<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/NCT02262832</url>
  </required_header>
  <id_info>
    <org_study_id>150003</org_study_id>
    <secondary_id>15-DK-0003</secondary_id>
    <nct_id>NCT02262832</nct_id>
  </id_info>
  <brief_title>Compassionate Use of Metreleptin in Previously Treated People With Generalized Lipodystrophy</brief_title>
  <official_title>Compassionate Use of Metreleptin in Previously-Treated Patients With Generalized Lipodystrophy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      - Generalized lipodystrophy can cause high blood fat levels and resistance to insulin. This&#xD;
      can lead to health problems including diabetes. Researchers have found that the drug&#xD;
      metreleptin improves health in people with this disease.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      - To test the safety and effectiveness of metreleptin.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
        -  People ages 6 months and older with generalized lipodystrophy who:&#xD;
&#xD;
        -  have received metreleptin through NIH studies AND&#xD;
&#xD;
        -  cannot get it through approved or compassionate use mechanisms in their home country.&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  Participants will come to NIH approximately every 6 months during year one, then every 1&#xD;
           2 years. Financial assistance may be available for travel within the U.S.&#xD;
&#xD;
        -  At visits, participants will get a supply of metreleptin to take home for daily&#xD;
           injections. They will have:&#xD;
&#xD;
        -  plastic catheter placed in an arm vein.&#xD;
&#xD;
        -  blood tests, urine collection, and physical exam.&#xD;
&#xD;
        -  oral glucose tolerance test, drinking a sweet liquid.&#xD;
&#xD;
        -  ultrasound of the heart, liver, uterus, and ovaries. A gel and a probe are placed on the&#xD;
           skin and pictures are taken of the organs.&#xD;
&#xD;
        -  echocardiogram, which takes pictures of the heart with sound waves.&#xD;
&#xD;
        -  Resting Metabolic Rate taken. A plastic hood is worn over the head while the oxygen they&#xD;
           breathe is measured.&#xD;
&#xD;
        -  Participants will have up to 3 DEXA scan x-rays per year.&#xD;
&#xD;
        -  Participants may have:&#xD;
&#xD;
        -  annual bone x-rays.&#xD;
&#xD;
        -  liver biopsies every few years. A needle will be inserted into the liver to obtain a&#xD;
           small piece. Participants will sign a separate consent for this.&#xD;
&#xD;
        -  Participants must be seen regularly by their local doctors and have blood tests at least&#xD;
           every 3 6 months at home.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Leptin is an adipocyte-derived hormone that can be thought of as a signal from adipose tissue&#xD;
      to the rest of the body conveying information about long-term nutritional status. Patients&#xD;
      with the very rare condition of generalized lipodystrophy have leptin deficiency secondary to&#xD;
      lack of adipose tissue. The combination of leptin deficiency and ectopic lipid deposition in&#xD;
      patients with lipodystrophy leads to metabolic complications including severe insulin&#xD;
      resistance and diabetes, hypertriglyceridemia, nonalcoholic steatohepatitis, and polycystic&#xD;
      ovarian syndrome. Between 2000 and 2014, the NIDDK IRP conducted an open-label clinical trial&#xD;
      of the recombinant human leptin analog, metreleptin, in patients with generalized and partial&#xD;
      forms of lipodystrophy. This study showed that metreleptin ameliorates metabolic and&#xD;
      endocrine abnormalities in lipodystrophy, including reducing food intake, improving insulin&#xD;
      resistance and diabetes, reducing ectopic lipid, and normalizing reproduction. Based on these&#xD;
      data, metreleptin was approved by the FDA in February, 2014, for patients with generalized,&#xD;
      but not partial, lipodystrophy.&#xD;
&#xD;
      Currently, metreleptin is not available as an approved drug outside the US and Japan, and it&#xD;
      is available on a compassionate use basis only in a few additional countries. The purpose of&#xD;
      this study is twofold:&#xD;
&#xD;
        1. To provide access to metreleptin to patients with generalized lipodystrophy, including&#xD;
           those who have previously received metreleptin through NIH studies (protocols 02-DK-0022&#xD;
           and 13-DK- 0057) AND/OR who cannot obtain metreleptin through approved or compassionate&#xD;
           use mechanisms in their home country&#xD;
&#xD;
        2. To continue to collect data on the long-term efficacy of metreleptin in ameliorating the&#xD;
           metabolic complications of generalized lipodystrophy.&#xD;
&#xD;
      Metreleptin will be given at doses of less than or equal to 0.24 mg/kg/day, adjusted based on&#xD;
      body weight and metabolic control. Patients will be seen approximately once per year at NIH&#xD;
      for evaluation, and potentially less frequently for those who are medically stable and have&#xD;
      difficulty traveling to the US. Laboratory evaluation will be obtained more frequently by the&#xD;
      patient s home providers as clinically indicated. The primary outcomes of the study are&#xD;
      improvements in serum triglycerides and hemoglobin A1c levels. Secondary outcomes include&#xD;
      measures of steatohepatitis and ectopic lipid, body composition, bone mineral density and&#xD;
