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/NCT06005012</url>
    </required_header>
    <id_info>
      <org_study_id>NRC-2023-1</org_study_id>
      <nct_id>NCT06005012</nct_id>
    </id_info>
    <brief_title>Semaglutide Treatment in the Real-world for Fibrosis Due to NAFLD in Obesity and T2DM</brief_title>
    <acronym>SAMARA</acronym>
    <official_title>Semaglutide Treatment in the Real-world for Fibrosis Due to NAFLD in Obesity and T2DM</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of California, San Diego</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of California, San Diego</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>
    </oversight_info>
    <brief_summary>
      <textblock>
        Conduct a community intervention study that will 1) validate a screening approach to identify&#xD;
        patients at risk for advanced NAFLD in the obese or T2DM population, and 2) test whether&#xD;
        semaglutide treatment is effective for the management of significant fibrosis due to NAFLD in&#xD;
        high-risk patients.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Nonalcoholic fatty liver disease (NAFLD) affects approximately 25-30% of the global&#xD;
        population and is projected to become the leading cause of liver transplantation in the&#xD;
        United States by 2030. Development of efficient screening strategies for the identification&#xD;
        and treatment of individuals who are at greatest risk for advanced disease in this population&#xD;
        is an urgent and unmet medical need. Type 2 diabetes mellitus (T2DM) and obesity are critical&#xD;
        risk factors for advanced NAFLD. In a prospective cross-sectional study of patients with type&#xD;
        2 diabetes, we screened 524 participants (50-80 years old) with type 2 diabetes mellitus for&#xD;
        the presence of NAFLD and observed relative prevalences of 70% for steatosis and 15% for&#xD;
        advanced fibrosis. The presence of obesity in this population further increased the odds of&#xD;
        advanced fibrosis. These findings suggest that screening populations of individuals with&#xD;
        obesity or T2DM may be an effective strategy for identifying high-risk patients with NAFLD.&#xD;
        Semaglutide is a glucagon-like peptide 1 receptor agonist (GLP-1 RA) that is FDA-approved for&#xD;
        the treatment of obesity (as Wegovy) or T2DM (as Ozempic), conditions that are considered&#xD;
        major risk factors for advanced fibrosis in the NAFLD population. It is unclear, however,&#xD;
        whether semaglutide is effective for treatment of fibrosis due to NAFLD in these populations.&#xD;
        Here, the investigators propose to conduct a community intervention study that will 1)&#xD;
        validate a screening approach to identify patients at risk for advanced NAFLD in the obese or&#xD;
        T2DM population, and 2) test whether semaglutide treatment is effective for the management of&#xD;
        significant fibrosis due to NAFLD in high-risk patients.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 25, 2023</start_date>
    <completion_date type="Anticipated">June 2025</completion_date>
    <primary_completion_date type="Anticipated">March 2025</primary_completion_date>
    <phase>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>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Triple (Participant, Care Provider, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Change in fibrosis due to NAFLD</measure>
      <time_frame>52 weeks</time_frame>
      <description>Change in fibrosis due to Nonalcoholic fatty liver disease (NAFLD), as measured by change in FAST Score, which combines FibroScan results with aspartate aminotransferase (AST).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change in liver stiffness</measure>
      <time_frame>52 weeks</time_frame>
      <description>Change in liver stiffness, as measured by change in Vibration-Controlled Transient Elastography</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in steatosis</measure>
      <time_frame>52 weeks</time_frame>
      <description>Change in steatosis, as measure by a change in proton density fat fraction or controlled attenuation parameter</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in ALT</measure>
      <time_frame>52 weeks</time_frame>
      <description>Change in ALT, as measured by a change in patients with ALT &gt;= 30 U/L at baseline</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">120</enrollment>
    <condition>Fibrosis, Liver</condition>
    <condition>Type 2 Diabetes Mellitus in Obese</condition>
    <condition>Non-Alcoholic Fatty Liver Disease</condition>
    <arm_group>
      <arm_group_label>Semaglutide</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>2.4 mg weekly for 52 weekly in a 3 ml PDS290 pen-injector containing Semaglutide 3.0 mg/ml for subcutaneous use</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>2.4 mg weekly for 52 weekly in a 3 ml PDS290 pen-injector containing 3.0 mg/ml of a placebo solution for subcutaneous use</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Semaglutide</intervention_name>
      <description>Semaglutide is a glucagon-like peptide 1 receptor agonist (GLP-1 RA) that is FDA-approved for the treatment of obesity (as Wegovy) or T2DM (as Ozempic).</description>
      <arm_group_label>Semaglutide</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Placebo</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion criteria:&#xD;
  &#xD;
            1. Adult, age ≥ 40 and &lt; 80 years&#xD;
  &#xD;
            2. Participant must meet at least one of following sets of conditions:&#xD;
  &#xD;
                 1. BMI ≥ 27 kg/m² OR&#xD;
  &#xD;
                 2. BMI ≥ 25 kg/m² AND presence of i) pre-diabetes (HbA1C ≥ 5.7) or ii) type 2&#xD;
                    diabetes mellitus (T2DM), as defined by the American Diabetes Association (ADA)&#xD;
                    clinical practice recommendations.&#xD;
  &#xD;
               The ADA definition of T2DM is applicable if one of the following criteria is met:&#xD;
  &#xD;
                 -  Presence of diabetes symptoms (polyuria, polydipsia, polyphagia, increased&#xD;
