<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/NCT03271034</url>
  </required_header>
  <id_info>
    <org_study_id>201702107</org_study_id>
    <nct_id>NCT03271034</nct_id>
  </id_info>
  <brief_title>Effect of Weight Loss on Body Composition and Metabolic Function in Women With Lipedema</brief_title>
  <acronym>Lipedema</acronym>
  <official_title>Effect of Weight Loss on Body Composition and Metabolic Function in Women With Lipedema</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>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Lipedema is a disorder characterized by massive, bilateral accumulation of fat below the&#xD;
      waist and in the legs. Enlargement of the lower extremities is often accompanied by leg pain&#xD;
      and accumulation of fluid. Little is known about the functional changes that lead to fat&#xD;
      accumulation and pain in women with lipedema. The goals of this project are to conduct a&#xD;
      comprehensive characterization of abdominal and femoral fat tissues in lean and obese women&#xD;
      with lipedema and to evaluate the potential effect of diet-induced weight loss as a therapy.&#xD;
&#xD;
      Once enrolled in the study, the following tests will be conducted on lean women with&#xD;
      lipedema: characterization of body composition (fat tissue distribution), insulin sensitivity&#xD;
      (response to insulin) and adipose tissue biology. The following tests will be conducted on&#xD;
      obese women with lipedema: characterization of body composition (fat tissue distribution),&#xD;
      insulin sensitivity (response to insulin), adipose tissue biology, and immune system&#xD;
      function/inflammation. As control, we will have BMI-matched women that are metabolically&#xD;
      normal lean (MNL), metabolically normal obese (MNO) and metabolically abnormal obese (MAO)&#xD;
      already analyzed in different studies at Washington University (IRB# 201512086). MNL, MAO and&#xD;
      MNO subjects underwent the same testing described above for the lipedema. Therefore, we will&#xD;
      use the data generated from IRB# 201512086 as comparison groups in the statistical analysis&#xD;
      to understand differences and similarities between lipedema and obesity.&#xD;
&#xD;
      A second aim of the study is to determine the effect of diet-induced weight loss on body&#xD;
      composition, insulin sensitivity, and adipose tissue biology in women with lipedema. The&#xD;
      results from this second aim of the study will hopefully provide important insights on the&#xD;
      efficacy of diet therapy in managing lipedema.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Once informed consent has been obtained, participants will complete 1 screening visit.&#xD;
&#xD;
      The screening visit includes a medical history, physical examination, pregnancy test (for&#xD;
      women of childbearing potential), blood tests, urine drug test, an oral glucose tolerance&#xD;
      test, resting electrocardiogram (ECG), and questionnaires.&#xD;
&#xD;
      Baseline testing will be performed in 2 visits requiring 1 inpatient overnight stay and will&#xD;
      require approximately 30 hours in total to complete testing. Testing will include imaging&#xD;
      scans to determine thigh fat mass; abdominal (belly) fat mass and liver fat content; DXA scan&#xD;
      to assess whole-body and leg fat mass; blood samples; hyperinsulinemic-euglycemic clamp&#xD;
      procedure; immune system function/inflammation (performed exclusively in people with obesity&#xD;
      and lipedema and BMI-matched controls); and adipose tissue (fat) biopsies.&#xD;
&#xD;
      Once Baseline Testing is completed, participants will start 5-10% dietitian and/or&#xD;
      behaviorist guided weight-loss for about 4 to 6 months.&#xD;
&#xD;
      Participant will keep a food diary and have weekly visits (in person or remote) with a study&#xD;
      dietitian and/or behaviorist.&#xD;
&#xD;
      After weight loss, the testing completed during baseline will be repeated.&#xD;
&#xD;
      Study procedures:&#xD;
&#xD;
        1. Medical history &amp; physical exam&#xD;
&#xD;
        2. Urine drug/pregnancy Test&#xD;
&#xD;
        3. Blood pressure, pulse, height, weight&#xD;
&#xD;
        4. Electrocardiogram (ECG)&#xD;
&#xD;
        5. Blood tests for routine lab analyses&#xD;
&#xD;
        6. Oral glucose tolerance test (OGTT)&#xD;
&#xD;
        7. Screening Questionnaires&#xD;
&#xD;
        8. Dual energy X-ray absorptiometry (DXA) scan to assess whole-body and leg fat mass&#xD;
&#xD;
        9. Magnetic Resonance Imaging (MRI) for Body Composition to determine the amount of fat in&#xD;
           the liver, abdomen (belly), and thigh.&#xD;
&#xD;
       10. Metabolism study (hyperinsulinemic-euglycemic clamp procedure) to assess how well&#xD;
           insulin works to control blood glucose (sugar) concentrations.&#xD;
&#xD;
       11. Abdominal (belly) and thigh fat biopsies&#xD;
&#xD;
       12. Immune function (performed in obese with lipedema subjects and BMI-matched controls).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 1, 2017</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Anticipated">June 2024</primary_completion_date>
  <phase>N/A</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>Body Composition and Fat distribution</measure>
    <time_frame>6 months</time_frame>
    <description>total body, upper and lower body fat masses, ii) intra-abdominal fat, and iii) intrahepatic triglyceride content</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Metabolic function insulin sensitivity</measure>