      bone mineral metabolism, and pituitary and reproductive function.&#xD;
&#xD;
      Metreleptin is supplied by Amryt Pharma. Neither the NIH nor Amryt Pharma can guarantee that&#xD;
      leptin will be available for these patients indefinitely and/or after the study ends.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 9, 2014</start_date>
  <completion_date type="Anticipated">July 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">July 31, 2025</primary_completion_date>
  <phase>Phase 3</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>Serum triglycerides</measure>
    <time_frame>every 6-12 months</time_frame>
    <description>Improvements in lab value.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Serum hemoglobin A1C</measure>
    <time_frame>every 6-12 months</time_frame>
    <description>Improvements in lab value.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Steatohepatosis</measure>
    <time_frame>every 12 months</time_frame>
    <description>stable or improvements</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pituitary &amp;amp; Reproductive Function</measure>
    <time_frame>every 6-12 months</time_frame>
    <description>stable or improvements</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ectopic lipid &amp;amp; body composition</measure>
    <time_frame>every 12 months</time_frame>
    <description>stable or improvements</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bone mineral density &amp;amp; metabolism</measure>
    <time_frame>every 12 months</time_frame>
    <description>stable or improvements</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Lipodystrophy</condition>
  <condition>Diabetes</condition>
  <condition>Hyperlipidemia</condition>
  <arm_group>
    <arm_group_label>Leptin study drug</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Administration of study drug SQ BID</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metreleptin</intervention_name>
    <description>administered subcutaneously 1-2 times/day</description>
    <arm_group_label>Leptin study drug</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
               1. Age greater than or equal to 6 months.&#xD;
&#xD;
               2. Generalized lipodystrophy (either congenital or acquired).&#xD;
&#xD;
               3. Those who cannot obtain metreleptin through approved or compassionate use&#xD;
                  mechanisms in their home country.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          1. Availability of metreleptin to the patient either as an approved drug, or through&#xD;
             local compassionate use or expanded access programs.&#xD;
&#xD;
          2. Known HIV infection or HIV-associated lipodystrophy.&#xD;
&#xD;
          3. Any medical condition or medication that will increase risk to the subject.&#xD;
&#xD;
          4. Current alcohol or substance abuse.&#xD;
&#xD;
          5. Subjects who have a known hypersensitivity to E. coli derived proteins (as leptin is&#xD;
             derived from such proteins).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>98 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rebecca J Brown, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Megan S Startzell, R.N.</last_name>
    <phone>(301) 402-6371</phone>
    <email>megan.startzell@nih.gov</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Rebecca J Brown, M.D.</last_name>
    <phone>(301) 594-0609</phone>
    <email>brownrebecca@mail.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>TTY dial 711</phone_ext>
      <email>ccopr@nih.gov</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2015-DK-0003.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <reference>
    <citation>Malandrino N, Reynolds JC, Brychta RJ, Chen KY, Auh S, Gharib AM, Startzell M, Cochran EK, Brown RJ. Visceral fat does not contribute to metabolic disease in lipodystrophy. Obes Sci Pract. 2019 Jan 24;5(1):75-82. doi: 10.1002/osp4.319. eCollection 2019 Feb.</citation>
    <PMID>30847226</PMID>
  </reference>
  <reference>
    <citation>Meral R, Ryan BJ, Malandrino N, Jalal A, Neidert AH, Muniyappa R, Akinci B, Horowitz JF, Brown RJ, Oral EA. &quot;Fat Shadows&quot; From DXA for the Qualitative Assessment of Lipodystrophy: When a Picture Is Worth a Thousand Numbers. Diabetes Care. 2018 Oct;41(10):2255-2258. doi: 10.2337/dc18-0978.</citation>
    <PMID>30237235</PMID>
  </reference>
  <verification_date>September 11, 2023</verification_date>
  <study_first_submitted>October 10, 2014</study_first_submitted>
  <study_first_submitted_qc>October 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 13, 2014</study_first_posted>
  <last_update_submitted>September 14, 2023</last_update_submitted>
  <last_update_submitted_qc>September 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Diabetes</keyword>
  <keyword>Leptin</keyword>
  <keyword>Lipodystrophy</keyword>
  <keyword>Hypertriglyceridemia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lipodystrophy, Congenital Generalized</mesh_term>
    <mesh_term>Lipodystrophy</mesh_term>
    <mesh_term>Hyperlipidemias</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>.Subject level data will be shared upon request after appropriate collaboration agreements are in place.</ipd_description>
  </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/NCT02262832
org study id: 150003
secondary id: 15-DK-0003
nct id: NCT02262832
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
Background:

