<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/NCT02196831</url>
  </required_header>
  <id_info>
    <org_study_id>1U01AI115711</org_study_id>
    <secondary_id>U01AI115711</secondary_id>
    <nct_id>NCT02196831</nct_id>
  </id_info>
  <brief_title>Tesamorelin Effects on Liver Fat and Histology in HIV</brief_title>
  <official_title>Tesamorelin Effects on Liver Fat and Histology in HIV: A Collaborative UO1 Grant</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Liver disease is one of the leading co-morbidities of human immunodeficiency virus (HIV)&#xD;
      infection, and nonalcoholic fatty liver disease (NAFLD) is present in approximately 30-40% of&#xD;
      patients with HIV infection. Nonalcoholic steatohepatitis (NASH) is a more severe form of&#xD;
      NAFLD in which increased liver fat is also accompanied by inflammation, cellular damage, and&#xD;
      fibrosis.&#xD;
&#xD;
      NAFLD is most prevalent in patients who also have increased visceral adiposity, and our group&#xD;
      has previously shown that HIV-infected individuals with increased visceral adiposity&#xD;
      generally have decreased growth hormone secretion. Tesamorelin is a growth hormone releasing&#xD;
      hormone (GHRH) analogue that increases endogenous growth hormone secretion. Tesamorelin is&#xD;
      FDA-approved for the reduction of visceral fat in HIV-infected individuals. In a previous&#xD;
      study, treatment with tesamorelin in HIV-infected individuals selected for abdominal&#xD;
      adiposity reduced liver fat. The current study is designed to test the effect of tesamorelin&#xD;
      on liver fat and steatohepatitis in HIV-infected individuals who have NAFLD. The&#xD;
      investigators hypothesize that tesamorelin will reduce liver fat and will also ameliorate the&#xD;
      inflammation, fibrosis, and hepatocellular damage seen in conjunction with NASH.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2015</start_date>
  <completion_date type="Actual">July 24, 2019</completion_date>
  <primary_completion_date type="Actual">January 16, 2019</primary_completion_date>
  <phase>N/A</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Liver Fat as Measured by 1-H Magnetic Resonance Spectroscopy</measure>
    <time_frame>change between baseline and 12 months</time_frame>
    <description>change (value at 12 months minus value at baseline). Hepatic fat fraction is a standardized measure used to describe the percent fat in the liver. As it is determined by spectroscopy, it is quantified by the area under the lipid peak, standardized to the total area under the (lipid peak + water peak). Using 1-H Magnetic resonance spectroscopy to quantify liver fat in this manner was first described by Longo R et al., Invest Radiol, 1993, 28(4):297-302.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score</measure>
    <time_frame>change between baseline and 12 months</time_frame>
    <description>change (value at 12 months minus value at baseline). The nonalcoholic fatty liver disease (NAFLD) activity score is a standardized histological quantification of NAFLD severity designed and validated by the Nonalcoholic Steatohepatitis Clinical Research Network (Kleiner DE et al., Hepatology, 2005, 41(6):1313-1321). The score is the sum of three semi-quantitative histological grades:&#xD;
steatosis, graded from 0 [&lt;5% liver fat] to grade 3 [&gt;66% liver fat]&#xD;
lobular inflammation, graded from 0 [no foci of inflammation] to 3 [&gt;4 foci per 200x field]&#xD;
hepatocellular ballooning, graded from 0 [no ballooning] to 2 [many cells/prominent ballooning] The &quot;total&quot; NAFLD activity score, a sum of the three components below, ranges from 0 to 8, with a higher score generally representing greater severity of NAFLD/nonalcoholic steatohepatitis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Alanine Aminotransferase (ALT)</measure>
    <time_frame>change from baseline to 12 months</time_frame>
    <description>change (value at 12 months minus value at baseline)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Aspartate Aminotransferase (AST)</measure>
    <time_frame>change from baseline to 12 months</time_frame>
    <description>change (value at 12 months minus value at baseline)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">61</enrollment>
  <condition>Human Immunodeficiency Virus (HIV)</condition>
  <condition>Nonalcoholic Fatty Liver Disease (NAFLD)</condition>
  <condition>Nonalcoholic Steatohepatitis (NASH)</condition>
  <arm_group>
    <arm_group_label>Tesamorelin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>tesamorelin 2mg subcutaneously daily x 12 months double-blind phase. At the end of 12 months, subjects enter open-label tesamorelin treatment phase for 6 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>placebo subcutaneously daily x 12 months double-blind phase. At the end of 12 months, subjects enter open-label tesamorelin treatment phase for 6 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>tesamorelin</intervention_name>
