<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/NCT02262806</url>
  </required_header>
  <id_info>
    <org_study_id>150002</org_study_id>
    <secondary_id>15-DK-0002</secondary_id>
    <nct_id>NCT02262806</nct_id>
  </id_info>
  <brief_title>Compassionate Use of Metreleptin in Previously Treated People With Partial Lipodystrophy</brief_title>
  <official_title>Compassionate Use of Metreleptin in Previously-Treated Patients With Partial 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;
      - Partial lipodystrophy can cause high blood fat levels and resistance to insulin. This can&#xD;
      lead to health problems including diabetes. Researchers have found that the drug metreleptin&#xD;
      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 age 6 months and older with partial lipodystrophy who&#xD;
&#xD;
        -  have received metreleptin through NIH studies and shown improvement AND&#xD;
&#xD;
        -  cannot get metreleptin other ways.&#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, or it can be shipped to them inside the U.S. 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 lipodystrophy have leptin deficiency secondary to lack of adipose tissue. The&#xD;
      combination of leptin deficiency and ectopic lipid deposition in patients with lipodystrophy&#xD;
      leads to metabolic complications including severe insulin resistance and diabetes,&#xD;
      hypertriglyceridemia, non-alcoholic steatohepatitis, and polycystic ovarian syndrome. Between&#xD;
      2000 and 2014, the NIDDK IRP conducted an open-label clinical trial of the recombinant human&#xD;
      leptin analog, metreleptin, in patients with generalized and partial forms of lipodystrophy.&#xD;
      This study showed that metreleptin ameliorates metabolic and endocrine abnormalities in&#xD;
      lipodystrophy, including reducing food intake, improving insulin resistance and diabetes,&#xD;
      reducing ectopic lipid, and normalizing reproduction. Based on these data, metreleptin was&#xD;
      approved by the FDA in February, 2014, for patients with generalized, but not partial,&#xD;
      lipodystrophy. Our data have shown, however, that a subgroup of patients with partial&#xD;
      lipodystrophy do gain medical benefit from metreleptin.&#xD;
&#xD;
      The purpose of this study is twofold:&#xD;
&#xD;
        -  To provide access to metreleptin to patients with partial lipodystrophy who have&#xD;
           previously received and derived benefit from metreleptin through NIH studies (protocols&#xD;
           02-DK-0022 and 13-DK-0057).&#xD;
&#xD;
        -  To continue to collect data on the long-term efficacy of metreleptin in ameliorating the&#xD;
           metabolic complications of partial 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 NIH. 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, Incorporated. Neither the NIH nor Amryt Pharma can&#xD;
      guarantee that leptin will be available indefinitely and/or after the study ends.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 14, 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 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>Serum hemoglobin A1C</measure>
    <time_frame>every 6-12 months</time_frame>
    <description>improvement in lab value</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Serum triglycerides</measure>
    <time_frame>every 6-12 months</time_frame>
    <description>improvement in lab value</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Diabetes</condition>
  <condition>Lipodystrophy</condition>
  <condition>Hyperlipidemia</condition>
  <arm_group>
    <arm_group_label>Leptin therapy</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>leptin administered via SC injections BID</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metreleptin</intervention_name>
    <description>A leptin analog indicated as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency in patients with partial lipodystrophy.</description>
    <arm_group_label>Leptin therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA&#xD;
&#xD;
          -  Age greater than or equal to 6 months&#xD;
&#xD;
          -  Partial lipodystrophy (either genetic or acquired)&#xD;
&#xD;
          -  Previously or currently treated with metreleptin under NIH study 02-DK-0022 and/or NIH&#xD;
             study 13-DK-0057.&#xD;
&#xD;
          -  Documented metabolic benefit from prior or current metreleptin treatment, defined as&#xD;
             one or more of the following:&#xD;
&#xD;
               -  TG reduction greater than or equal to 30% OR&#xD;
&#xD;
               -  HbA1c reduction greater than or equal to 1% OR&#xD;
&#xD;
               -  Decrease in insulin requirements greater than or equal to 40% OR&#xD;
&#xD;
               -  Decrease in episodes of pancreatitis OR&#xD;
&#xD;
               -  Improvement in steatohepatitis OR&#xD;
&#xD;
               -  Withdrawal of metreleptin led to marked worsening of metabolic parameters&#xD;
&#xD;
        EXCLUSION CRITERIA&#xD;
&#xD;
          -  Availability of metreleptin to the patient either as an approved drug, or through&#xD;
             local compassionate use or expanded access programs.&#xD;
&#xD;
          -  Known HIV infection or HIV-associated lipodystrophy.&#xD;
&#xD;
          -  Psychiatric disorder impeding competence or compliance.&#xD;
&#xD;
          -  Any medical condition or medication that will increase risk to the subject.&#xD;
&#xD;
          -  Current alcohol or substance abuse.&#xD;
&#xD;
          -  Subjects who have a known hypersensitivity to E. coli derived 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>
  <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>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2015-DK-0002.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <reference>
    <citation>Akinci B, Oral EA, Neidert A, Rus D, Cheng WY, Thompson-Leduc P, Cheung HC, Bradt P, Foss de Freitas MC, Montenegro RM, Fernandes VO, Cochran E, Brown RJ. Comorbidities and Survival in Patients With Lipodystrophy: An International Chart Review Study. J Clin Endocrinol Metab. 2019 Nov 1;104(11):5120-5135. doi: 10.1210/jc.2018-02730.</citation>
    <PMID>31314093</PMID>
  </reference>
  <verification_date>September 12, 2023</verification_date>
  <study_first_submitted>October 9, 2014</study_first_submitted>
  <study_first_submitted_qc>October 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 13, 2014</study_first_posted>
  <last_update_submitted>September 15, 2023</last_update_submitted>
  <last_update_submitted_qc>September 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Lipodystrophy</keyword>
  <keyword>Leptin</keyword>
  <keyword>Hypertriglyceridemia</keyword>
  <keyword>Diabetes</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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/NCT02262806
org study id: 150002
secondary id: 15-DK-0002
nct id: NCT02262806
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
Background:

