change between two time points is reported at 12 months.
measure: Change in Investigator Rated Scale
time frame: 12 months
description: Investigator assessed outcome of scale on 0-3 scale. Higher numbers are worse. A change between two time points is reported at 12 months.
arm group label: Low-dose naltrexone group
arm group type: Experimental
description: All participants were prescribed low-dose naltrexone at 3mg oral daily.
intervention type: Drug
intervention name: Low-Dose Naltrexone
description: Based on the promising evidence, we propose using low-dose naltrexone at a daily dose of 3mg to treat lichen planopilaris and frontal fibrosing alopecia. The patients would be continued on their other medications for these conditions. The study would be open-label, so all participants would receive the low-dose naltrexone. Patients would be seen at 0,3,6 and 12 months to monitor their progress.
arm group label: Low-dose naltrexone group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Sponsor
mesh term: Alopecia
mesh term: Alopecia Areata
mesh term: Lichen Planus
mesh term: Naltrexone
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 