    <arm_group_label>Tesamorelin</arm_group_label>
    <other_name>Egrifta</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>inactive substance that looks like tesamorelin</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Men and women 18-70yo&#xD;
&#xD;
          -  HIV-infection and treatment with a stable antiretroviral regimen for ≥ 6 months&#xD;
&#xD;
          -  Hepatic steatosis as demonstrated by liver fat fraction ≥5% on 1H-MRS&#xD;
&#xD;
          -  Hepatitis C antibody negative, or, if Hepatitis C antibody positive, either: a) known&#xD;
             clinical disease, successful therapy ≥1 year prior to baseline and undetectable HCV&#xD;
             RNA, or b) HCV resolved spontaneously and undetectable HCV RNA. Hepatitis B surface&#xD;
             antigen negative at screen visit&#xD;
&#xD;
          -  For females ≥50yo, negative mammogram within 1 year of baseline visit&#xD;
&#xD;
          -  If use of Vitamin E ≥400 IU daily (in any formulation), stable dose for ≥6 months&#xD;
             prior to study.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Heavy alcohol use defined as consumption of more than 20g daily for women or more than&#xD;
             30g daily for men for at least 3 consecutive months over the past 5 years&#xD;
&#xD;
          -  Use of insulin or thiazoledinediones (TZDs), or HbA1c ≥7%. Individuals with mild&#xD;
             diabetes that is well-controlled with diet and/or oral anti-diabetic agents besides&#xD;
             TZDs will be included. Use of oral anti-diabetics must have been stable for ≥6 months&#xD;
             prior to study entry.&#xD;
&#xD;
          -  Known diabetic retinopathy.&#xD;
&#xD;
          -  Known cirrhosis, or Child-Pugh score ≥7, stage 4 fibrosis on biopsy, or clinical&#xD;
             evidence of cirrhosis or portal hypertension on imaging or exam.&#xD;
&#xD;
          -  Chronic corticosteroid use except intermittent use of topical steroid creams and/or&#xD;
             prior short-term physiologic corticosteroid use in the ≤ 6 months prior to baseline&#xD;
             visit&#xD;
&#xD;
          -  Chronic use of methotrexate, amiodarone, or tamoxifen&#xD;
&#xD;
          -  Known diagnosis of Alpha-1 antitrypsin deficiency, Wilson's disease, hemochromatosis,&#xD;
             or autoimmune hepatitis&#xD;
&#xD;
          -  Use of GH or GHRH within the past 1 year&#xD;
&#xD;
          -  Change in lipid lowering or anti-hypertensive regimen within 3 months of screening&#xD;
&#xD;
          -  HgB &lt; 11.0 g/dL, CD4 &lt; 100 th/mm3, or HIV viral load &gt; 400 copies/mL&#xD;
&#xD;
          -  Active malignancy&#xD;
&#xD;
          -  For men, history of prostate cancer or evidence of prostate malignancy by PSA &gt; 5&#xD;
             ng/mL&#xD;
&#xD;
          -  Severe chronic illness judged by the investigator to present a contraindication to&#xD;
             participation&#xD;
&#xD;
          -  History of hypopituitarism, head irradiation or any other condition known to affect&#xD;
             the GH axis&#xD;
&#xD;
          -  Use of physiologic testosterone (men) or estrogen or progesterone (women) unless&#xD;
             stable use for a year or more prior to study entry&#xD;
&#xD;
          -  Routine MRI exclusion criteria such as the presence of a pacemaker or cerebral&#xD;
             aneurysm clip&#xD;
&#xD;
          -  Previous weight loss surgery&#xD;
&#xD;
          -  For women, positive pregnancy test performed in a CLIA certified laboratory using a&#xD;
             test with a sensitivity of at least 25mIU/mL, or breastfeeding.&#xD;
&#xD;
          -  Known hypersensitivity to tesamorelin or mannitol&#xD;
&#xD;
          -  Unwillingness to abstain from the conception process during the study (i.e., must&#xD;
             agree not to participate in an active attempt to become pregnant or impregnate, donate&#xD;
             sperm, or participate in in vitro fertilization)&#xD;
&#xD;
          -  Unwillingness to use one (for males) or two (for females) reliable methods of&#xD;
             contraception while engaging in heterosexual intercourse during the study. Acceptable&#xD;
             methods for women include hormonal contraception (estrogen/progesterone or&#xD;
             progesterone-only formulations) if stable for a year or more prior to study entry,&#xD;
             intrauterine device, or barrier methods (condom, or diaphragm with spermicide).&#xD;
             Acceptable methods for males include condom use. This requirement does not apply to&#xD;
