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/NCT05972564</url>
    </required_header>
    <id_info>
      <org_study_id>210907 (SADIE2)</org_study_id>
      <nct_id>NCT05972564</nct_id>
    </id_info>
    <brief_title>The Effect of SGLT2 Inhibition on Adipose Inflammation and Endothelial Function</brief_title>
    <acronym>SADIE2</acronym>
    <official_title>The Effect of SGLT2 Inhibition on Adipose Inflammation and Endothelial Function</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Vanderbilt University Medical Center</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Vanderbilt University Medical Center</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>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        Obesity is associated with increased cardiometabolic disease risk due, in part, to heightened&#xD;
        chronic inflammation arising from adipose tissue. There are no current targeted therapies to&#xD;
        prevent or reverse the chronic inflammation of obesity, and a better understanding of these&#xD;
        inflammatory pathways in humans is key to future therapeutic interventions. This trial will&#xD;
        determine both the anti-inflammatory potential of the SGLT2 inhibitor empagliflozin, and the&#xD;
        contribution of adipose inflammation to surrogate measures of cardiovascular disease in a&#xD;
        randomized controlled trial of obese patients.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 30, 2023</start_date>
    <completion_date type="Anticipated">December 30, 2026</completion_date>
    <primary_completion_date type="Anticipated">September 30, 2026</primary_completion_date>
    <phase>Phase 1/Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>Participants will be randomized to placebo or empagliflozin in a 1:1 ratio, stratified for race and sex. A study biostatistician will prepare the randomization and allocation schedule.</intervention_model_description>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
      <masking_description>Placebo consists of gelatin capsules. To ensure blinding, empagliflozin will be over-encapsulated in identical gelatin capsules as placebo.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Adipose tissue macrophages</measure>
      <time_frame>12 weeks</time_frame>
      <description>Homeostatic adipose tissue macrophages are quantified</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Flow mediated dilation</measure>
      <time_frame>12 weeks</time_frame>
      <description>Brachial artery diameter is measured under basal conditions and during reactive hyperemia</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Monocyte chemoattractant protein-1</measure>
      <time_frame>12 weeks</time_frame>
      <description>Plasma monocyte chemoattractant protein-1 levels are quantified</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Pro-inflammatory T cells</measure>
      <time_frame>12 weeks</time_frame>
      <description>Pro-inflammatory T cells are quantified</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>IL-6</measure>
      <time_frame>12 weeks</time_frame>
      <description>Plasma IL-6 levels are quantified</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">74</enrollment>
    <condition>Obesity</condition>
    <condition>Metabolic Syndrome</condition>
    <arm_group>
      <arm_group_label>Empagliflozin Arm</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Empagliflozin is an FDA-approved SGLT2 inhibitor used for the treatment of type 2 diabetes, with off-label use for diabetic kidney disease and for heart failure with reduced ejection fraction even in those without diabetes. To ensure blinding, empagliflozin will be over-encapsulated in identical gelatin capsules as placebo.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo Arm</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Placebo consists of gelatin capsules.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Empagliflozin 25 MG</intervention_name>
      <description>Empagliflozin is an FDA-approved SGLT2 inhibitor used for the treatment of type 2 diabetes, with off-label use for diabetic kidney disease and for heart failure with reduced ejection fraction even in those without diabetes.</description>
      <arm_group_label>Empagliflozin Arm</arm_group_label>
      <other_name>Jardiance</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Placebo consists of gelatin capsules.</description>
      <arm_group_label>Placebo Arm</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age 18 to 70 years old&#xD;
  &#xD;
            2. Metabolic syndrome as defined by 3 or more of 5 criteria:&#xD;
  &#xD;
                 1. Systolic blood pressure ≥ 130 mmHg or diastolic blood pressure ≥ 85 mmg Hg or&#xD;
                    treatment with anti-hypertensive medications for minimum of 6 months&#xD;
  &#xD;
                 2. Triglycerides ≥ 150 mg/dL or treatment with a triglyceride-targeted medication&#xD;
                    (fenofibrate, gemfibrozil, niacin, high dose omega-3 fatty acids)&#xD;
  &#xD;
                 3. High-density lipoprotein (HDL) &lt; 40 mg/dL in males or &lt; 50 mg/dL in females&#xD;
  &#xD;
