<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/NCT02217345</url>
  </required_header>
  <id_info>
    <org_study_id>2014P001680</org_study_id>
    <nct_id>NCT02217345</nct_id>
  </id_info>
  <brief_title>Growth Hormone and Intrahepatic Lipid Content in Patients With Nonalcoholic Fatty Liver Disease</brief_title>
  <acronym>NAFLD</acronym>
  <official_title>Growth Hormone and Intrahepatic Lipid Content in Patients With Nonalcoholic Fatty Liver Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Nonalcoholic fatty liver disease (NAFLD), fatty infiltration of the liver in the absence of&#xD;
      alcohol use, is an increasingly recognized complication of obesity, with prevalence estimates&#xD;
      of about 30% of individuals in the United States. A subset of these will develop progressive&#xD;
      disease in the form of nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis&#xD;
      and liver failure. NAFLD is expected to be the most common indication for liver&#xD;
      transplantation by the year 2020. We hypothesize that growth hormone (GH) replacement will&#xD;
      decrease intrahepatic lipid accumulation as quantified by 1H magnetic resonance spectroscopy&#xD;
      (1H-MRS).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 2, 2017</start_date>
  <completion_date type="Actual">September 13, 2021</completion_date>
  <primary_completion_date type="Actual">August 10, 2021</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Intrahepatic Lipid Content Between Baseline and 6 Months as Measured by 1H-magnetic Resonance Spectroscopy (1H-MRS). Endpoints Were Assessed at Baseline and 6 Months.</measure>
    <time_frame>6 months</time_frame>
    <description>Change in Intrahepatic lipid content by 1H-MRS over 6 months in the GH vs placebo group</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Serum High Sensitivity C-reactive Protein (hsCRP) Between Baseline and 6 Months.</measure>
    <time_frame>6 months</time_frame>
    <description>Change in serum high sensitivity C-reactive protein (hsCRP) (mg/L) between baseline and 6 months.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">131</enrollment>
  <condition>Nonalcoholic Fatty Liver Disease (NAFLD)</condition>
  <arm_group>
    <arm_group_label>Growth hormone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Growth hormone (somatropin) administered by daily injection at starting dose of 0.3 mg daily for women and 0.2 mg daily for men, with dose titration for goal IGF-1 in the upper quartile of normal for age.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo will be administered by daily injection in this double blind study design. Sham dosing will be performed to maintain blinding.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Growth hormone</intervention_name>
    <description>growth hormone, Genotropin (Pfizer)</description>
    <arm_group_label>Growth hormone</arm_group_label>
    <other_name>Genotropin (Pfizer Inc.)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>placebo with identical drug pen delivery device and packaging as Genotropin (Pfizer)</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Ages 18 - 65 yr&#xD;
&#xD;
          2. NAFLD defined as demonstration of hepatic steatosis by imaging or biopsy in absence of&#xD;
             significant alcohol consumption and other causes of hepatic steatosis. If liver&#xD;
             imaging or biopsy has not been performed clinically, liver ultrasound will be&#xD;
             performed as part of the screening visit.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Serum creatinine &gt; 2 times the upper limit of normal&#xD;
&#xD;
          2. History of cancer, except for non-melanoma skin cancers&#xD;
&#xD;
          3. Active carpel tunnel syndrome&#xD;
&#xD;
          4. Diabetes mellitus, defined as a hemoglobin A1C &gt;6.5 or use of any medications&#xD;
             prescribed to treat hyperglycemia. The exception is that the use of metformin is&#xD;
             acceptable in patients whose HbA1c has been =&lt;6.0 on two visits and whose weight has&#xD;
             remained stable for six months.&#xD;
&#xD;
          5. Contraindications to magnetic resonance imaging (MRI).&#xD;
&#xD;
          6. Pregnancy or desire to become pregnant. Participants of reproductive age must agree to&#xD;
             use contraception.&#xD;
&#xD;
          7. Breastfeeding&#xD;
&#xD;
          8. Aspartate and aminotransferase levels &gt;10x upper limit of normal&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Karen K Miller, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <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>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>July 15, 2014</study_first_submitted>
  <study_first_submitted_qc>August 13, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 15, 2014</study_first_posted>
  <results_first_submitted>September 13, 2022</results_first_submitted>
  <results_first_submitted_qc>October 28, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">November 22, 2022</results_first_posted>
  <last_update_submitted>October 28, 2022</last_update_submitted>
  <last_update_submitted_qc>October 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 22, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Karen Klahr Miller, MD</investigator_full_name>
    <investigator_title>Neuroendocrine Unit Chief</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hormones</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 17, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/45/NCT02217345/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 17, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/45/NCT02217345/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Subjects were recruited through hospital-wide and community advertisements between 2017-2021. Recruitment techniques included posting advertisements on the internet (i.e. Craigslist and Facebook) and on the Massachusetts General Hospital's clinical trial recruitment website.</recruitment_details>