             women who have been post-menopausal for at least 24 consecutive months or have&#xD;
             undergone surgical sterilization, or to men who have undergone surgical sterilization&#xD;
             or have documented azoospermia.&#xD;
&#xD;
          -  Not willing or able to adhere to dose schedules and required procedures per protocol&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Steven K Grinspoon, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>MGH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institutes of Health</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Stanley TL, Fourman LT, Feldpausch MN, Purdy J, Zheng I, Pan CS, Aepfelbacher J, Buckless C, Tsao A, Kellogg A, Branch K, Lee H, Liu CY, Corey KE, Chung RT, Torriani M, Kleiner DE, Hadigan CM, Grinspoon SK. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. Lancet HIV. 2019 Dec;6(12):e821-e830. doi: 10.1016/S2352-3018(19)30338-8. Epub 2019 Oct 11.</citation>
    <PMID>31611038</PMID>
  </results_reference>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>July 18, 2014</study_first_submitted>
  <study_first_submitted_qc>July 21, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 22, 2014</study_first_posted>
  <results_first_submitted>November 22, 2019</results_first_submitted>
  <results_first_submitted_qc>December 19, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">January 13, 2020</results_first_posted>
  <last_update_submitted>January 13, 2020</last_update_submitted>
  <last_update_submitted_qc>January 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 27, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Steven K. Grinspoon, MD</investigator_full_name>
    <investigator_title>Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>Human immunodeficiency virus (HIV)</keyword>
  <keyword>Nonalcoholic fatty liver disease (NAFLD)</keyword>
  <keyword>Nonalcoholic steatohepatitis (NASH)</keyword>
  <keyword>Growth hormone releasing hormone</keyword>
  <keyword>tesamorelin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acquired Immunodeficiency Syndrome</mesh_term>
    <mesh_term>HIV Infections</mesh_term>
    <mesh_term>Liver Diseases</mesh_term>
    <mesh_term>Fatty Liver</mesh_term>
    <mesh_term>Non-alcoholic Fatty Liver Disease</mesh_term>
    <mesh_term>Immunologic Deficiency Syndromes</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tesamorelin</mesh_term>
  </intervention_browse>
  <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>June 17, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/31/NCT02196831/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>1 subject was randomized to tesamorelin but self-discontinued during the baseline visit, prior to receiving any study drug. This individual is included in baseline characteristics but is not counted as starting tesamorelin (hence the discrepancy between 61 total enrolled and the 30 in tesamorelin and 30 in placebo group shown in participant flow).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Tesamorelin</title>
          <description>tesamorelin 2mg subcutaneously daily x 12 months double-blind phase. At the end of 12 months, subjects enter open-label tesamorelin treatment phase for 6 months.&#xD;
tesamorelin</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>placebo subcutaneously daily x 12 months double-blind phase. At the end of 12 months, subjects enter open-label tesamorelin treatment phase for 6 months.&#xD;
Placebo: inactive substance that looks like tesamorelin</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received Follow-up Imaging</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="26"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All randomized patients. One patient in the tesamorelin group discontinued before receiving study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>Tesamorelin</title>
          <description>tesamorelin 2mg subcutaneously daily x 12 months double-blind phase. At the end of 12 months, subjects enter open-label tesamorelin treatment phase for 6 months.&#xD;
tesamorelin</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>placebo subcutaneously daily x 12 months double-blind phase. At the end of 12 months, subjects enter open-label tesamorelin treatment phase for 6 months.&#xD;
Placebo: inactive substance that looks like tesamorelin</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="31"/>
            <count group_id="B2" value="30"/>
            <count group_id="B3" value="61"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="52" spread="8"/>
                    <measurement group_id="B2" value="54" spread="7"/>
                    <measurement group_id="B3" value="53" spread="7"/>
                  </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="24"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="48"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Race</title>
