<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/NCT03042767</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00084686</org_study_id>
    <nct_id>NCT03042767</nct_id>
  </id_info>
  <brief_title>Anti-LPS Antibody Treatment for Pediatric NAFLD</brief_title>
  <official_title>Anti-LPS Antibody in Pediatric Nonalcoholic Fatty Liver Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Miriam Vos, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Advanced MR Analytics AB</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Immuron Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Emory University</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>
      The main objective of this pilot study is to evaluate whether 12 weeks of IMM-124E in&#xD;
      children with nonalcoholic fatty liver disease (NAFLD) in combination with standard of care&#xD;
      treatment will decrease inflammation in the liver as measured by alanine transaminase (ALT).&#xD;
      Specifically, investigators will measure percent change in ALT from Week 0 to Week 12 in&#xD;
      treatment compared to placebo.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, double blind, placebo controlled, three month treatment trial of&#xD;
      children aged 6-19 years. Participants will be recruited from the Children's Healthcare of&#xD;
      Atlanta pediatric liver clinical practice.The purpose of this study is to evaluate if a three&#xD;
      month treatment with IMM-124E (a bovine colostrum enriched with anti-LPS antibodies) in&#xD;
      combination with standard of care lifestyle advice is safe and leads to greater improvement&#xD;
      in hepatic inflammation, insulin sensitivity, and blood lipids in children with nonalcoholic&#xD;
      fatty liver disease (NAFLD) compared to placebo with standard of care treatment.&#xD;
      Investigators also seek to define the mechanism of action in response to three months of&#xD;
      treatment with IMM-124E.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 1, 2017</start_date>
  <completion_date type="Actual">October 23, 2019</completion_date>
  <primary_completion_date type="Actual">October 23, 2019</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percent Change in Alanine Aminotransferase (ALT) Level</measure>
    <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
    <description>Percent change in ALT level from baseline to end of treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent Change in Fasting Glucose Level</measure>
    <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
    <description>Fasting glucose level will be collected via blood draw. Percent Change in glucose levels between baseline and end of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Fasting Insulin Level</measure>
    <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
    <description>Fasting insulin level will be collected via blood draw. Change is the difference in insulin level from baseline to end of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Hemoglobin A1C Level</measure>
    <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
    <description>Hemoglobin A1C Level will be collected via blood draw. Change is the difference in hemoglobin AIC level from baseline to end of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Adipose Tissue Insulin Resistance (Adipo-IR)</measure>
    <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
    <description>Adipo-IR will be collected via blood draw. It is calculated as fasting non-esterified fatty acids x fasting insulin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Triglyceride/HDL (TG/HDL) Ratio</measure>
    <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
    <description>The TG/HDL ratio is the proportion of triglyceride levels in relation to HDL (good cholesterol). Change is defined as the difference in the TG/HDL ratio from baseline to the end of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change in Blood Glucose Level</measure>
    <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
    <description>The blood glucose level will be monitored via an oral glucose tolerance test (OGTT) at baseline and at the end of treatment. During the OGTT, the glucose level will be tested by a blood draw every thirty minutes for two hours. Percentage change between glucose measurements taken at baseline and at the end of treatment is reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Insulin Levels</measure>
    <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
    <description>The insulin level will be monitored via an oral glucose tolerance test (OGTT) at baseline and at the end of treatment. During the OGTT, the insulin level will be tested by a blood draw every thirty minutes for two hours. Change is described as the difference between insulin measurements taken at baseline and at the end of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change in Body Mass Index (BMI) Z-Score</measure>
    <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
    <description>BMI will be calculated from height and weight and converted into a z-score. Body mass index z-scores are measures of relative weight adjusted for age and sex.Change is the difference in BMI z-scores from base line to end of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change in Visceral Adiposity</measure>
    <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
    <description>Visceral adiposity will be measured with a magnetic resonance imaging (MRI) scan. Visceral adipose tissue is a hormonally active component of total body fat.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change in Hepatic Fat Percent</measure>