      - Partial 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 age 6 months and older with partial lipodystrophy who

        -  have received metreleptin through NIH studies and shown improvement AND

        -  cannot get metreleptin other ways.

      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, or it can be shipped to them inside the U.S. 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 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, non-alcoholic 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. Our data have shown, however, that a subgroup of patients with partial
      lipodystrophy do gain medical benefit from metreleptin.

      The purpose of this study is twofold:

        -  To provide access to metreleptin to patients with partial lipodystrophy who have
           previously received and derived benefit from metreleptin through NIH studies (protocols
           02-DK-0022 and 13-DK-0057).

        -  To continue to collect data on the long-term efficacy of metreleptin in ameliorating the
           metabolic complications of partial 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 NIH. 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, Incorporated. Neither the NIH nor Amryt Pharma can
      guarantee that leptin will be available indefinitely and/or after the study ends.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Serum hemoglobin A1C
time frame: every 6-12 months
description: improvement in lab value
measure: Serum triglycerides
time frame: every 6-12 months
description: improvement in lab value
arm group label: Leptin therapy
arm group type: Other
description: leptin administered via SC injections BID
intervention type: Drug
intervention name: Metreleptin
description: A leptin analog indicated as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency in patients with partial lipodystrophy.
arm group label: Leptin therapy
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)
facility: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2015-DK-0002.html
description: NIH Clinical Center Detailed Web Page
citation: Akinci B, Oral EA, Neidert A, Rus D, Cheng WY, Thompson-Leduc P, Cheung HC, Bradt P, Foss de Freitas MC, Montenegro RM, Fernandes VO, Cochran E, Brown RJ. Comorbidities and Survival in Patients With Lipodystrophy: An International Chart Review Study. J Clin Endocrinol Metab. 2019 Nov 1;104(11):5120-5135. doi: 10.1210/jc.2018-02730.
PMID: 31314093
responsible party type: Sponsor
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.