              <category_list>
                <category>
                  <title>White (all ethnicities)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black (all ethnicities)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other (all ethnicities)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Hepatic Fibrosis Stage</title>
          <description>Fibrosis Stage is determined through standardized histological grading by pathologists; this measure is used routinely in evaluation of patients with liver disease. Stage 1 is the mildest fibrosis, and Stage 4 represents cirrhosis. Those unfamiliar can find a review of this staging system in Kleiner DE and Brunt EM, Nonalcoholic Fatty Liver Disease: Pathologic Patterns and Biopsy Evaluation in Clinical Research, 2012, Semin Liver Dis, 32:003-013.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Stage 0 (No Fibrosis)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Stage 1 Fibrosis</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Stage 2 Fibrosis</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Stage 3 Fibrosis</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Data Not Available</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Liver Fat as Measured by 1-H Magnetic Resonance Spectroscopy</title>
        <description>change (value at 12 months minus value at baseline). Hepatic fat fraction is a standardized measure used to describe the percent fat in the liver. As it is determined by spectroscopy, it is quantified by the area under the lipid peak, standardized to the total area under the (lipid peak + water peak). Using 1-H Magnetic resonance spectroscopy to quantify liver fat in this manner was first described by Longo R et al., Invest Radiol, 1993, 28(4):297-302.</description>
        <time_frame>change between baseline and 12 months</time_frame>
        <population>These are participants who had magnetic resonance spectroscopy for hepatic fat fraction at 0 and 12 months. This is different from the primary analysis population reported in the manuscript.</population>
        <group_list>
          <group group_id="O1">
            <title>Tesamorelin</title>
            <description>tesamorelin 2mg subcutaneously daily x 12 months double-blind phase. At the end of 12 months, subjects enter open-label tesamorelin treatment phase for 6 months.&#xD;
tesamorelin</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>placebo subcutaneously daily x 12 months double-blind phase. At the end of 12 months, subjects enter open-label tesamorelin treatment phase for 6 months.&#xD;
Placebo: inactive substance that looks like tesamorelin</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Liver Fat as Measured by 1-H Magnetic Resonance Spectroscopy</title>
          <description>change (value at 12 months minus value at baseline). Hepatic fat fraction is a standardized measure used to describe the percent fat in the liver. As it is determined by spectroscopy, it is quantified by the area under the lipid peak, standardized to the total area under the (lipid peak + water peak). Using 1-H Magnetic resonance spectroscopy to quantify liver fat in this manner was first described by Longo R et al., Invest Radiol, 1993, 28(4):297-302.</description>
          <population>These are participants who had magnetic resonance spectroscopy for hepatic fat fraction at 0 and 12 months. This is different from the primary analysis population reported in the manuscript.</population>
          <units>percent (hepatic fat fraction)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.7" spread="6.6"/>
                    <measurement group_id="O2" value="0.0" spread="4.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score</title>
        <description>change (value at 12 months minus value at baseline). The nonalcoholic fatty liver disease (NAFLD) activity score is a standardized histological quantification of NAFLD severity designed and validated by the Nonalcoholic Steatohepatitis Clinical Research Network (Kleiner DE et al., Hepatology, 2005, 41(6):1313-1321). The score is the sum of three semi-quantitative histological grades:&#xD;
steatosis, graded from 0 [&lt;5% liver fat] to grade 3 [&gt;66% liver fat]&#xD;
lobular inflammation, graded from 0 [no foci of inflammation] to 3 [&gt;4 foci per 200x field]&#xD;
hepatocellular ballooning, graded from 0 [no ballooning] to 2 [many cells/prominent ballooning] The &quot;total&quot; NAFLD activity score, a sum of the three components below, ranges from 0 to 8, with a higher score generally representing greater severity of NAFLD/nonalcoholic steatohepatitis.</description>
        <time_frame>change between baseline and 12 months</time_frame>