    <time_frame>7 months</time_frame>
    <description>multi-organ (liver, skeletal muscle and adipose tissue) insulin sensitivity</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Metabolic function</measure>
    <time_frame>6 months</time_frame>
    <description>β-cell function.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Immune system function (obese women with lipedema and BMI-matched controls)</measure>
    <time_frame>6 months</time_frame>
    <description>upper and lower body subcutaneous adipose tissue stromal vascular fraction content of immune cells; and ii) upper and lower body subcutaneous adipose tissue gene expression of markers of inflammation.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Lipedema</condition>
  <condition>Metabolism</condition>
  <arm_group>
    <arm_group_label>Baseline Lipedema characterization</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Body composition and Fat distribution, adipose tissue biology, metabolic and immune function in women with Lipedema. Participants will receive a low-calorie diet therapy in the form of low calorie meals or shakes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Weight loss</intervention_name>
    <description>Participants will lose weight by utilizing a low caloric diet and meeting with a study dietitian and/or behaviorist weekly for ~4 months.</description>
    <arm_group_label>Baseline Lipedema characterization</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of Lipedema&#xD;
&#xD;
          -  Lean women with lipedema (BMI &gt;19.5 kg/m² and &lt;26.0 kg/m²)&#xD;
&#xD;
          -  Women with obesity and lipedema (BMI &gt;30.0 kg/m² and &lt;50.0 kg/m²)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Medical, surgical or biological menopause&#xD;
&#xD;
          -  Previous bariatric surgery&#xD;
&#xD;
          -  Diagnosis of Type 2 Diabetes&#xD;
&#xD;
          -  HbA1C &lt;5.7%&#xD;
&#xD;
          -  Structured exercise &gt;2 days/week for ≥35 minutes of intense exercise (e.g., jogging,&#xD;
             activity that cause heavy breathing and sweating) or ≥150 minutes per week of&#xD;
             structured exercise (e.g., brisk walking)&#xD;
&#xD;
          -  Unstable weight (&gt;4% change in weight during the last 2 months before entering the&#xD;
             study)&#xD;
&#xD;
          -  Significant organ system dysfunction (e.g., diabetes, severe pulmonary, kidney or&#xD;
             cardiovascular disease)&#xD;
&#xD;
          -  Cancer or cancer that has been in remission for &lt;5 years&#xD;
&#xD;
          -  Polycystic Ovary Syndrome&#xD;
&#xD;
          -  Major psychiatric illness&#xD;
&#xD;
          -  Conditions that render participant unable to complete all testing procedures (e.g.,&#xD;
             severe ambulatory impairments, limb amputations, or metal implants that interfere with&#xD;
             imaging procedures; coagulation disorders)&#xD;
&#xD;
          -  Use of medications that are known to affect the study outcome measures (e.g.,&#xD;
             steroids, non-statin lipid-lowering medications) or increase the risk of study&#xD;
             procedures (e.g., anticoagulants) and that cannot be temporarily discontinued for this&#xD;
             study&#xD;
&#xD;
          -  Smoke cigarettes &gt;10 cigarettes/week&#xD;
&#xD;
          -  Consume &gt;14 units of alcohol per week&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Persons who are not able to grant voluntary informed consent&#xD;
&#xD;
          -  Persons who are unable or unwilling to follow the study protocol or who, for any&#xD;
             reason, the research team considers not an appropriate candidate for this study,&#xD;
             including non-compliance with screening appointments or study visits.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>68 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Samuel Klein, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Johanna Sonnenschein</last_name>
    <phone>314-747-2627</phone>
    <email>j.sonnenschein@wustl.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Janet Winkelmann</last_name>
    </contact>
    <investigator>
      <last_name>Samuel Klein, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Vincenza Cifarelli, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>August 29, 2017</study_first_submitted>
  <study_first_submitted_qc>August 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 1, 2017</study_first_posted>
  <last_update_submitted>August 4, 2023</last_update_submitted>
  <last_update_submitted_qc>August 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Lipedema</keyword>
  <keyword>Metabolism</keyword>
  <keyword>Body Composition</keyword>
  <keyword>Fat Distribution</keyword>
  <keyword>Immunology</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lipedema</mesh_term>
    <mesh_term>Weight Loss</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/NCT03271034
org study id: 201702107
nct id: NCT03271034
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Lipedema is a disorder characterized by massive, bilateral accumulation of fat below the
      waist and in the legs. Enlargement of the lower extremities is often accompanied by leg pain
      and accumulation of fluid. Little is known about the functional changes that lead to fat
      accumulation and pain in women with lipedema. The goals of this project are to conduct a
      comprehensive characterization of abdominal and femoral fat tissues in lean and obese women
      with lipedema and to evaluate the potential effect of diet-induced weight loss as a therapy.