    <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
    <description>Hepatic fat percent will be measured with a magnetic resonance imaging (MRI) scan. Hepatic fat percent is the percentage of fat within the liver.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change in Waist Circumference</measure>
    <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
    <description>Waist circumference will be measured in centimeters using measuring tape.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change in PROMIS Fatigue Questionnaire Score</measure>
    <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
    <description>The PROMIS Fatigue questionnaire evaluates a range of self-reported symptoms, from mild subjective feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion that likely decreases one's ability to execute daily activities and function normally in family or social roles. Fatigue is divided into the experience of fatigue (frequency, duration, and intensity) and the impact of fatigue on physical, mental, and social activities. It assesses fatigue over the past seven days. A higher score represents more symptoms of fatigue.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change in PROMIS Depression Questionnaire Score</measure>
    <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
    <description>The PROMIS Depression instruments assess self-reported negative mood (sadness, guilt), views of self (selfcriticism, worthlessness), and social cognition (loneliness, interpersonal alienation), as well as decreased positive affect and engagement (loss of interest, meaning, and purpose). It assesses depression over the past seven days. A higher score represents more symptoms of depression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change in PROMIS Anxiety Questionnaire Score</measure>
    <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
    <description>The PROMIS Anxiety instruments measure self-reported fear (fearfulness, panic), anxious misery (worry, dread), hyperarousal (tension, nervousness, restlessness), and somatic symptoms related to arousal (racing heart, dizziness). Anxiety is best differentiated by symptoms that reflect autonomic arousal and experience of threat. Each assesses anxiety over the past seven days. A higher score represents more symptoms of anxiety.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite Metabolic Improvement</measure>
    <time_frame>End of Treatment (Week 12)</time_frame>
    <description>Composite metabolic improvement is defined as greater than 10% improvement in TG/HDL ratio, improvement in insulin resistance, and greater than 10% improvement in ALT.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Nonalcoholic Fatty Liver Disease (NAFLD)</condition>
  <arm_group>
    <arm_group_label>IMM-124E Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive 600mg of IMM-124E powder three times daily for twelve weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive placebo powder three times daily for twelve weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>IMM-124E</intervention_name>
    <description>IMM-124E is a hyper-immune, bovine colostrum (milk) powder with flavoring.</description>
    <arm_group_label>IMM-124E Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matched Placebo</description>
    <arm_group_label>Placebo Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Nonalcoholic fatty liver disease (NAFLD) diagnosis confirmed by liver biopsy or MRI&#xD;
&#xD;
          -  ALT ≥ 2 x ULN at screening (girls ≥ 46, boys ≥ 54)&#xD;
&#xD;
          -  Written informed parent consent and child assent&#xD;
&#xD;
          -  Willingness to take IMM-124E or placebo powder 3 x daily for 12 weeks&#xD;
&#xD;
          -  At least 2 months of attempted lifestyle changes after diagnosis&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Disease or condition deemed by physician to interfere with absorption, digestion, or&#xD;
             mechanism of intervention of drug&#xD;
&#xD;
          -  Diagnosis of diabetes and an HbA1c of &gt; 9%&#xD;
&#xD;
          -  Change in supplement or anti-oxidant therapy within past 90 days (must be on a stable&#xD;
             dose and willing to continue it throughout the trial or not on any vitamin or&#xD;
             supplement, includes SAMe, vitamin E, betaine, Milk thistle etc)&#xD;
&#xD;
          -  Use of probiotics or antibiotics in the past 30 days&#xD;
&#xD;
          -  Use of anti-NAFLD medications (metformin, thiazolidinediones, UDCA) in the 30 days&#xD;
             prior to randomization&#xD;
&#xD;
          -  Acute illness within past 2 weeks prior to enrollment (defined as fever &gt; 100.4ºF)&#xD;
&#xD;
          -  Planned pregnancy, nursing an infant, confirmed or suspected to be pregnant between&#xD;
             screening and time of study enrollment&#xD;
&#xD;
          -  Evidence of other chronic liver disease other than NAFLD (Hepatitis B and C, Alpha-1&#xD;
             antitrypsin, Wilson's disease)&#xD;
&#xD;
          -  Intolerance to lactose or dairy-based products&#xD;
&#xD;
          -  Unable to have blood drawn at study visits&#xD;
&#xD;
          -  Unwillingness to provide and/or collect stool samples&#xD;
&#xD;
          -  Current gastrointestinal (GI) bleeding or inflammatory bowel disease (irritable bowel&#xD;
             disease (IBD), colitis)&#xD;
&#xD;
          -  Current enrollment in another therapeutic clinical trial or receipt of an&#xD;
             investigational study drug within 6 months prior to study enrollment&#xD;
&#xD;
          -  Participants who are not able or willing to comply with the protocol or have any other&#xD;