        <population>all participants with available biopsy data from both baseline and 12 month visits</population>
        <group_list>
          <group group_id="O1">
            <title>Tesamorelin</title>
            <description>tesamorelin 2mg subcutaneously daily x 12 months double-blind phase. At the end of 12 months, subjects enter open-label tesamorelin treatment phase for 6 months.&#xD;
tesamorelin</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>placebo subcutaneously daily x 12 months double-blind phase. At the end of 12 months, subjects enter open-label tesamorelin treatment phase for 6 months.&#xD;
Placebo: inactive substance that looks like tesamorelin</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score</title>
          <description>change (value at 12 months minus value at baseline). The nonalcoholic fatty liver disease (NAFLD) activity score is a standardized histological quantification of NAFLD severity designed and validated by the Nonalcoholic Steatohepatitis Clinical Research Network (Kleiner DE et al., Hepatology, 2005, 41(6):1313-1321). The score is the sum of three semi-quantitative histological grades:&#xD;
steatosis, graded from 0 [&lt;5% liver fat] to grade 3 [&gt;66% liver fat]&#xD;
lobular inflammation, graded from 0 [no foci of inflammation] to 3 [&gt;4 foci per 200x field]&#xD;
hepatocellular ballooning, graded from 0 [no ballooning] to 2 [many cells/prominent ballooning] The &quot;total&quot; NAFLD activity score, a sum of the three components below, ranges from 0 to 8, with a higher score generally representing greater severity of NAFLD/nonalcoholic steatohepatitis.</description>
          <population>all participants with available biopsy data from both baseline and 12 month visits</population>
          <units>score on a scale, NAFLD activity score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.16" spread="1.34"/>
                    <measurement group_id="O2" value="0.13" spread="1.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Alanine Aminotransferase (ALT)</title>
        <description>change (value at 12 months minus value at baseline)</description>
        <time_frame>change from baseline to 12 months</time_frame>
        <population>all participants with available data at both baseline and 12 month visits</population>
        <group_list>
          <group group_id="O1">
            <title>Tesamorelin</title>
            <description>tesamorelin 2mg subcutaneously daily x 12 months double-blind phase. At the end of 12 months, subjects enter open-label tesamorelin treatment phase for 6 months.&#xD;
tesamorelin</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>placebo subcutaneously daily x 12 months double-blind phase. At the end of 12 months, subjects enter open-label tesamorelin treatment phase for 6 months.&#xD;
Placebo: inactive substance that looks like tesamorelin</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Alanine Aminotransferase (ALT)</title>
          <description>change (value at 12 months minus value at baseline)</description>
          <population>all participants with available data at both baseline and 12 month visits</population>
          <units>units/liter (U/L)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2" spread="11"/>
                    <measurement group_id="O2" value="5" spread="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Aspartate Aminotransferase (AST)</title>
        <description>change (value at 12 months minus value at baseline)</description>
        <time_frame>change from baseline to 12 months</time_frame>
        <population>all participants with available data at both baseline and 12 month visits</population>
        <group_list>
          <group group_id="O1">
            <title>Tesamorelin</title>
            <description>tesamorelin 2mg subcutaneously daily x 12 months double-blind phase. At the end of 12 months, subjects enter open-label tesamorelin treatment phase for 6 months.&#xD;
tesamorelin</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>placebo subcutaneously daily x 12 months double-blind phase. At the end of 12 months, subjects enter open-label tesamorelin treatment phase for 6 months.&#xD;
Placebo: inactive substance that looks like tesamorelin</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Aspartate Aminotransferase (AST)</title>
          <description>change (value at 12 months minus value at baseline)</description>
          <population>all participants with available data at both baseline and 12 month visits</population>
          <units>units/liter (U/L)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2" spread="11"/>
                    <measurement group_id="O2" value="-2" spread="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events reported herein are from the double-blind (tesamorelin vs. placebo) phase of the study which was 12 months in length as well as the subsequent open-label phase 6 months in length.</time_frame>