      <pre_assignment_details>Of the 131 people who signed a consent form, 78 were unable to participate due to various reasons including meeting ineligibility criteria. The 53 subjects who remained were randomized to one of two arms. One subject discontinued after randomization but before any baseline procedures were completed, leaving 52 subjects with available baseline data.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Growth Hormone</title>
          <description>Growth Hormone (GH) is Genotropin, provided by Pfizer Inc. It is a self-administered sub-cutaneous daily injection using an injection pen device. It was administered for 6 months. The dose was titrated based on IGF-1 hormone levels with the goal of maintaining an IGF-1 level in the upper-quartile of the normal range.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo was provided by Pfizer Inc. It appeared identical to active growth hormone and was administered in the same manner; self-administered sub-cutaneous daily for 6 months using an injection pen device. Dose was titrated in a way to maintain the double-blind.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
                <participants group_id="P2" count="26"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Baseline Data Available</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="26"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="5"/>
              </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="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>One subject discontinued after randomization but before any baseline procedures were completed, leaving 52 subjects with available baseline data.</population>
      <group_list>
        <group group_id="B1">
          <title>Growth Hormone</title>
          <description>Growth Hormone (GH) is Genotropin, provided by Pfizer Inc. It is a self-administered sub-cutaneous daily injection using an injection pen device. It was administered for 6 months. The dose was titrated based on IGF-1 hormone levels with the goal of maintaining an IGF-1 level in the upper-quartile of the normal range.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo was provided by Pfizer Inc. It appeared identical to active growth hormone and was administered in the same manner; self-administered sub-cutaneous daily for 6 months using an injection pen device. Dose was titrated in a way to maintain the double-blind.</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="26"/>
            <count group_id="B2" value="26"/>
            <count group_id="B3" value="52"/>
          </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="51"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="46" spread="12"/>
                    <measurement group_id="B2" value="46" spread="12"/>
                    <measurement group_id="B3" value="46" spread="12"/>
                  </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="13"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="50"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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>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="5"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="7"/>
                  </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="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="39"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </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="26"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Intrahepatic Lipid Content Between Baseline and 6 Months as Measured by 1H-magnetic Resonance Spectroscopy (1H-MRS). Endpoints Were Assessed at Baseline and 6 Months.</title>
        <description>Change in Intrahepatic lipid content by 1H-MRS over 6 months in the GH vs placebo group</description>
        <time_frame>6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Growth Hormone</title>
            <description>Growth Hormone (GH) is Genotropin, provided by Pfizer Inc. It is a self-administered sub-cutaneous daily injection using an injection pen device. It was administered for 6 months. The dose was titrated based on IGF-1 hormone levels with the goal of maintaining an IGF-1 level in the upper-quartile of the normal range.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo was provided by Pfizer Inc. It appeared identical to active growth hormone and was administered in the same manner; self-administered sub-cutaneous daily for 6 months using an injection pen device. Dose was titrated in a way to maintain the double-blind.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Intrahepatic Lipid Content Between Baseline and 6 Months as Measured by 1H-magnetic Resonance Spectroscopy (1H-MRS). Endpoints Were Assessed at Baseline and 6 Months.</title>
          <description>Change in Intrahepatic lipid content by 1H-MRS over 6 months in the GH vs placebo group</description>
          <units>percent liver fat</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="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.2" spread="10.5"/>
                    <measurement group_id="O2" value="3.8" spread="6.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Serum High Sensitivity C-reactive Protein (hsCRP) Between Baseline and 6 Months.</title>
        <description>Change in serum high sensitivity C-reactive protein (hsCRP) (mg/L) between baseline and 6 months.</description>
        <time_frame>6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Growth Hormone</title>
            <description>Growth Hormone (GH) is Genotropin, provided by Pfizer Inc. It is a self-administered sub-cutaneous daily injection using an injection pen device. It was administered for 6 months. The dose was titrated based on IGF-1 hormone levels with the goal of maintaining an IGF-1 level in the upper-quartile of the normal range.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo was provided by Pfizer Inc. It appeared identical to active growth hormone and was administered in the same manner; self-administered sub-cutaneous daily for 6 months using an injection pen device. Dose was titrated in a way to maintain the double-blind.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Serum High Sensitivity C-reactive Protein (hsCRP) Between Baseline and 6 Months.</title>