             condition that would impede compliance or hinder completion of the study, in the&#xD;
             opinion of the investigator&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>19 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Miriam Vos, MD, MSPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Healthcare of Atlanta</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>February 2, 2017</study_first_submitted>
  <study_first_submitted_qc>February 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 3, 2017</study_first_posted>
  <results_first_submitted>October 20, 2020</results_first_submitted>
  <results_first_submitted_qc>December 8, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">January 5, 2021</results_first_posted>
  <last_update_submitted>April 26, 2021</last_update_submitted>
  <last_update_submitted_qc>April 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 24, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Emory University</investigator_affiliation>
    <investigator_full_name>Miriam Vos, MD</investigator_full_name>
    <investigator_title>Associate 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>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 26, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/67/NCT03042767/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>40 participants were enrolled, 15 of them screenfailed. 25 participants were randomized.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>IMM-124E Group</title>
          <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive 600mg of IMM-124E powder three times daily for twelve weeks.&#xD;
IMM-124E: IMM-124E is a hyper-immune, bovine colostrum (milk) powder with flavoring.</description>
        </group>
        <group group_id="P2">
          <title>Placebo Group</title>
          <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive placebo powder three times daily for twelve weeks.&#xD;
Placebo: Matched Placebo</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>IMM-124E Group</title>
          <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive 600mg of IMM-124E powder three times daily for twelve weeks.&#xD;
IMM-124E: IMM-124E is a hyper-immune, bovine colostrum (milk) powder with flavoring.</description>
        </group>
        <group group_id="B2">
          <title>Placebo Group</title>
          <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive placebo powder three times daily for twelve weeks.&#xD;
Placebo: Matched Placebo</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="12"/>
            <count group_id="B2" value="13"/>
            <count group_id="B3" value="25"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percent Change in Alanine Aminotransferase (ALT) Level</title>
        <description>Percent change in ALT level from baseline to end of treatment.</description>
        <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>IMM-124E Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive 600mg of IMM-124E powder three times daily for twelve weeks.&#xD;
IMM-124E: IMM-124E is a hyper-immune, bovine colostrum (milk) powder with flavoring.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive placebo powder three times daily for twelve weeks.&#xD;
Placebo: Matched Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in Alanine Aminotransferase (ALT) Level</title>
          <description>Percent change in ALT level from baseline to end of treatment.</description>
          <units>percentage change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.99" spread="25.87"/>
                    <measurement group_id="O2" value="-7.99" spread="16.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change in Fasting Glucose Level</title>
        <description>Fasting glucose level will be collected via blood draw. Percent Change in glucose levels between baseline and end of treatment.</description>
        <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>IMM-124E Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive 600mg of IMM-124E powder three times daily for twelve weeks.&#xD;
IMM-124E: IMM-124E is a hyper-immune, bovine colostrum (milk) powder with flavoring.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive placebo powder three times daily for twelve weeks.&#xD;
Placebo: Matched Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in Fasting Glucose Level</title>
          <description>Fasting glucose level will be collected via blood draw. Percent Change in glucose levels between baseline and end of treatment.</description>
          <units>percentage change</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.55" lower_limit="-1.14" upper_limit="16.05"/>
                    <measurement group_id="O2" value="1.11" lower_limit="-6.54" upper_limit="3.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Fasting Insulin Level</title>
        <description>Fasting insulin level will be collected via blood draw. Change is the difference in insulin level from baseline to end of treatment.</description>
        <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
        <population>Data were not analyzed due to funding limitation.</population>
        <group_list>
          <group group_id="O1">
            <title>IMM-124E Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive 600mg of IMM-124E powder three times daily for twelve weeks.&#xD;
IMM-124E: IMM-124E is a hyper-immune, bovine colostrum (milk) powder with flavoring.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive placebo powder three times daily for twelve weeks.&#xD;