      <desc>The primary analysis is from baseline to 12 months, during the &quot;double-blind&quot; phase. Adverse events from this phase are reported under the &quot;Tesamorelin (Double-blind phase)&quot; and &quot;Placebo (Double-blind phase)&quot; descriptors. 43 participants subsequently entered a 6 month open label phase during which all received tesamorelin. Data from this phase are not included in analysis, but Adverse Event data from the Open Label phase are included under the descriptor, &quot;Open Label Tesamorelin Arm.&quot;</desc>
      <group_list>
        <group group_id="E1">
          <title>Tesamorelin (Double-blind Phase)</title>
          <description>tesamorelin 2mg subcutaneously daily x 12 months double-blind phase. At the end of 12 months, subjects enter open-label tesamorelin treatment phase for 6 months.&#xD;
tesamorelin</description>
        </group>
        <group group_id="E2">
          <title>Placebo (Double-blind Phase)</title>
          <description>placebo subcutaneously daily x 12 months double-blind phase. At the end of 12 months, subjects enter open-label tesamorelin treatment phase for 6 months.&#xD;
Placebo: inactive substance that looks like tesamorelin</description>
        </group>
        <group group_id="E3">
          <title>Open Label Tesamorelin Arm</title>
          <description>following the 12 month double-blind period, all subjects received open-label tesamorelin 2mg daily subcutaneously for 6 months.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (10.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <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="31"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death sudden</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic Hematoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Viral infection</sub_title>
                <description>influenza requiring hospitalization</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Soft tissue infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Urosepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Drug overdose</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Hemiplegia transient</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety Depression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Suicide attempt</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Active suicidal ideation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>4.9</frequency_threshold>
        <default_vocab>MedDRA (10.0)</default_vocab>
        <default_assessment>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="29" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="35" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Injection site bruising</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Injection site induration</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Injection site itching</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Injection site pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Injection site redness</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Injection site stinging</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Tooth Infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>URTI (upper respiratory tract infection)</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Viral infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Fracture</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Pain post biopsy</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Fasting blood glucose increased</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="14" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Nonspecific abnormal findings on radiological and other examinations</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyper LDL cholesterolemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Hypercholesterolemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>Steven Grinspoon, MD</name_or_title>
      <organization>Massachusetts General Hospital</organization>
      <phone>617-724-9109</phone>
      <email>sgrinspoon@mgh.harvard.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/NCT02196831
org study id: 1U01AI115711
secondary id: U01AI115711
nct id: NCT02196831
lead sponsor: 
collaborator: 
has dmc: Yes
Liver disease is one of the leading co-morbidities of human immunodeficiency virus (HIV)
      infection, and nonalcoholic fatty liver disease (NAFLD) is present in approximately 30-40% of
      patients with HIV infection. Nonalcoholic steatohepatitis (NASH) is a more severe form of
      NAFLD in which increased liver fat is also accompanied by inflammation, cellular damage, and
      fibrosis.

