xml: <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/NCT06003153</url>
    </required_header>
    <id_info>
      <org_study_id>2023P001852</org_study_id>
      <secondary_id>K23DK131345</secondary_id>
      <nct_id>NCT06003153</nct_id>
    </id_info>
    <brief_title>GLUCOSE-MGH: Genetic Links Understood Through Challenge With Oral Semaglutide Exposure at MGH</brief_title>
    <acronym>GLUCOSE-MGH</acronym>
    <official_title>GLUCOSE-MGH: Genetic Links Understood Through Challenge With Oral Semaglutide Exposure at MGH</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Massachusetts General Hospital</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>Massachusetts General Hospital</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of this research study is to evaluate the pathophysiologic mechanisms by which&#xD;
        genetic variation impacts response to an FDA-approved medication commonly used to treat&#xD;
        diabetes and obesity called oral semaglutide (Rybelsus) and to characterize the physiological&#xD;
        response to a mixed meal tolerance test (MMTT) before and after a 14-day treatment with&#xD;
        Rybelsus. The effect of oral semaglutide (Rybelsus) on human beings is similar regardless of&#xD;
        whether the person taking them has diabetes or not. The investigators will do this by&#xD;
        measuring factors in the blood, such as sugars, fats, metabolites, and proteins, after eating&#xD;
        a standardized breakfast meal at the first visit and after taking 14 doses of oral&#xD;
        semaglutide (Rybelsus) over two weeks before the second study visit. The food (mixed meal&#xD;
        breakfast) we will be studying is specially prepared to contain a set amount of protein,&#xD;
        carbohydrates, and fat. The investigators hypothesize that understanding how the acute&#xD;
        biochemical response to oral semaglutide differs by genetic variation will generate insight&#xD;
        into drug mechanisms and Type 2 Diabetes pathophysiology.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 1, 2023</start_date>
    <completion_date type="Anticipated">December 30, 2027</completion_date>
    <primary_completion_date type="Anticipated">December 30, 2027</primary_completion_date>
    <phase>Phase 4</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>Insulin response to oral semaglutide treatment</measure>
      <time_frame>15 days</time_frame>
      <description>Investigators will measure the change in insulin area under the curve (AUC) over 120 minutes of the MMTT, calculated using the trapezoidal method, between Visit 1 and Visit 2 as an index of response to oral semaglutide, and compare this outcome by genotype at selected loci.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Fasting glucose response to oral semaglutide treatment</measure>
      <time_frame>15 days</time_frame>
      <description>Investigators will measure the change in fasting glucose over 120 minutes of the MMTT, between the two visits, and compare this outcome by genotype at selected loci.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cumulative glucose response to oral semaglutide treatment</measure>
      <time_frame>15 days</time_frame>
      <description>Investigators will measure the change in glucose area under the curve (AUC) over 120 minutes of the MMTT, between the two visits, and compare this outcome by genotype at selected loci.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Baseline incretin level</measure>
      <time_frame>120 minutes during Visit 1</time_frame>
      <description>Investigators will measure levels of GLP-1 during the length of the baseline MMTT (120 minutes) that takes place on Visit 1, and compare changes in the baseline levels by genotype at selected loci.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">125</enrollment>
    <condition>Genetic Predisposition</condition>
    <condition>Metabolic Diseases</condition>
    <condition>Type 2 Diabetes</condition>
    <arm_group>
      <arm_group_label>GLUCOSE-MGH Study</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Day 1: Mixed meal tolerance test&#xD;
  Day 3-15: 7mg Rybelsus, once daily&#xD;
  Day 16: 1 dose of 7mg Rybelsus, Mixed meal tolerance test in the presence of Rybelsus</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Mixed Meal Tolerance Test (MMTT)</intervention_name>
      <description>The MMTT meal will provide a standard amount of total calories, protein, fat and carbohydrate to each participant at both study visits. Pre-packaged and freshly prepared food will be given in this MMTT. The participants will undergo a MMTT at Visit 1 and Visit 2.</description>
      <arm_group_label>GLUCOSE-MGH Study</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Rybelsus</intervention_name>
      <description>Rybelsus will be administered during this study. This medication is safely prescribed for the treatment of type 2 diabetes and obesity. We will give 14 doses (7mg each dose) to study participants over 14 days. Another MMTT will be performed after the 14th dose of Rybelsus.</description>
      <arm_group_label>GLUCOSE-MGH Study</arm_group_label>
      <other_name>Oral Semaglutide</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Males or non-pregnant females&#xD;
  &#xD;
            2. Ages 18-50 (inclusive)&#xD;
  &#xD;
            3. Able/willing to give consent&#xD;
  &#xD;
            4. Span the metabolic range between normal glycemia and pre-diabetes (fasting glucose of&#xD;
               100-125 mg/dL based on chart review of existing laboratory data)&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Currently taking medications or intending to take medications for diabetes&#xD;
  &#xD;
            2. Currently taking medications or intending to take medications that affect glycemic&#xD;
               parameters, such as glucocorticoids, growth hormone, or fluoroquinolones&#xD;
  &#xD;
            3. Personal history of intestinal malabsorption, bariatric surgery, celiac disease,&#xD;
               gallbladder disease, or pancreatitis&#xD;