Placebo: Matched Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Fasting Insulin Level</title>
          <description>Fasting insulin level will be collected via blood draw. Change is the difference in insulin level from baseline to end of treatment.</description>
          <population>Data were not analyzed due to funding limitation.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Hemoglobin A1C Level</title>
        <description>Hemoglobin A1C Level will be collected via blood draw. Change is the difference in hemoglobin AIC level from baseline to end of treatment.</description>
        <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
        <population>Data were not collected. Hemoglobin A1c was only used as a screening lab, it was not measured throughout the study - change cannot be measured</population>
        <group_list>
          <group group_id="O1">
            <title>IMM-124E Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive 600mg of IMM-124E powder three times daily for twelve weeks.&#xD;
IMM-124E: IMM-124E is a hyper-immune, bovine colostrum (milk) powder with flavoring.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive placebo powder three times daily for twelve weeks.&#xD;
Placebo: Matched Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Hemoglobin A1C Level</title>
          <description>Hemoglobin A1C Level will be collected via blood draw. Change is the difference in hemoglobin AIC level from baseline to end of treatment.</description>
          <population>Data were not collected. Hemoglobin A1c was only used as a screening lab, it was not measured throughout the study - change cannot be measured</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Adipose Tissue Insulin Resistance (Adipo-IR)</title>
        <description>Adipo-IR will be collected via blood draw. It is calculated as fasting non-esterified fatty acids x fasting insulin.</description>
        <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
        <population>Data were not analyzed due to funding limitation.</population>
        <group_list>
          <group group_id="O1">
            <title>IMM-124E Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive 600mg of IMM-124E powder three times daily for twelve weeks.&#xD;
IMM-124E: IMM-124E is a hyper-immune, bovine colostrum (milk) powder with flavoring.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive placebo powder three times daily for twelve weeks.&#xD;
Placebo: Matched Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Adipose Tissue Insulin Resistance (Adipo-IR)</title>
          <description>Adipo-IR will be collected via blood draw. It is calculated as fasting non-esterified fatty acids x fasting insulin.</description>
          <population>Data were not analyzed due to funding limitation.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Triglyceride/HDL (TG/HDL) Ratio</title>
        <description>The TG/HDL ratio is the proportion of triglyceride levels in relation to HDL (good cholesterol). Change is defined as the difference in the TG/HDL ratio from baseline to the end of treatment.</description>
        <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
        <population>Data were not analyzed due to funding limitation.</population>
        <group_list>
          <group group_id="O1">
            <title>IMM-124E Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive 600mg of IMM-124E powder three times daily for twelve weeks.&#xD;
IMM-124E: IMM-124E is a hyper-immune, bovine colostrum (milk) powder with flavoring.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive placebo powder three times daily for twelve weeks.&#xD;
Placebo: Matched Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Triglyceride/HDL (TG/HDL) Ratio</title>
          <description>The TG/HDL ratio is the proportion of triglyceride levels in relation to HDL (good cholesterol). Change is defined as the difference in the TG/HDL ratio from baseline to the end of treatment.</description>
          <population>Data were not analyzed due to funding limitation.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change in Blood Glucose Level</title>
        <description>The blood glucose level will be monitored via an oral glucose tolerance test (OGTT) at baseline and at the end of treatment. During the OGTT, the glucose level will be tested by a blood draw every thirty minutes for two hours. Percentage change between glucose measurements taken at baseline and at the end of treatment is reported.</description>
        <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>IMM-124E Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive 600mg of IMM-124E powder three times daily for twelve weeks.&#xD;
IMM-124E: IMM-124E is a hyper-immune, bovine colostrum (milk) powder with flavoring.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive placebo powder three times daily for twelve weeks.&#xD;
Placebo: Matched Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in Blood Glucose Level</title>
          <description>The blood glucose level will be monitored via an oral glucose tolerance test (OGTT) at baseline and at the end of treatment. During the OGTT, the glucose level will be tested by a blood draw every thirty minutes for two hours. Percentage change between glucose measurements taken at baseline and at the end of treatment is reported.</description>
          <units>percentage change</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.11" lower_limit="-3.06" upper_limit="16.05"/>
                    <measurement group_id="O2" value="1.16" lower_limit="-6.54" upper_limit="3.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Insulin Levels</title>