                 4. Fasting blood glucose ≥ 100mg/dL or treatment with glucose-lowering medications&#xD;
  &#xD;
                 5. Waist circumference ≥ 102 cm in males or ≥ 88cm in females&#xD;
  &#xD;
            3. BMI ≥ 35 kg/M2&#xD;
  &#xD;
            4. Scheduled gastric bypass or gastric sleeve in approximately 90 days (range 90-150&#xD;
               days)&#xD;
  &#xD;
            5. The ability to provide informed consent&#xD;
  &#xD;
               Exclusion Criteria:&#xD;
  &#xD;
            6. Type 1 diabetes.&#xD;
  &#xD;
            7. Poorly controlled type 2 diabetes as defined by HbA1c ≥ 9%.&#xD;
  &#xD;
            8. Use of anti-diabetic medications other than stable dose of metformin or a sulfonylurea&#xD;
               in the last 1 month.&#xD;
  &#xD;
            9. Treatment with a glucagon-like peptide-1 receptor agonist or co-agonist in the last 3&#xD;
               months.&#xD;
  &#xD;
           10. Treatment with an SGLT2 inhibitor in the last 3 months.&#xD;
  &#xD;
           11. Pregnancy or breast-feeding. Women of child-bearing potential will be required to have&#xD;
               undergone surgical sterilization or to be using an intra-uterine device, hormonal&#xD;
               contraceptive, or barrier methods of birth control.&#xD;
  &#xD;
           12. Cardiovascular disease such as myocardial infarction within six months prior to&#xD;
               enrollment, presence of angina pectoris, significant arrhythmia, congestive heart&#xD;
               failure (left ventricular hypertrophy acceptable), deep vein thrombosis, pulmonary&#xD;
               embolism, -second- or third-degree heart block, mitral valve stenosis, aortic&#xD;
               stenosis, or hypertrophic cardiomyopathy&#xD;
  &#xD;
           13. Presence of implanted cardiac defibrillator or pacemaker&#xD;
  &#xD;
           14. History of serious neurologic disease such as cerebral hemorrhage, stroke, or&#xD;
               transient ischemic attack&#xD;
  &#xD;
           15. History of pancreatitis or pancreatic surgery&#xD;
  &#xD;
           16. History or presence of immunological or hematological disorders&#xD;
  &#xD;
           17. Clinically significant gastrointestinal impairment that could interfere with drug&#xD;
               absorption&#xD;
  &#xD;
           18. History of advanced liver disease with cirrhosis&#xD;
  &#xD;
           19. Individuals with an eGFR&lt;45 mL/min/1.73 m2, where eGFR is determined by the&#xD;
               four-variable Modification of Diet in Renal Disease (MDRD) equation, where serum&#xD;
               creatinine is expressed in mg/dL and age in years: eGFR (mL/min/1.73m2)=186 •&#xD;
               Scr-1.154 • age-0.203 • (0.742 if female)&#xD;
  &#xD;
           20. Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days&#xD;
               in 1 month)&#xD;
  &#xD;
           21. Treatment with anticoagulants&#xD;
  &#xD;
           22. Any underlying or acute disease requiring regular medication which could possibly pose&#xD;
               a threat to the subject or make implementation of the protocol or interpretation of&#xD;
               the study results difficult&#xD;
  &#xD;
           23. History of alcohol abuse (&gt;14 per week for men and &gt;7 per week for women) or illicit&#xD;
               drug use&#xD;
  &#xD;
           24. Treatment with any investigational drug in the one month preceding the study&#xD;
  &#xD;
           25. Previous randomization in this trial&#xD;
  &#xD;
           26. Mental conditions rendering a subject unable to understand the nature, scope and&#xD;
               possible consequences of the study&#xD;
  &#xD;
           27. Inability to comply with the protocol in the opinion of the principal investigator,&#xD;
               e.g., uncooperative attitude, inability to return for follow-up visits, and&#xD;
               unlikelihood of completing the study&#xD;
  &#xD;
               Criteria Related to Known Adverse Effects of Drug:&#xD;
  &#xD;
           28. Uncircumcised men or men with history of balanitis&#xD;
  &#xD;
           29. History of urinary incontinence&#xD;
  &#xD;
           30. History of recurrent (&gt;3) episodes of vulvovaginitis per year, or severe symptoms&#xD;
  &#xD;
           31. History of Fournier's gangrene&#xD;
  &#xD;
           32. History of recurrent (≥3) UTIs per year or pyelonephritis&#xD;
  &#xD;
           33. History of symptomatic hypotension or conditions predisposing to volume depletion&#xD;
  &#xD;
           34. Known peripheral vascular disease, neuropathy, history of foot ulcers or lower limb&#xD;
               amputations&#xD;
  &#xD;
           35. Treatment with loop diuretics furosemide, torsemide, bumetanide, ethacrynic acid&#xD;
  &#xD;
           36. Known or suspected allergy to trial medications, excipients, or related products&#xD;
  &#xD;
           37. Contraindications to study medications, worded specifically as stated in the product's&#xD;
               prescribing information&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>70 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Monda Mashayekhi, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Vanderbilt University Medical Center</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Mona Mashayekhi, MD</last_name>
