<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/NCT03304678</url>
  </required_header>
  <id_info>
    <org_study_id>180003</org_study_id>
    <secondary_id>18-H-0003</secondary_id>
    <nct_id>NCT03304678</nct_id>
  </id_info>
  <brief_title>Discovery of Sirolimus Sensitive Biomarkers in Blood</brief_title>
  <official_title>Discovery of Sirolimus Sensitive Biomarkers in Blood</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      Lymphangioleiomyomatosis (LAM) is a rare, progressive disease. It usually affects women in&#xD;
      the prime of their lives. It typically results in lung destruction. Studies have shown that a&#xD;
      drug called sirolimus stabilizes lung function in people with LAM. But researchers do not&#xD;
      know what drug dose and blood serum levels are needed to reach this stability. Researchers&#xD;
      want to learn more about the right dose of sirolimus for people with LAM.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To determine if blood and urine markers after 1 dose and again after 3 months can be used to&#xD;
      evaluate the correct dose of sirolimus for people with LAM.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      Women ages 18-90 with LAM whose doctors have decided they should start taking sirolimus to&#xD;
      treat it.&#xD;
&#xD;
      Design:&#xD;
&#xD;
      At visit 1, participants will take their first dose of sirolimus by mouth at the clinic. They&#xD;
      will have blood and urine collected.&#xD;
&#xD;
      Participants will take 1 tablet of the study drug each day.&#xD;
&#xD;
      Visit 2 will be 3 months after visit 1. Participants will have blood and urine collected.&#xD;
&#xD;
      Participant samples will be stored in a secure place. No personal data will be connected to&#xD;
      them.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Sirolimus (rapamycin), which acts as a targeted inhibitor of the protein mechanistic target&#xD;
      of rapamycin (mTOR), has been shown to be effective in patients with lymphangioleiomyomatosis&#xD;
      (LAM). It stabilizes lung function, resolves chylous effusions and lymphangioleiomas and&#xD;
      shrinks angiomyolipomas. The current study is to understand better the short-term action of&#xD;
      the drug by following the effects on potential biomarkers in blood and urine. Patients with&#xD;
      LAM will have samples taken prior to administration of first dose of the drug, at 1 hr and&#xD;
      then at 23 hours after the drug (trough level). At 3 and 9 months, samples will be obtained&#xD;
      at trough and 1 hour after the dose. Molecular and cellular analyses will be performed to&#xD;
      look for potential biomarkers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 4, 2017</start_date>
  <completion_date type="Anticipated">September 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2024</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>to identify if miRNA are responsive to sirolimus in patients with LAM</measure>
    <time_frame>9 months</time_frame>
    <description>identify if miRNA are responsive to sirolimus in patients with LAM</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">26</enrollment>
  <condition>Lymphangioleiomyomatosis</condition>
  <arm_group>
    <arm_group_label>taking sirolimus</arm_group_label>
    <description>Subjects will come to the NIH and begin taking sirolimus 2mg</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with LAM, whose treating physicians have decided that they need to start treatment&#xD;
        with sirolimus will be referred to the NIH Clinical Center for these studies.@@@&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA&#xD;
&#xD;
          -  Female 18 to 90 years of age&#xD;
&#xD;
          -  Diagnosis of LAM&#xD;
&#xD;
          -  Initiation of sirolimus therapy (2mg daily) based on standard-of-care pulmonary&#xD;
             indications and the advice of the patient s local physician&#xD;
&#xD;
        EXCLUSION CRITERIA&#xD;
&#xD;
          -  Unable to travel to the NIH&#xD;
&#xD;
          -  Unable to provide informed consent&#xD;
&#xD;
          -  Advanced stage of a pulmonary or a systemic illness in which the risk of the study is&#xD;
             judged to be significant even in the absence of a clear contraindication to the&#xD;
             procedures&#xD;
&#xD;
          -  Women who are pregnant or lactating&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joel Moss, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Heart, Lung, and Blood Institute (NHLBI)</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Tatyana Worthy, R.N.</last_name>
    <phone>(301) 827-1376</phone>
    <email>worthyt@mail.nih.gov</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Joel Moss, M.D.</last_name>
    <phone>(301) 496-1597</phone>
    <email>mossj@nhlbi.nih.gov</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)</last_name>
      <phone>800-411-1222</phone>
      <phone_ext>TTY8664111010</phone_ext>
      <email>prpl@cc.nih.gov</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2018-H-0003.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <verification_date>May 3, 2023</verification_date>
  <study_first_submitted>October 6, 2017</study_first_submitted>
  <study_first_submitted_qc>October 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 9, 2017</study_first_posted>
  <last_update_submitted>May 4, 2023</last_update_submitted>
  <last_update_submitted_qc>May 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>mTORC1 Inhibition</keyword>
  <keyword>VEGF-D</keyword>
  <keyword>MicroRNA</keyword>
  <keyword>Natural History</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphangioleiomyomatosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03304678
org study id: 180003
secondary id: 18-H-0003
nct id: NCT03304678
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Background:

      Lymphangioleiomyomatosis (LAM) is a rare, progressive disease. It usually affects women in
      the prime of their lives. It typically results in lung destruction. Studies have shown that a
      drug called sirolimus stabilizes lung function in people with LAM. But researchers do not
      know what drug dose and blood serum levels are needed to reach this stability. Researchers
      want to learn more about the right dose of sirolimus for people with LAM.

      Objective:

      To determine if blood and urine markers after 1 dose and again after 3 months can be used to
      evaluate the correct dose of sirolimus for people with LAM.

      Eligibility:

      Women ages 18-90 with LAM whose doctors have decided they should start taking sirolimus to
      treat it.

      Design:

      At visit 1, participants will take their first dose of sirolimus by mouth at the clinic. They
      will have blood and urine collected.

      Participants will take 1 tablet of the study drug each day.

      Visit 2 will be 3 months after visit 1. Participants will have blood and urine collected.

      Participant samples will be stored in a secure place. No personal data will be connected to
      them.
Sirolimus (rapamycin), which acts as a targeted inhibitor of the protein mechanistic target
      of rapamycin (mTOR), has been shown to be effective in patients with lymphangioleiomyomatosis
      (LAM). It stabilizes lung function, resolves chylous effusions and lymphangioleiomas and
      shrinks angiomyolipomas. The current study is to understand better the short-term action of
      the drug by following the effects on potential biomarkers in blood and urine. Patients with
      LAM will have samples taken prior to administration of first dose of the drug, at 1 hr and
      then at 23 hours after the drug (trough level). At 3 and 9 months, samples will be obtained
      at trough and 1 hour after the dose. Molecular and cellular analyses will be performed to
      look for potential biomarkers.
observational model: Cohort
time perspective: Prospective
measure: to identify if miRNA are responsive to sirolimus in patients with LAM
time frame: 9 months
description: identify if miRNA are responsive to sirolimus in patients with LAM
arm group label: taking sirolimus
description: Subjects will come to the NIH and begin taking sirolimus 2mg
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
last name: Joel Moss, M.D.
role: Principal Investigator
affiliation: National Heart, Lung, and Blood Institute (NHLBI)
last name: Tatyana Worthy, R.N.
phone: (301) 827-1376
email: worthyt@mail.nih.gov
last name: Joel Moss, M.D.
phone: (301) 496-1597
email: mossj@nhlbi.nih.gov
facility: 
status: Recruiting
contact: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2018-H-0003.html
description: NIH Clinical Center Detailed Web Page
responsible party type: Sponsor
mesh term: Lymphangioleiomyomatosis
sharing ipd: Undecided