        <description>The insulin level will be monitored via an oral glucose tolerance test (OGTT) at baseline and at the end of treatment. During the OGTT, the insulin level will be tested by a blood draw every thirty minutes for two hours. Change is described as the difference between insulin measurements taken at baseline and at the end of treatment.</description>
        <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
        <population>Data were not analyzed due to funding limitation.</population>
        <group_list>
          <group group_id="O1">
            <title>IMM-124E Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive 600mg of IMM-124E powder three times daily for twelve weeks.&#xD;
IMM-124E: IMM-124E is a hyper-immune, bovine colostrum (milk) powder with flavoring.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive placebo powder three times daily for twelve weeks.&#xD;
Placebo: Matched Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Insulin Levels</title>
          <description>The insulin level will be monitored via an oral glucose tolerance test (OGTT) at baseline and at the end of treatment. During the OGTT, the insulin level will be tested by a blood draw every thirty minutes for two hours. Change is described as the difference between insulin measurements taken at baseline and at the end of treatment.</description>
          <population>Data were not analyzed due to funding limitation.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change in Body Mass Index (BMI) Z-Score</title>
        <description>BMI will be calculated from height and weight and converted into a z-score. Body mass index z-scores are measures of relative weight adjusted for age and sex.Change is the difference in BMI z-scores from base line to end of treatment.</description>
        <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>IMM-124E Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive 600mg of IMM-124E powder three times daily for twelve weeks.&#xD;
IMM-124E: IMM-124E is a hyper-immune, bovine colostrum (milk) powder with flavoring.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive placebo powder three times daily for twelve weeks.&#xD;
Placebo: Matched Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in Body Mass Index (BMI) Z-Score</title>
          <description>BMI will be calculated from height and weight and converted into a z-score. Body mass index z-scores are measures of relative weight adjusted for age and sex.Change is the difference in BMI z-scores from base line to end of treatment.</description>
          <units>percentage change</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.66" lower_limit="-0.46" upper_limit="2.38"/>
                    <measurement group_id="O2" value="-0.48" lower_limit="-3.77" upper_limit="2.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change in Visceral Adiposity</title>
        <description>Visceral adiposity will be measured with a magnetic resonance imaging (MRI) scan. Visceral adipose tissue is a hormonally active component of total body fat.</description>
        <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>IMM-124E Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive 600mg of IMM-124E powder three times daily for twelve weeks.&#xD;
IMM-124E: IMM-124E is a hyper-immune, bovine colostrum (milk) powder with flavoring.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive placebo powder three times daily for twelve weeks.&#xD;
Placebo: Matched Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in Visceral Adiposity</title>
          <description>Visceral adiposity will be measured with a magnetic resonance imaging (MRI) scan. Visceral adipose tissue is a hormonally active component of total body fat.</description>
          <units>percentage change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.23" spread="8.63"/>
                    <measurement group_id="O2" value="1.77" spread="9.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change in Hepatic Fat Percent</title>
        <description>Hepatic fat percent will be measured with a magnetic resonance imaging (MRI) scan. Hepatic fat percent is the percentage of fat within the liver.</description>
        <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>IMM-124E Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive 600mg of IMM-124E powder three times daily for twelve weeks.&#xD;
IMM-124E: IMM-124E is a hyper-immune, bovine colostrum (milk) powder with flavoring.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive placebo powder three times daily for twelve weeks.&#xD;
Placebo: Matched Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in Hepatic Fat Percent</title>
          <description>Hepatic fat percent will be measured with a magnetic resonance imaging (MRI) scan. Hepatic fat percent is the percentage of fat within the liver.</description>
          <units>percentage change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.70" spread="16.80"/>
                    <measurement group_id="O2" value="-6.61" spread="17.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change in Waist Circumference</title>
        <description>Waist circumference will be measured in centimeters using measuring tape.</description>
        <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>IMM-124E Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive 600mg of IMM-124E powder three times daily for twelve weeks.&#xD;
IMM-124E: IMM-124E is a hyper-immune, bovine colostrum (milk) powder with flavoring.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive placebo powder three times daily for twelve weeks.&#xD;