      <phone>615-208-5037</phone>
      <email>mona.mashayekhi@vumc.org</email>
    </overall_contact>
    <location>
      <facility>
        <name>Vanderbilt University Medical Center</name>
        <address>
          <city>Nashville</city>
          <state>Tennessee</state>
          <zip>37232</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Mona Mashayekhi, MD</last_name>
        <phone>615-875-6336</phone>
        <email>mona.mashayekhi@vumc.org</email>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 24, 2023</study_first_submitted>
    <study_first_submitted_qc>July 24, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 2, 2023</study_first_posted>
    <last_update_submitted>July 24, 2023</last_update_submitted>
    <last_update_submitted_qc>July 24, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 2, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Vanderbilt University Medical Center</investigator_affiliation>
      <investigator_full_name>Mona Mashayekhi</investigator_full_name>
      <investigator_title>Clinical Instructor, Division of Diabetes, Endocrinology and Metabolism</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Metabolic Syndrome</mesh_term>
      <mesh_term>Inflammation</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Empagliflozin</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>No plan to share IPD outside of VUMC study team.</ipd_description>
    </patient_data>
    <!-- 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/NCT05972564
  org study id: 210907 (SADIE2)
  nct id: NCT05972564
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: No
  Obesity is associated with increased cardiometabolic disease risk due, in part, to heightened
        chronic inflammation arising from adipose tissue. There are no current targeted therapies to
        prevent or reverse the chronic inflammation of obesity, and a better understanding of these
        inflammatory pathways in humans is key to future therapeutic interventions. This trial will
        determine both the anti-inflammatory potential of the SGLT2 inhibitor empagliflozin, and the
        contribution of adipose inflammation to surrogate measures of cardiovascular disease in a
        randomized controlled trial of obese patients.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Participants will be randomized to placebo or empagliflozin in a 1:1 ratio, stratified for race and sex. A study biostatistician will prepare the randomization and allocation schedule.
  primary purpose: Basic Science
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  masking description: Placebo consists of gelatin capsules. To ensure blinding, empagliflozin will be over-encapsulated in identical gelatin capsules as placebo.
  measure: Adipose tissue macrophages
  time frame: 12 weeks
  description: Homeostatic adipose tissue macrophages are quantified
  measure: Flow mediated dilation
  time frame: 12 weeks
  description: Brachial artery diameter is measured under basal conditions and during reactive hyperemia
  measure: Monocyte chemoattractant protein-1
  time frame: 12 weeks
  description: Plasma monocyte chemoattractant protein-1 levels are quantified
  measure: Pro-inflammatory T cells
  time frame: 12 weeks
  description: Pro-inflammatory T cells are quantified
  measure: IL-6
  time frame: 12 weeks
  description: Plasma IL-6 levels are quantified
  arm group label: Empagliflozin Arm
  arm group type: Active Comparator
  description: Empagliflozin is an FDA-approved SGLT2 inhibitor used for the treatment of type 2 diabetes, with off-label use for diabetic kidney disease and for heart failure with reduced ejection fraction even in those without diabetes. To ensure blinding, empagliflozin will be over-encapsulated in identical gelatin capsules as placebo.
  arm group label: Placebo Arm
  arm group type: Placebo Comparator
  description: Placebo consists of gelatin capsules.
  intervention type: Drug
  intervention name: Empagliflozin 25 MG
  description: Empagliflozin is an FDA-approved SGLT2 inhibitor used for the treatment of type 2 diabetes, with off-label use for diabetic kidney disease and for heart failure with reduced ejection fraction even in those without diabetes.
  arm group label: Empagliflozin Arm
  other name: Jardiance
  intervention type: Drug
  intervention name: Placebo
  description: Placebo consists of gelatin capsules.
  arm group label: Placebo Arm
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 70 Years
  healthy volunteers: No
  last name: Monda Mashayekhi, MD
  role: Principal Investigator
  affiliation: Vanderbilt University Medical Center
  last name: Mona Mashayekhi, MD
  phone: 615-208-5037
  email: mona.mashayekhi@vumc.org
  facility: 
  contact: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: Vanderbilt University Medical Center
  investigator full name: Mona Mashayekhi
  investigator title: Clinical Instructor, Division of Diabetes, Endocrinology and Metabolism
  mesh term: Metabolic Syndrome
  mesh term: Inflammation
  mesh term: Empagliflozin
  sharing ipd: No
  ipd description: No plan to share IPD outside of VUMC study team.