<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/NCT02207777</url>
  </required_header>
  <id_info>
    <org_study_id>201403065</org_study_id>
    <secondary_id>1R01DK101578</secondary_id>
    <nct_id>NCT02207777</nct_id>
  </id_info>
  <brief_title>Weight Loss-Independent Metabolic Effects of Roux-En-Y Gastric Bypass in Diabetes</brief_title>
  <acronym>RBD-T2D</acronym>
  <official_title>Weight Loss-Independent Metabolic Effects of Roux-En-Y Gastric Bypass in Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Washington University School of Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      For this purpose, we will compare the effects of targeted 16-18% (with a range of 16-25%)&#xD;
      weight loss induced by Roux-en-Y Gastric bypass (RYGB) surgery with the same weight loss&#xD;
      induced by a low-calorie diet (LCD) on liver and skeletal muscle insulin sensitivity,&#xD;
      beta-cell function, and 24-hour metabolic homeostasis in obese subjects with or without T2D.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 2014</start_date>
  <completion_date type="Anticipated">April 2025</completion_date>
  <primary_completion_date type="Anticipated">April 2024</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in hepatic insulin sensitivity</measure>
    <time_frame>6 months (before and after targeted weight loss)</time_frame>
    <description>The outcome will be assessed by hyperinsulinemic-euglycemic-pancreatic-clamp procedure before and after weight loss.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in skeletal muscle and adipose tissue insulin sensitivity</measure>
    <time_frame>6 months (before and after targeted weight loss)</time_frame>
    <description>The outcome will be assessed by hyperinsulinemic-euglycemic-pancreatic-clamp procedure before and after weight loss.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Beta-cell function</measure>
    <time_frame>6 months (before and after targeted weight loss)</time_frame>
    <description>The outcome will be assessed as the product of beta-cell glucose sensitivity (ratio of post-meal insulin secretion rate to post-meal plasma glucose) during mixed-meal test and whole-body insulin sensitivity before and after weight loss.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in glucose kinetics (glucose concentration and rate of appearance into the systemic circulation) in response to mixed-meal ingestion</measure>
    <time_frame>6 months (before and after targeted weight loss)</time_frame>
    <description>The outcome will be measured by using dual glucose tracer mixed meal metabolic test and serial blood sampling for 4 hours before and after weight loss</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in 24-hour plasma glucose profile</measure>
    <time_frame>6 months (before and after targeted weight loss)</time_frame>
    <description>The outcome will be determined by obtaining serial plasma glucose concentration measurements for 24 hours before and after weight loss</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in 24-hour plasma insulin profile</measure>
    <time_frame>6 months (before and after targeted weight loss)</time_frame>
    <description>The outcome will determined by obtaining serial plasma insulin concentration measurements for 24 hours before and after weight loss</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in 24-hour plasma free fatty acid profile</measure>
    <time_frame>6 months (before and after targeted weight loss)</time_frame>
    <description>The outcome will determined by obtaining serial plasma free fatty acid concentration measurements for 24 hours before and after weight loss</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in body fat mass</measure>
    <time_frame>6 months (before and after targeted weight loss)</time_frame>
    <description>The outcome will be measured by using dual-energy X-ray absorptiometry before and after weight loss</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in intra-abdominal adipose tissue volume</measure>
    <time_frame>6 months (before and after targeted weight loss)</time_frame>
    <description>The outcome will be measured by using magnetic resonance imaging before and after weight loss</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in intrahepatic triglyceride content</measure>
    <time_frame>6 months (before and after targeted weight loss)</time_frame>
    <description>The outcome will be measured by using magnetic resonance imaging before and after weight loss</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in fat free mass</measure>
    <time_frame>6 months (before and after targeted weight loss)</time_frame>
    <description>The outcome will be measured by using dual-energy X-ray absorptiometry before and after weight loss</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">70</enrollment>
  <condition>Obesity</condition>
  <condition>Type 2 Diabetes</condition>
  <arm_group>
    <arm_group_label>Roux-en-Y gastric bypass (RYGB)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects in this group are scheduled to undergo roux-en-Y gastric bypass surgery to obtain approximately 16-18% (with a range of 16-25%) weight loss.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low-calorie diet</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects in this group will participate in a low-calorie diet intervention to obtain approximately 16-18% (with a range of 16-25%) weight loss.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Roux-en-Y gastric bypass surgery</intervention_name>
    <description>A surgical procedure to help subjects lose approximately 16-18% (with a range of 16-25%) of their body weight.</description>
    <arm_group_label>Roux-en-Y gastric bypass (RYGB)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Low-calorie diet</intervention_name>
    <description>Subjects will meet with a dietitian and/or behaviorist over approximately 6 months to lose approximately 16-18% (with a range of 16-25%) of their body weight.</description>
    <arm_group_label>Low-calorie diet</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        For RYGB group:&#xD;
&#xD;
          -  Scheduled for this bariatric surgery&#xD;
&#xD;
          -  Body Mass Index (BMI) 34-55 kg/m²&#xD;
&#xD;
          -  Type 2 Diabetes&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        For Low-Calorie Diet group:&#xD;
&#xD;
          -  BMI 34-55 kg/m²&#xD;
&#xD;
          -  Type 2 Diabetes and Non-Diabetics&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        For both RYGB &amp; Low-Calorie Diet groups&#xD;
&#xD;