Placebo: Matched Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in Waist Circumference</title>
          <description>Waist circumference will be measured in centimeters using measuring tape.</description>
          <units>percentage change</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.29" lower_limit="-0.88" upper_limit="4.29"/>
                    <measurement group_id="O2" value="0.76" lower_limit="-0.33" upper_limit="1.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change in PROMIS Fatigue Questionnaire Score</title>
        <description>The PROMIS Fatigue questionnaire evaluates a range of self-reported symptoms, from mild subjective feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion that likely decreases one's ability to execute daily activities and function normally in family or social roles. Fatigue is divided into the experience of fatigue (frequency, duration, and intensity) and the impact of fatigue on physical, mental, and social activities. It assesses fatigue over the past seven days. A higher score represents more symptoms of fatigue.</description>
        <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>IMM-124E Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive 600mg of IMM-124E powder three times daily for twelve weeks.&#xD;
IMM-124E: IMM-124E is a hyper-immune, bovine colostrum (milk) powder with flavoring.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive placebo powder three times daily for twelve weeks.&#xD;
Placebo: Matched Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in PROMIS Fatigue Questionnaire Score</title>
          <description>The PROMIS Fatigue questionnaire evaluates a range of self-reported symptoms, from mild subjective feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion that likely decreases one's ability to execute daily activities and function normally in family or social roles. Fatigue is divided into the experience of fatigue (frequency, duration, and intensity) and the impact of fatigue on physical, mental, and social activities. It assesses fatigue over the past seven days. A higher score represents more symptoms of fatigue.</description>
          <units>percentage change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.17" spread="14.90"/>
                    <measurement group_id="O2" value="-4.67" spread="17.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change in PROMIS Depression Questionnaire Score</title>
        <description>The PROMIS Depression instruments assess self-reported negative mood (sadness, guilt), views of self (selfcriticism, worthlessness), and social cognition (loneliness, interpersonal alienation), as well as decreased positive affect and engagement (loss of interest, meaning, and purpose). It assesses depression over the past seven days. A higher score represents more symptoms of depression.</description>
        <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>IMM-124E Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive 600mg of IMM-124E powder three times daily for twelve weeks.&#xD;
IMM-124E: IMM-124E is a hyper-immune, bovine colostrum (milk) powder with flavoring.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive placebo powder three times daily for twelve weeks.&#xD;
Placebo: Matched Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in PROMIS Depression Questionnaire Score</title>
          <description>The PROMIS Depression instruments assess self-reported negative mood (sadness, guilt), views of self (selfcriticism, worthlessness), and social cognition (loneliness, interpersonal alienation), as well as decreased positive affect and engagement (loss of interest, meaning, and purpose). It assesses depression over the past seven days. A higher score represents more symptoms of depression.</description>
          <units>percentage change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.68" spread="17.00"/>
                    <measurement group_id="O2" value="3.62" spread="11.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change in PROMIS Anxiety Questionnaire Score</title>
        <description>The PROMIS Anxiety instruments measure self-reported fear (fearfulness, panic), anxious misery (worry, dread), hyperarousal (tension, nervousness, restlessness), and somatic symptoms related to arousal (racing heart, dizziness). Anxiety is best differentiated by symptoms that reflect autonomic arousal and experience of threat. Each assesses anxiety over the past seven days. A higher score represents more symptoms of anxiety.</description>
        <time_frame>Baseline (Week 0), End of Treatment (Week 12)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>IMM-124E Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive 600mg of IMM-124E powder three times daily for twelve weeks.&#xD;
IMM-124E: IMM-124E is a hyper-immune, bovine colostrum (milk) powder with flavoring.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive placebo powder three times daily for twelve weeks.&#xD;
Placebo: Matched Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in PROMIS Anxiety Questionnaire Score</title>
          <description>The PROMIS Anxiety instruments measure self-reported fear (fearfulness, panic), anxious misery (worry, dread), hyperarousal (tension, nervousness, restlessness), and somatic symptoms related to arousal (racing heart, dizziness). Anxiety is best differentiated by symptoms that reflect autonomic arousal and experience of threat. Each assesses anxiety over the past seven days. A higher score represents more symptoms of anxiety.</description>
          <units>percentage change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-13.78" spread="16.39"/>