      NAFLD is most prevalent in patients who also have increased visceral adiposity, and our group
      has previously shown that HIV-infected individuals with increased visceral adiposity
      generally have decreased growth hormone secretion. Tesamorelin is a growth hormone releasing
      hormone (GHRH) analogue that increases endogenous growth hormone secretion. Tesamorelin is
      FDA-approved for the reduction of visceral fat in HIV-infected individuals. In a previous
      study, treatment with tesamorelin in HIV-infected individuals selected for abdominal
      adiposity reduced liver fat. The current study is designed to test the effect of tesamorelin
      on liver fat and steatohepatitis in HIV-infected individuals who have NAFLD. The
      investigators hypothesize that tesamorelin will reduce liver fat and will also ameliorate the
      inflammation, fibrosis, and hepatocellular damage seen in conjunction with NASH.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in Liver Fat as Measured by 1-H Magnetic Resonance Spectroscopy
time frame: change between baseline and 12 months
description: change (value at 12 months minus value at baseline). Hepatic fat fraction is a standardized measure used to describe the percent fat in the liver. As it is determined by spectroscopy, it is quantified by the area under the lipid peak, standardized to the total area under the (lipid peak + water peak). Using 1-H Magnetic resonance spectroscopy to quantify liver fat in this manner was first described by Longo R et al., Invest Radiol, 1993, 28(4):297-302.
measure: Change in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score
time frame: change between baseline and 12 months
description: change (value at 12 months minus value at baseline). The nonalcoholic fatty liver disease (NAFLD) activity score is a standardized histological quantification of NAFLD severity designed and validated by the Nonalcoholic Steatohepatitis Clinical Research Network (Kleiner DE et al., Hepatology, 2005, 41(6):1313-1321). The score is the sum of three semi-quantitative histological grades:
steatosis, graded from 0 [<5% liver fat] to grade 3 [>66% liver fat]
lobular inflammation, graded from 0 [no foci of inflammation] to 3 [>4 foci per 200x field]
hepatocellular ballooning, graded from 0 [no ballooning] to 2 [many cells/prominent ballooning] The "total" NAFLD activity score, a sum of the three components below, ranges from 0 to 8, with a higher score generally representing greater severity of NAFLD/nonalcoholic steatohepatitis.
measure: Change in Alanine Aminotransferase (ALT)
time frame: change from baseline to 12 months
description: change (value at 12 months minus value at baseline)
measure: Change in Aspartate Aminotransferase (AST)
time frame: change from baseline to 12 months
description: change (value at 12 months minus value at baseline)
arm group label: Tesamorelin
arm group type: Experimental
description: tesamorelin 2mg subcutaneously daily x 12 months double-blind phase. At the end of 12 months, subjects enter open-label tesamorelin treatment phase for 6 months.
arm group label: Placebo
arm group type: Placebo Comparator
description: placebo subcutaneously daily x 12 months double-blind phase. At the end of 12 months, subjects enter open-label tesamorelin treatment phase for 6 months.
intervention type: Drug
intervention name: tesamorelin
arm group label: Tesamorelin
other name: Egrifta
intervention type: Drug
intervention name: Placebo
description: inactive substance that looks like tesamorelin
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Steven K Grinspoon, MD
role: Principal Investigator
affiliation: MGH
facility: 
facility: 
country: United States
citation: Stanley TL, Fourman LT, Feldpausch MN, Purdy J, Zheng I, Pan CS, Aepfelbacher J, Buckless C, Tsao A, Kellogg A, Branch K, Lee H, Liu CY, Corey KE, Chung RT, Torriani M, Kleiner DE, Hadigan CM, Grinspoon SK. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. Lancet HIV. 2019 Dec;6(12):e821-e830. doi: 10.1016/S2352-3018(19)30338-8. Epub 2019 Oct 11.
PMID: 31611038
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Steven K. Grinspoon, MD
investigator title: Professor of Medicine
mesh term: Acquired Immunodeficiency Syndrome
mesh term: HIV Infections
mesh term: Liver Diseases
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease
mesh term: Immunologic Deficiency Syndromes
mesh term: Tesamorelin
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 