          -  Regular use of tobacco products&#xD;
&#xD;
          -  Previous intestinal resection&#xD;
&#xD;
          -  Pregnant or breastfeeding&#xD;
&#xD;
          -  Evidence of significant organ system dysfunction or disease other than T2D&#xD;
&#xD;
          -  Use of any medication that might, in the opinion of the investigator, affect metabolic&#xD;
             function&#xD;
&#xD;
          -  Exercise ≥90 minutes per week&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</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>
  <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>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Yoshino M, Kayser BD, Yoshino J, Stein RI, Reeds D, Eagon JC, Eckhouse SR, Watrous JD, Jain M, Knight R, Schechtman K, Patterson BW, Klein S. Effects of Diet versus Gastric Bypass on Metabolic Function in Diabetes. N Engl J Med. 2020 Aug 20;383(8):721-732. doi: 10.1056/NEJMoa2003697.</citation>
    <PMID>32813948</PMID>
  </results_reference>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>July 31, 2014</study_first_submitted>
  <study_first_submitted_qc>July 31, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 4, 2014</study_first_posted>
  <last_update_submitted>April 21, 2023</last_update_submitted>
  <last_update_submitted_qc>April 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Obesity</keyword>
  <keyword>Roux-en-Y gastric bypass (RYGB)</keyword>
  <keyword>Type 2 Diabetes</keyword>
  <keyword>Weight Loss</keyword>
  <keyword>Low-Calorie Diet</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</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/NCT02207777
org study id: 201403065
secondary id: 1R01DK101578
nct id: NCT02207777
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
For this purpose, we will compare the effects of targeted 16-18% (with a range of 16-25%)
      weight loss induced by Roux-en-Y Gastric bypass (RYGB) surgery with the same weight loss
      induced by a low-calorie diet (LCD) on liver and skeletal muscle insulin sensitivity,
      beta-cell function, and 24-hour metabolic homeostasis in obese subjects with or without T2D.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Changes in hepatic insulin sensitivity
time frame: 6 months (before and after targeted weight loss)
description: The outcome will be assessed by hyperinsulinemic-euglycemic-pancreatic-clamp procedure before and after weight loss.
measure: Changes in skeletal muscle and adipose tissue insulin sensitivity
time frame: 6 months (before and after targeted weight loss)
description: The outcome will be assessed by hyperinsulinemic-euglycemic-pancreatic-clamp procedure before and after weight loss.
measure: Changes in Beta-cell function
time frame: 6 months (before and after targeted weight loss)
description: The outcome will be assessed as the product of beta-cell glucose sensitivity (ratio of post-meal insulin secretion rate to post-meal plasma glucose) during mixed-meal test and whole-body insulin sensitivity before and after weight loss.
measure: Changes in glucose kinetics (glucose concentration and rate of appearance into the systemic circulation) in response to mixed-meal ingestion
time frame: 6 months (before and after targeted weight loss)
description: The outcome will be measured by using dual glucose tracer mixed meal metabolic test and serial blood sampling for 4 hours before and after weight loss
measure: Changes in 24-hour plasma glucose profile
time frame: 6 months (before and after targeted weight loss)
description: The outcome will be determined by obtaining serial plasma glucose concentration measurements for 24 hours before and after weight loss
measure: Changes in 24-hour plasma insulin profile
time frame: 6 months (before and after targeted weight loss)
description: The outcome will determined by obtaining serial plasma insulin concentration measurements for 24 hours before and after weight loss
measure: Changes in 24-hour plasma free fatty acid profile
time frame: 6 months (before and after targeted weight loss)
description: The outcome will determined by obtaining serial plasma free fatty acid concentration measurements for 24 hours before and after weight loss
measure: Changes in body fat mass
time frame: 6 months (before and after targeted weight loss)
description: The outcome will be measured by using dual-energy X-ray absorptiometry before and after weight loss
measure: Changes in intra-abdominal adipose tissue volume
time frame: 6 months (before and after targeted weight loss)
description: The outcome will be measured by using magnetic resonance imaging before and after weight loss
measure: Changes in intrahepatic triglyceride content
time frame: 6 months (before and after targeted weight loss)
description: The outcome will be measured by using magnetic resonance imaging before and after weight loss
measure: Changes in fat free mass
time frame: 6 months (before and after targeted weight loss)
description: The outcome will be measured by using dual-energy X-ray absorptiometry before and after weight loss
arm group label: Roux-en-Y gastric bypass (RYGB)
arm group type: Experimental
description: Subjects in this group are scheduled to undergo roux-en-Y gastric bypass surgery to obtain approximately 16-18% (with a range of 16-25%) weight loss.
arm group label: Low-calorie diet
arm group type: Active Comparator
description: Subjects in this group will participate in a low-calorie diet intervention to obtain approximately 16-18% (with a range of 16-25%) weight loss.
intervention type: Procedure
intervention name: Roux-en-Y gastric bypass surgery
description: A surgical procedure to help subjects lose approximately 16-18% (with a range of 16-25%) of their body weight.
arm group label: Roux-en-Y gastric bypass (RYGB)
intervention type: Behavioral
intervention name: Low-calorie diet
description: Subjects will meet with a dietitian and/or behaviorist over approximately 6 months to lose approximately 16-18% (with a range of 16-25%) of their body weight.
arm group label: Low-calorie diet
criteria: 
gender: All
minimum age: 25 Years
maximum age: 65 Years
healthy volunteers: No
last name: Samuel Klein, MD
role: Principal Investigator
affiliation: Washington University School of Medicine
facility: 
country: United States
citation: Yoshino M, Kayser BD, Yoshino J, Stein RI, Reeds D, Eagon JC, Eckhouse SR, Watrous JD, Jain M, Knight R, Schechtman K, Patterson BW, Klein S. Effects of Diet versus Gastric Bypass on Metabolic Function in Diabetes. N Engl J Med. 2020 Aug 20;383(8):721-732. doi: 10.1056/NEJMoa2003697.
PMID: 32813948
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Weight Loss