      Once enrolled in the study, the following tests will be conducted on lean women with
      lipedema: characterization of body composition (fat tissue distribution), insulin sensitivity
      (response to insulin) and adipose tissue biology. The following tests will be conducted on
      obese women with lipedema: characterization of body composition (fat tissue distribution),
      insulin sensitivity (response to insulin), adipose tissue biology, and immune system
      function/inflammation. As control, we will have BMI-matched women that are metabolically
      normal lean (MNL), metabolically normal obese (MNO) and metabolically abnormal obese (MAO)
      already analyzed in different studies at Washington University (IRB# 201512086). MNL, MAO and
      MNO subjects underwent the same testing described above for the lipedema. Therefore, we will
      use the data generated from IRB# 201512086 as comparison groups in the statistical analysis
      to understand differences and similarities between lipedema and obesity.

      A second aim of the study is to determine the effect of diet-induced weight loss on body
      composition, insulin sensitivity, and adipose tissue biology in women with lipedema. The
      results from this second aim of the study will hopefully provide important insights on the
      efficacy of diet therapy in managing lipedema.
Once informed consent has been obtained, participants will complete 1 screening visit.

      The screening visit includes a medical history, physical examination, pregnancy test (for
      women of childbearing potential), blood tests, urine drug test, an oral glucose tolerance
      test, resting electrocardiogram (ECG), and questionnaires.

      Baseline testing will be performed in 2 visits requiring 1 inpatient overnight stay and will
      require approximately 30 hours in total to complete testing. Testing will include imaging
      scans to determine thigh fat mass; abdominal (belly) fat mass and liver fat content; DXA scan
      to assess whole-body and leg fat mass; blood samples; hyperinsulinemic-euglycemic clamp
      procedure; immune system function/inflammation (performed exclusively in people with obesity
      and lipedema and BMI-matched controls); and adipose tissue (fat) biopsies.

      Once Baseline Testing is completed, participants will start 5-10% dietitian and/or
      behaviorist guided weight-loss for about 4 to 6 months.

      Participant will keep a food diary and have weekly visits (in person or remote) with a study
      dietitian and/or behaviorist.

      After weight loss, the testing completed during baseline will be repeated.

      Study procedures:

        1. Medical history & physical exam

        2. Urine drug/pregnancy Test

        3. Blood pressure, pulse, height, weight

        4. Electrocardiogram (ECG)

        5. Blood tests for routine lab analyses

        6. Oral glucose tolerance test (OGTT)

        7. Screening Questionnaires

        8. Dual energy X-ray absorptiometry (DXA) scan to assess whole-body and leg fat mass

        9. Magnetic Resonance Imaging (MRI) for Body Composition to determine the amount of fat in
           the liver, abdomen (belly), and thigh.

       10. Metabolism study (hyperinsulinemic-euglycemic clamp procedure) to assess how well
           insulin works to control blood glucose (sugar) concentrations.

       11. Abdominal (belly) and thigh fat biopsies

       12. Immune function (performed in obese with lipedema subjects and BMI-matched controls).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Body Composition and Fat distribution
time frame: 6 months
description: total body, upper and lower body fat masses, ii) intra-abdominal fat, and iii) intrahepatic triglyceride content
measure: Metabolic function insulin sensitivity
time frame: 7 months
description: multi-organ (liver, skeletal muscle and adipose tissue) insulin sensitivity
measure: Metabolic function
time frame: 6 months
description: β-cell function.
measure: Immune system function (obese women with lipedema and BMI-matched controls)
time frame: 6 months
description: upper and lower body subcutaneous adipose tissue stromal vascular fraction content of immune cells; and ii) upper and lower body subcutaneous adipose tissue gene expression of markers of inflammation.
arm group label: Baseline Lipedema characterization
arm group type: Experimental
description: Body composition and Fat distribution, adipose tissue biology, metabolic and immune function in women with Lipedema. Participants will receive a low-calorie diet therapy in the form of low calorie meals or shakes.
intervention type: Dietary Supplement
intervention name: Weight loss
description: Participants will lose weight by utilizing a low caloric diet and meeting with a study dietitian and/or behaviorist weekly for ~4 months.
arm group label: Baseline Lipedema characterization
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 68 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Samuel Klein, MD
role: Principal Investigator
affiliation: Washington University School of Medicine
last name: Johanna Sonnenschein
phone: 314-747-2627
email: j.sonnenschein@wustl.edu
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Lipedema
mesh term: Weight Loss