      - Generalized lipodystrophy can cause high blood fat levels and resistance to insulin. This
      can lead to health problems including diabetes. Researchers have found that the drug
      metreleptin improves health in people with this disease.

      Objective:

      - To test the safety and effectiveness of metreleptin.

      Eligibility:

        -  People ages 6 months and older with generalized lipodystrophy who:

        -  have received metreleptin through NIH studies AND

        -  cannot get it through approved or compassionate use mechanisms in their home country.

      Design:

        -  Participants will come to NIH approximately every 6 months during year one, then every 1
           2 years. Financial assistance may be available for travel within the U.S.

        -  At visits, participants will get a supply of metreleptin to take home for daily
           injections. They will have:

        -  plastic catheter placed in an arm vein.

        -  blood tests, urine collection, and physical exam.

        -  oral glucose tolerance test, drinking a sweet liquid.

        -  ultrasound of the heart, liver, uterus, and ovaries. A gel and a probe are placed on the
           skin and pictures are taken of the organs.

        -  echocardiogram, which takes pictures of the heart with sound waves.

        -  Resting Metabolic Rate taken. A plastic hood is worn over the head while the oxygen they
           breathe is measured.

        -  Participants will have up to 3 DEXA scan x-rays per year.

        -  Participants may have:

        -  annual bone x-rays.

        -  liver biopsies every few years. A needle will be inserted into the liver to obtain a
           small piece. Participants will sign a separate consent for this.

        -  Participants must be seen regularly by their local doctors and have blood tests at least
           every 3 6 months at home.
Leptin is an adipocyte-derived hormone that can be thought of as a signal from adipose tissue
      to the rest of the body conveying information about long-term nutritional status. Patients
      with the very rare condition of generalized lipodystrophy have leptin deficiency secondary to
      lack of adipose tissue. The combination of leptin deficiency and ectopic lipid deposition in
      patients with lipodystrophy leads to metabolic complications including severe insulin
      resistance and diabetes, hypertriglyceridemia, nonalcoholic steatohepatitis, and polycystic
      ovarian syndrome. Between 2000 and 2014, the NIDDK IRP conducted an open-label clinical trial
      of the recombinant human leptin analog, metreleptin, in patients with generalized and partial
      forms of lipodystrophy. This study showed that metreleptin ameliorates metabolic and
      endocrine abnormalities in lipodystrophy, including reducing food intake, improving insulin
      resistance and diabetes, reducing ectopic lipid, and normalizing reproduction. Based on these
      data, metreleptin was approved by the FDA in February, 2014, for patients with generalized,
      but not partial, lipodystrophy.