                    <measurement group_id="O2" value="-4.89" spread="13.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Composite Metabolic Improvement</title>
        <description>Composite metabolic improvement is defined as greater than 10% improvement in TG/HDL ratio, improvement in insulin resistance, and greater than 10% improvement in ALT.</description>
        <time_frame>End of Treatment (Week 12)</time_frame>
        <population>Data were not analyzed due to funding limitation.</population>
        <group_list>
          <group group_id="O1">
            <title>IMM-124E Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive 600mg of IMM-124E powder three times daily for twelve weeks.&#xD;
IMM-124E: IMM-124E is a hyper-immune, bovine colostrum (milk) powder with flavoring.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive placebo powder three times daily for twelve weeks.&#xD;
Placebo: Matched Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Composite Metabolic Improvement</title>
          <description>Composite metabolic improvement is defined as greater than 10% improvement in TG/HDL ratio, improvement in insulin resistance, and greater than 10% improvement in ALT.</description>
          <population>Data were not analyzed due to funding limitation.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>12 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>IMM-124E Group</title>
          <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive 600mg of IMM-124E powder three times daily for twelve weeks.&#xD;
IMM-124E: IMM-124E is a hyper-immune, bovine colostrum (milk) powder with flavoring.</description>
        </group>
        <group group_id="E2">
          <title>Placebo Group</title>
          <description>Participants with nonalcoholic fatty liver disease (NAFLD) will receive placebo powder three times daily for twelve weeks.&#xD;
Placebo: Matched Placebo</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Abnormal glucose result</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" events="8" subjects_affected="5" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Vomit</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Miriam Vos</name_or_title>
      <organization>Emory University</organization>
      <phone>404-727-5383</phone>
      <email>mvos@emory.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03042767
org study id: IRB00084686
nct id: NCT03042767
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The main objective of this pilot study is to evaluate whether 12 weeks of IMM-124E in
      children with nonalcoholic fatty liver disease (NAFLD) in combination with standard of care
      treatment will decrease inflammation in the liver as measured by alanine transaminase (ALT).
      Specifically, investigators will measure percent change in ALT from Week 0 to Week 12 in
      treatment compared to placebo.
This is a randomized, double blind, placebo controlled, three month treatment trial of
      children aged 6-19 years. Participants will be recruited from the Children's Healthcare of
      Atlanta pediatric liver clinical practice.The purpose of this study is to evaluate if a three
      month treatment with IMM-124E (a bovine colostrum enriched with anti-LPS antibodies) in
      combination with standard of care lifestyle advice is safe and leads to greater improvement
      in hepatic inflammation, insulin sensitivity, and blood lipids in children with nonalcoholic
      fatty liver disease (NAFLD) compared to placebo with standard of care treatment.
      Investigators also seek to define the mechanism of action in response to three months of
      treatment with IMM-124E.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Percent Change in Alanine Aminotransferase (ALT) Level
time frame: Baseline (Week 0), End of Treatment (Week 12)
description: Percent change in ALT level from baseline to end of treatment.
measure: Percent Change in Fasting Glucose Level
time frame: Baseline (Week 0), End of Treatment (Week 12)
description: Fasting glucose level will be collected via blood draw. Percent Change in glucose levels between baseline and end of treatment.
measure: Change in Fasting Insulin Level
time frame: Baseline (Week 0), End of Treatment (Week 12)
description: Fasting insulin level will be collected via blood draw. Change is the difference in insulin level from baseline to end of treatment.
measure: Change in Hemoglobin A1C Level
time frame: Baseline (Week 0), End of Treatment (Week 12)
description: Hemoglobin A1C Level will be collected via blood draw. Change is the difference in hemoglobin AIC level from baseline to end of treatment.
measure: Change in Adipose Tissue Insulin Resistance (Adipo-IR)
time frame: Baseline (Week 0), End of Treatment (Week 12)
description: Adipo-IR will be collected via blood draw. It is calculated as fasting non-esterified fatty acids x fasting insulin.
measure: Change in Triglyceride/HDL (TG/HDL) Ratio
time frame: Baseline (Week 0), End of Treatment (Week 12)
description: The TG/HDL ratio is the proportion of triglyceride levels in relation to HDL (good cholesterol). Change is defined as the difference in the TG/HDL ratio from baseline to the end of treatment.
measure: Percent Change in Blood Glucose Level
time frame: Baseline (Week 0), End of Treatment (Week 12)
description: The blood glucose level will be monitored via an oral glucose tolerance test (OGTT) at baseline and at the end of treatment. During the OGTT, the glucose level will be tested by a blood draw every thirty minutes for two hours. Percentage change between glucose measurements taken at baseline and at the end of treatment is reported.