          <description>Change in serum high sensitivity C-reactive protein (hsCRP) (mg/L) between baseline and 6 months.</description>
          <units>mg/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="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.8" spread="0.9"/>
                    <measurement group_id="O2" value="0.3" spread="1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>6 months</time_frame>
      <desc>GH is FDA approved. Adverse events were defined by the clinicaltrials.gov definitions and categorized as &quot;expected&quot; and &quot;unexpected&quot; based on the medication package insert.&#xD;
GH group: 27 randomized and 3 pre-drug discontinuations = 24 at risk Placebo group: 26 randomized and 1 pre-drug discontinuation = 25 at risk&#xD;
# of events = # of subjects that experienced the side effect at any point during the study.</desc>
      <group_list>
        <group group_id="E1">
          <title>Growth Hormone</title>
          <description>Growth Hormone (GH) is Genotropin, provided by Pfizer Inc. It is a self-administered sub-cutaneous daily injection using an injection pen device. It was administered for 6 months. The dose was titrated based on IGF-1 hormone levels with the goal of maintaining an IGF-1 level in the upper-quartile of the normal range.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo was provided by Pfizer Inc. It appeared identical to active growth hormone and was administered in the same manner; self-administered sub-cutaneous daily for 6 months using an injection pen device. Dose was titrated in a way to maintain the double-blind.</description>
        </group>
      </group_list>
      <serious_events>
        <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="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Unrelated surgical procedure</sub_title>
                <description>unrelated SAE</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="15" subjects_at_risk="24"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Edema</sub_title>
                <description>(swelling) in the hands and/or feet</description>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="24"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic Reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="24"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Carpal Tunnel Syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Joint Pain or Stiffness</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="24"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="25"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Numbness or tingling</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="25"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Injection site discomfort or bruising</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="24"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="25"/>
              </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>
    <limitations_and_caveats>We cannot extrapolate efficacy and safety to patients with diabetes mellitus.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Karen K. Miller</name_or_title>
      <organization>Massachusetts General Hospital</organization>
      <phone>617-726-3870</phone>
      <email>kkmiller@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/NCT02217345
org study id: 2014P001680
nct id: NCT02217345
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Nonalcoholic fatty liver disease (NAFLD), fatty infiltration of the liver in the absence of
      alcohol use, is an increasingly recognized complication of obesity, with prevalence estimates
      of about 30% of individuals in the United States. A subset of these will develop progressive
      disease in the form of nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis
      and liver failure. NAFLD is expected to be the most common indication for liver
      transplantation by the year 2020. We hypothesize that growth hormone (GH) replacement will
      decrease intrahepatic lipid accumulation as quantified by 1H magnetic resonance spectroscopy
      (1H-MRS).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in Intrahepatic Lipid Content Between Baseline and 6 Months as Measured by 1H-magnetic Resonance Spectroscopy (1H-MRS). Endpoints Were Assessed at Baseline and 6 Months.
time frame: 6 months
description: Change in Intrahepatic lipid content by 1H-MRS over 6 months in the GH vs placebo group
measure: Change in Serum High Sensitivity C-reactive Protein (hsCRP) Between Baseline and 6 Months.
time frame: 6 months
description: Change in serum high sensitivity C-reactive protein (hsCRP) (mg/L) between baseline and 6 months.
arm group label: Growth hormone
arm group type: Experimental
description: Growth hormone (somatropin) administered by daily injection at starting dose of 0.3 mg daily for women and 0.2 mg daily for men, with dose titration for goal IGF-1 in the upper quartile of normal for age.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo will be administered by daily injection in this double blind study design. Sham dosing will be performed to maintain blinding.
intervention type: Drug
intervention name: Growth hormone
description: growth hormone, Genotropin (Pfizer)
arm group label: Growth hormone
other name: Genotropin (Pfizer Inc.)
intervention type: Drug
intervention name: Placebo
description: placebo with identical drug pen delivery device and packaging as Genotropin (Pfizer)
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Karen K Miller, MD
role: Principal Investigator
affiliation: Massachusetts General Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Karen Klahr Miller, MD
investigator title: Neuroendocrine Unit Chief
mesh term: Liver Diseases
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease
mesh term: Hormones
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: We cannot extrapolate efficacy and safety to patients with diabetes mellitus.
point of contact: 