      Currently, metreleptin is not available as an approved drug outside the US and Japan, and it
      is available on a compassionate use basis only in a few additional countries. The purpose of
      this study is twofold:

        1. To provide access to metreleptin to patients with generalized lipodystrophy, including
           those who have previously received metreleptin through NIH studies (protocols 02-DK-0022
           and 13-DK- 0057) AND/OR who cannot obtain metreleptin through approved or compassionate
           use mechanisms in their home country

        2. To continue to collect data on the long-term efficacy of metreleptin in ameliorating the
           metabolic complications of generalized lipodystrophy.

      Metreleptin will be given at doses of less than or equal to 0.24 mg/kg/day, adjusted based on
      body weight and metabolic control. Patients will be seen approximately once per year at NIH
      for evaluation, and potentially less frequently for those who are medically stable and have
      difficulty traveling to the US. Laboratory evaluation will be obtained more frequently by the
      patient s home providers as clinically indicated. The primary outcomes of the study are
      improvements in serum triglycerides and hemoglobin A1c levels. Secondary outcomes include
      measures of steatohepatitis and ectopic lipid, body composition, bone mineral density and
      bone mineral metabolism, and pituitary and reproductive function.

      Metreleptin is supplied by Amryt Pharma. Neither the NIH nor Amryt Pharma can guarantee that
      leptin will be available for these patients indefinitely and/or after the study ends.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Serum triglycerides
time frame: every 6-12 months
description: Improvements in lab value.
measure: Serum hemoglobin A1C
time frame: every 6-12 months
description: Improvements in lab value.
measure: Steatohepatosis
time frame: every 12 months
description: stable or improvements
measure: Pituitary &amp; Reproductive Function
time frame: every 6-12 months
description: stable or improvements
measure: Ectopic lipid &amp; body composition
time frame: every 12 months
description: stable or improvements
measure: Bone mineral density &amp; metabolism
time frame: every 12 months
description: stable or improvements
arm group label: Leptin study drug
arm group type: Other
description: Administration of study drug SQ BID
intervention type: Drug
intervention name: Metreleptin
description: administered subcutaneously 1-2 times/day
arm group label: Leptin study drug
criteria: 
gender: All
minimum age: 6 Months
maximum age: 98 Years
healthy volunteers: No
last name: Rebecca J Brown, M.D.
role: Principal Investigator
affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
last name: Megan S Startzell, R.N.
phone: (301) 402-6371
email: megan.startzell@nih.gov
last name: Rebecca J Brown, M.D.
phone: (301) 594-0609
email: brownrebecca@mail.nih.gov
facility: 
status: Recruiting
contact: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2015-DK-0003.html
description: NIH Clinical Center Detailed Web Page
citation: Malandrino N, Reynolds JC, Brychta RJ, Chen KY, Auh S, Gharib AM, Startzell M, Cochran EK, Brown RJ. Visceral fat does not contribute to metabolic disease in lipodystrophy. Obes Sci Pract. 2019 Jan 24;5(1):75-82. doi: 10.1002/osp4.319. eCollection 2019 Feb.
PMID: 30847226
citation: Meral R, Ryan BJ, Malandrino N, Jalal A, Neidert AH, Muniyappa R, Akinci B, Horowitz JF, Brown RJ, Oral EA. "Fat Shadows" From DXA for the Qualitative Assessment of Lipodystrophy: When a Picture Is Worth a Thousand Numbers. Diabetes Care. 2018 Oct;41(10):2255-2258. doi: 10.2337/dc18-0978.
PMID: 30237235
responsible party type: Sponsor
mesh term: Lipodystrophy, Congenital Generalized
mesh term: Lipodystrophy
mesh term: Hyperlipidemias
sharing ipd: No
ipd description: .Subject level data will be shared upon request after appropriate collaboration agreements are in place.