measure: Change in Insulin Levels
time frame: Baseline (Week 0), End of Treatment (Week 12)
description: The insulin level will be monitored via an oral glucose tolerance test (OGTT) at baseline and at the end of treatment. During the OGTT, the insulin level will be tested by a blood draw every thirty minutes for two hours. Change is described as the difference between insulin measurements taken at baseline and at the end of treatment.
measure: Percent Change in Body Mass Index (BMI) Z-Score
time frame: Baseline (Week 0), End of Treatment (Week 12)
description: BMI will be calculated from height and weight and converted into a z-score. Body mass index z-scores are measures of relative weight adjusted for age and sex.Change is the difference in BMI z-scores from base line to end of treatment.
measure: Percent Change in Visceral Adiposity
time frame: Baseline (Week 0), End of Treatment (Week 12)
description: Visceral adiposity will be measured with a magnetic resonance imaging (MRI) scan. Visceral adipose tissue is a hormonally active component of total body fat.
measure: Percent Change in Hepatic Fat Percent
time frame: Baseline (Week 0), End of Treatment (Week 12)
description: Hepatic fat percent will be measured with a magnetic resonance imaging (MRI) scan. Hepatic fat percent is the percentage of fat within the liver.
measure: Percent Change in Waist Circumference
time frame: Baseline (Week 0), End of Treatment (Week 12)
description: Waist circumference will be measured in centimeters using measuring tape.
measure: Percent Change in PROMIS Fatigue Questionnaire Score
time frame: Baseline (Week 0), End of Treatment (Week 12)
description: The PROMIS Fatigue questionnaire evaluates a range of self-reported symptoms, from mild subjective feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion that likely decreases one's ability to execute daily activities and function normally in family or social roles. Fatigue is divided into the experience of fatigue (frequency, duration, and intensity) and the impact of fatigue on physical, mental, and social activities. It assesses fatigue over the past seven days. A higher score represents more symptoms of fatigue.
measure: Percent Change in PROMIS Depression Questionnaire Score
time frame: Baseline (Week 0), End of Treatment (Week 12)
description: The PROMIS Depression instruments assess self-reported negative mood (sadness, guilt), views of self (selfcriticism, worthlessness), and social cognition (loneliness, interpersonal alienation), as well as decreased positive affect and engagement (loss of interest, meaning, and purpose). It assesses depression over the past seven days. A higher score represents more symptoms of depression.
measure: Percent Change in PROMIS Anxiety Questionnaire Score
time frame: Baseline (Week 0), End of Treatment (Week 12)
description: The PROMIS Anxiety instruments measure self-reported fear (fearfulness, panic), anxious misery (worry, dread), hyperarousal (tension, nervousness, restlessness), and somatic symptoms related to arousal (racing heart, dizziness). Anxiety is best differentiated by symptoms that reflect autonomic arousal and experience of threat. Each assesses anxiety over the past seven days. A higher score represents more symptoms of anxiety.
measure: Composite Metabolic Improvement
time frame: End of Treatment (Week 12)
description: Composite metabolic improvement is defined as greater than 10% improvement in TG/HDL ratio, improvement in insulin resistance, and greater than 10% improvement in ALT.
arm group label: IMM-124E Group
arm group type: Experimental
description: Participants with nonalcoholic fatty liver disease (NAFLD) will receive 600mg of IMM-124E powder three times daily for twelve weeks.
arm group label: Placebo Group
arm group type: Placebo Comparator
description: Participants with nonalcoholic fatty liver disease (NAFLD) will receive placebo powder three times daily for twelve weeks.
intervention type: Biological
intervention name: IMM-124E
description: IMM-124E is a hyper-immune, bovine colostrum (milk) powder with flavoring.
arm group label: IMM-124E Group
intervention type: Other
intervention name: Placebo
description: Matched Placebo
arm group label: Placebo Group
criteria: 
gender: All
minimum age: 6 Years
maximum age: 19 Years
healthy volunteers: No
last name: Miriam Vos, MD, MSPH
role: Principal Investigator
affiliation: Emory University
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Emory University
investigator full name: Miriam Vos, MD
investigator title: Associate Professor
mesh term: Liver Diseases
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 