                    fatigue, weight loss, blurred vision) and casual plasma glucose ≥ 200 mg/dL (11.1&#xD;
                    mmol/L)&#xD;
  &#xD;
                 -  Fasting plasma glucose (FPG) ≥ 126 mg/dl (7.0 mmol/L)&#xD;
  &#xD;
                 -  Plasma glucose ≥ 200 mg/dL (11.1 mmol/L) during a 75-g oral glucose tolerance&#xD;
                    test (OGTT)⁶⁸. If any of the above test results occur, testing should be repeated&#xD;
                    on a different day to confirm the diagnosis.&#xD;
  &#xD;
               OR&#xD;
  &#xD;
               • Hemoglobin A1C (HbA1C) ≥ 6.5% ⁶⁹.&#xD;
  &#xD;
            3. FAST score ≥ 0.5 and VCTE ≥ 8.0 kPa; FAST score threshold based on data from&#xD;
               MAESTRO-NASH trial⁴²; VCTE cutpoint based on AASLD guidelines for identification of&#xD;
               patients with significant fibrosis risk.&#xD;
  &#xD;
            4. Participants without a VCTE assessment in their medical record may qualify for the&#xD;
               study if they have a FIB-4 ≥ 1.0, which is a cutpoint based on observations of&#xD;
               patients with T2DM in Ajmera et al³⁰, and VCTE ≥ 8.0 kPa.&#xD;
  &#xD;
            5. The subject is fully informed and willing and able to perform all the procedures&#xD;
               specified in the protocol and has signed a written informed consent to participate&#xD;
  &#xD;
          Exclusion criteria:&#xD;
  &#xD;
            1. Presence of regular and/or excessive use of alcohol, defined as &gt; 30 g/day for males&#xD;
               and &gt; 20 g/day for females, for a period longer than 2 years at any time in the last&#xD;
               10 years&#xD;
  &#xD;
            2. Evidence of cirrhosis or previously known cirrhosis, based on the results from&#xD;
               previous liver biopsy or history of portal hypertension presented by ascites, hepatic&#xD;
               encephalopathy or varices&#xD;
  &#xD;
            3. VCTE ≥ 20 kPa&#xD;
  &#xD;
            4. Platelet count ≤ 140,000 per Ml&#xD;
  &#xD;
            5. Albumin &lt; 3.6 g/dL&#xD;
  &#xD;
            6. INR &gt; 1.35, unless on coumadin for another indication&#xD;
  &#xD;
            7. Serum creatinine &gt; 2.0 mg/dL&#xD;
  &#xD;
            8. eGFR &lt; 30 mL/min/1.73 m² as defined according to the CKDEPI creatinine equation⁷⁰&#xD;
  &#xD;
            9. Use of other weight loss medications, including GLP1RA within the last 90 days&#xD;
  &#xD;
           10. Greater than 10% weight loss in the prior six months&#xD;
  &#xD;
           11. Known or suspected hypersensitivity to GLP1RA medications including semaglutide&#xD;
  &#xD;
           12. History of bariatric surgery within the past 5 years or expected bariatric surgery&#xD;
  &#xD;
           13. Evidence of other causes of chronic liver disease including:&#xD;
  &#xD;
                 1. Hepatitis B, as defined as presence of hepatitis B surface antigen (HBsAg).&#xD;
  &#xD;
                 2. Previous or current infection with Hepatitis C, as defined by presence of&#xD;
                    hepatitis C virus Ab in serum (anti-HCV Ab).&#xD;
  &#xD;
                 3. Autoimmune hepatitis, as defined by anti-nuclear antibody (ANA) of 1:160 or&#xD;
                    greater and liver histology consistent with autoimmune hepatitis or previous&#xD;
                    response to immunosuppressive therapy.&#xD;
  &#xD;
                 4. Autoimmune cholestatic liver disorders, as defined by elevation of alkaline&#xD;
                    phosphatase and anti- mitochondrial antibody of greater than 1:80 or liver&#xD;
                    histology consistent with primary biliary cirrhosis or elevation of alkaline&#xD;
                    phosphatase and liver histology consistent with sclerosing cholangitis.&#xD;
  &#xD;
                 5. Wilson disease, as defined by ceruloplasmin below the limits of normal and liver&#xD;
                    histology consistent with Wilson disease deficiency, as defined by&#xD;
                    alpha-1-antitrypsin phenotype and liver histology consistent with&#xD;
                    alpha-1-antitrypsin deficiency.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>40 Years</minimum_age>
      <maximum_age>79 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Rohit Loomba</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of California, San Diego</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Egbert Madamba</last_name>
      <phone>(858) 246-2227</phone>
      <email>emadamba@health.ucsd.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>University of California, San Diego</name>
        <address>
          <city>La Jolla</city>
          <state>California</state>
          <zip>92093</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Egbert Madamba</last_name>
        <phone>858-246-2227</phone>
        <email>emadamba@health.ucsd.edu</email>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 16, 2023</study_first_submitted>
    <study_first_submitted_qc>August 16, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 22, 2023</study_first_posted>
    <last_update_submitted>September 1, 2023</last_update_submitted>
    <last_update_submitted_qc>September 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 7, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of California, San Diego</investigator_affiliation>
      <investigator_full_name>Rohit Loomba</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Liver Diseases</mesh_term>
      <mesh_term>Fatty Liver</mesh_term>
      <mesh_term>Non-alcoholic Fatty Liver Disease</mesh_term>
      <mesh_term>Liver Cirrhosis</mesh_term>
      <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
      <mesh_term>Fibrosis</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/NCT06005012
  org study id: NRC-2023-1
  nct id: NCT06005012
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  Conduct a community intervention study that will 1) validate a screening approach to identify
        patients at risk for advanced NAFLD in the obese or T2DM population, and 2) test whether
        semaglutide treatment is effective for the management of significant fibrosis due to NAFLD in
        high-risk patients.