  &#xD;
            4. Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia&#xD;
               type 2&#xD;
  &#xD;
            5. Estimated glomerular filtration rate (eGFR) &lt;60 ml/min/1.73 m2 per the Modification of&#xD;
               Diet in Renal Disease equation&#xD;
  &#xD;
            6. History of cirrhosis and/or aspartate aminotransferase or alanine aminotransferase&#xD;
               more than 3x upper limit of normal&#xD;
  &#xD;
            7. Dietary restrictions preventing consumption of a MMTT&#xD;
  &#xD;
            8. Women who are pregnant, nursing, or at risk of becoming pregnant&#xD;
  &#xD;
            9. Participation in other interventional studies during the current study&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>50 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Josephine Li, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>MGH</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Varinderpal Kaur</last_name>
      <phone>6176435419</phone>
      <email>vkaur@mgh.harvard.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Josephine Li</last_name>
      <phone>617-643-4987</phone>
      <email>jli71@mgh.harvard.edu</email>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 9, 2023</study_first_submitted>
    <study_first_submitted_qc>August 18, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 18, 2023</last_update_submitted>
    <last_update_submitted_qc>August 18, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
      <investigator_full_name>Josephine Li, MD</investigator_full_name>
      <investigator_title>Assistant Professor of Medicine</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Metabolic Diseases</mesh_term>
      <mesh_term>Genetic Predisposition to Disease</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06003153
  org study id: 2023P001852
  secondary id: K23DK131345
  nct id: NCT06003153
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: Yes
  The goal of this research study is to evaluate the pathophysiologic mechanisms by which
        genetic variation impacts response to an FDA-approved medication commonly used to treat
        diabetes and obesity called oral semaglutide (Rybelsus) and to characterize the physiological
        response to a mixed meal tolerance test (MMTT) before and after a 14-day treatment with
        Rybelsus. The effect of oral semaglutide (Rybelsus) on human beings is similar regardless of
        whether the person taking them has diabetes or not. The investigators will do this by
        measuring factors in the blood, such as sugars, fats, metabolites, and proteins, after eating
        a standardized breakfast meal at the first visit and after taking 14 doses of oral
        semaglutide (Rybelsus) over two weeks before the second study visit. The food (mixed meal
        breakfast) we will be studying is specially prepared to contain a set amount of protein,
        carbohydrates, and fat. The investigators hypothesize that understanding how the acute
        biochemical response to oral semaglutide differs by genetic variation will generate insight
        into drug mechanisms and Type 2 Diabetes pathophysiology.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Insulin response to oral semaglutide treatment
  time frame: 15 days
  description: Investigators will measure the change in insulin area under the curve (AUC) over 120 minutes of the MMTT, calculated using the trapezoidal method, between Visit 1 and Visit 2 as an index of response to oral semaglutide, and compare this outcome by genotype at selected loci.
  measure: Fasting glucose response to oral semaglutide treatment
  time frame: 15 days
  description: Investigators will measure the change in fasting glucose over 120 minutes of the MMTT, between the two visits, and compare this outcome by genotype at selected loci.
  measure: Cumulative glucose response to oral semaglutide treatment
  time frame: 15 days
  description: Investigators will measure the change in glucose area under the curve (AUC) over 120 minutes of the MMTT, between the two visits, and compare this outcome by genotype at selected loci.
  measure: Baseline incretin level
  time frame: 120 minutes during Visit 1
  description: Investigators will measure levels of GLP-1 during the length of the baseline MMTT (120 minutes) that takes place on Visit 1, and compare changes in the baseline levels by genotype at selected loci.
  arm group label: GLUCOSE-MGH Study
  arm group type: Other
  description: Day 1: Mixed meal tolerance test
  Day 3-15: 7mg Rybelsus, once daily
  Day 16: 1 dose of 7mg Rybelsus, Mixed meal tolerance test in the presence of Rybelsus
  intervention type: Other
  intervention name: Mixed Meal Tolerance Test (MMTT)
  description: The MMTT meal will provide a standard amount of total calories, protein, fat and carbohydrate to each participant at both study visits. Pre-packaged and freshly prepared food will be given in this MMTT. The participants will undergo a MMTT at Visit 1 and Visit 2.
  arm group label: GLUCOSE-MGH Study
  intervention type: Drug
  intervention name: Rybelsus
  description: Rybelsus will be administered during this study. This medication is safely prescribed for the treatment of type 2 diabetes and obesity. We will give 14 doses (7mg each dose) to study participants over 14 days. Another MMTT will be performed after the 14th dose of Rybelsus.
  arm group label: GLUCOSE-MGH Study
  other name: Oral Semaglutide
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 50 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Josephine Li, MD
  role: Principal Investigator
  affiliation: MGH
  last name: Varinderpal Kaur
  phone: 6176435419
  email: vkaur@mgh.harvard.edu
  last name: Josephine Li
  phone: 617-643-4987
  email: jli71@mgh.harvard.edu
  responsible party type: Principal Investigator
  investigator affiliation: Massachusetts General Hospital
  investigator full name: Josephine Li, MD
  investigator title: Assistant Professor of Medicine
  mesh term: Metabolic Diseases
  mesh term: Genetic Predisposition to Disease