  Nonalcoholic fatty liver disease (NAFLD) affects approximately 25-30% of the global
        population and is projected to become the leading cause of liver transplantation in the
        United States by 2030. Development of efficient screening strategies for the identification
        and treatment of individuals who are at greatest risk for advanced disease in this population
        is an urgent and unmet medical need. Type 2 diabetes mellitus (T2DM) and obesity are critical
        risk factors for advanced NAFLD. In a prospective cross-sectional study of patients with type
        2 diabetes, we screened 524 participants (50-80 years old) with type 2 diabetes mellitus for
        the presence of NAFLD and observed relative prevalences of 70% for steatosis and 15% for
        advanced fibrosis. The presence of obesity in this population further increased the odds of
        advanced fibrosis. These findings suggest that screening populations of individuals with
        obesity or T2DM may be an effective strategy for identifying high-risk patients with NAFLD.
        Semaglutide is a glucagon-like peptide 1 receptor agonist (GLP-1 RA) that is FDA-approved for
        the treatment of obesity (as Wegovy) or T2DM (as Ozempic), conditions that are considered
        major risk factors for advanced fibrosis in the NAFLD population. It is unclear, however,
        whether semaglutide is effective for treatment of fibrosis due to NAFLD in these populations.
        Here, the investigators propose to conduct a community intervention study that will 1)
        validate a screening approach to identify patients at risk for advanced NAFLD in the obese or
        T2DM population, and 2) test whether semaglutide treatment is effective for the management of
        significant fibrosis due to NAFLD in high-risk patients.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Triple (Participant, Care Provider, Investigator)
  measure: Change in fibrosis due to NAFLD
  time frame: 52 weeks
  description: Change in fibrosis due to Nonalcoholic fatty liver disease (NAFLD), as measured by change in FAST Score, which combines FibroScan results with aspartate aminotransferase (AST).
  measure: Change in liver stiffness
  time frame: 52 weeks
  description: Change in liver stiffness, as measured by change in Vibration-Controlled Transient Elastography
  measure: Change in steatosis
  time frame: 52 weeks
  description: Change in steatosis, as measure by a change in proton density fat fraction or controlled attenuation parameter
  measure: Change in ALT
  time frame: 52 weeks
  description: Change in ALT, as measured by a change in patients with ALT >= 30 U/L at baseline
  arm group label: Semaglutide
  arm group type: Experimental
  description: 2.4 mg weekly for 52 weekly in a 3 ml PDS290 pen-injector containing Semaglutide 3.0 mg/ml for subcutaneous use
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: 2.4 mg weekly for 52 weekly in a 3 ml PDS290 pen-injector containing 3.0 mg/ml of a placebo solution for subcutaneous use
  intervention type: Drug
  intervention name: Semaglutide
  description: Semaglutide is a glucagon-like peptide 1 receptor agonist (GLP-1 RA) that is FDA-approved for the treatment of obesity (as Wegovy) or T2DM (as Ozempic).
  arm group label: Semaglutide
  intervention type: Drug
  intervention name: Placebo
  description: Placebo
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 40 Years
  maximum age: 79 Years
  healthy volunteers: No
  last name: Rohit Loomba
  role: Principal Investigator
  affiliation: University of California, San Diego
  last name: Egbert Madamba
  phone: (858) 246-2227
  email: emadamba@health.ucsd.edu
  facility: 
  status: Recruiting
  contact: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: University of California, San Diego
  investigator full name: Rohit Loomba
  investigator title: Professor
  mesh term: Liver Diseases
  mesh term: Fatty Liver
  mesh term: Non-alcoholic Fatty Liver Disease
  mesh term: Liver Cirrhosis
  mesh term: Diabetes Mellitus, Type 2
  mesh term: Fibrosis