<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/NCT03292146</url>
  </required_header>
  <id_info>
    <org_study_id>2017P000529</org_study_id>
    <nct_id>NCT03292146</nct_id>
  </id_info>
  <brief_title>Effects of Denosumab on Bone Mineral Density in Women With Anorexia Nervosa: A Pilot Study</brief_title>
  <official_title>Effects of Denosumab on Bone Mineral Density, Markers of Bone Metabolism and Bone Microarchitecture in Women With Anorexia Nervosa: A Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Amgen</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </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>
      This protocol is a randomized, double-blind, placebo-controlled clinical trial which aims to&#xD;
      investigate the effect of denosumab on BMD in women with anorexia nervosa. The investigators&#xD;
      hypothesize that 12 months of denosumab administration will result in an increase in bone&#xD;
      mineral density, decrease in markers of bone resorption and improvement in bone&#xD;
      microarchitecture in osteopenic women with anorexia nervosa compared with placebo.&#xD;
&#xD;
      An optional extension study will offer subjects 12-month administration of open-label&#xD;
      alendronate (an oral bisphosphonate) after the initial 12 month administration of denosumab&#xD;
      or placebo. We hypothesize that 12 months of denosumab followed by 12 months of open-label&#xD;
      alendronate will result in a greater increase in BMD compared to 12 months of placebo&#xD;
      followed by 12 months of open-label alendronate. Within the group of women who receive&#xD;
      sequential therapy with 12 months of denosumab followed by 12 months of alendronate, we&#xD;
      hypothesize that BMD will be maintained between 12 and 24 months while on alendronate.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 25, 2017</start_date>
  <completion_date type="Actual">July 22, 2021</completion_date>
  <primary_completion_date type="Actual">July 22, 2021</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>Double blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Postero-anterior (PA) Lumbar Spine Bone Mineral Density by Dual-energy X-ray Absorptiometry (DXA)</measure>
    <time_frame>12 months (Period 1)</time_frame>
    <description>Postero-anterior (PA) lumbar spine bone mineral density was assessed by dual-energy x-ray absorptiometry (DXA). The DXA scanner used was a Hologic Horizon A (Hologic, Inc., Waltham, MA).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent Change Postero-anterior (PA) Lumbar Spine Bone Mineral Density by DXA</measure>
    <time_frame>Baseline to 24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change Postero-anterior (PA) Lumbar Spine Bone Mineral Density by DXA</measure>
    <time_frame>12 months to 24 months (Period 2)</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Bone Density</condition>
  <condition>Bone Loss</condition>
  <condition>Anorexia Nervosa</condition>
  <condition>Eating Disorder</condition>
  <condition>Atypical Anorexia Nervosa</condition>
  <arm_group>
    <arm_group_label>Active Denosumab 60mg Injection</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Denosumab 60mg injection at baseline study visit and 6 month study visit. Alendronate 70mg PO weekly starting at Month 12 through 24 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo injection at baseline study visit and 6 month study visit. Alendronate 70mg PO weekly starting at Month 12 through 24 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Denosumab 60 MG [Prolia]</intervention_name>
    <description>Denosumab 60mg injection at baseline and 6 months</description>
    <arm_group_label>Active Denosumab 60mg Injection</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Injection</intervention_name>
    <description>Placebo Injection at baseline and 6 months</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alendronate 70Mg Tab</intervention_name>
    <description>Alendronate 70mg PO weekly starting at Month 12 through 24 months.</description>
    <arm_group_label>Active Denosumab 60mg Injection</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion/Exclusion Criteria:&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Female&#xD;
&#xD;
          -  Age 20-60 years, skeletally mature with closed epiphyses&#xD;
&#xD;
          -  Anorexia nervosa or atypical anorexia nervosa defined by DSM-V diagnostic criteria&#xD;
&#xD;
          -  BMD T-score &lt; -1.0&#xD;
&#xD;
          -  Normal serum 25-OH vitamin D (&gt;30 ng/mL) and calcium levels&#xD;
&#xD;
          -  For women of reproductive age, agree to use an effective contraceptive method. Highly&#xD;
             effective methods of birth control include:&#xD;
&#xD;
               -  Combined (estrogen and progestogen) hormonal methods (pills, vaginal ring, or&#xD;
                  skin patch)&#xD;
&#xD;
               -  Intrauterine device (IUD)&#xD;
&#xD;
               -  Intraduterine hormonal-releasing system (IUS)&#xD;
&#xD;
               -  Surgery to tie both fallopian tubes (bilateral tubal ligation/occlusion)&#xD;
&#xD;
               -  Your male partner has had a vasectomy and testing shows there is no sperm in the&#xD;
                  semen&#xD;
&#xD;
          -  Dental check up within the past year&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any disease known to affect bone, including untreated thyroid dysfunction, Cushing's&#xD;
             or renal failure&#xD;
&#xD;
          -  Subjects with a known esophageal disease cannot participate in the alendronate&#xD;
             extension study&#xD;
&#xD;
          -  Any medication known to affect bone metabolism within 3 months of the study, excluding&#xD;
             oral contraceptives or other forms of estrogen administration. Bisphosphonates must&#xD;
             have been discontinued for at least one year before participation&#xD;
&#xD;
          -  Immunodeficiency or taking immunosuppressive therapy&#xD;
&#xD;
          -  Serum potassium &lt;3.0 meq/L&#xD;
&#xD;
          -  Serum ALT &gt;3 times upper limit of normal&#xD;
&#xD;
          -  eGFR of less than 30 ml/min&#xD;
&#xD;
          -  Hypocalcemia&#xD;
&#xD;
          -  Diabetes mellitus&#xD;
&#xD;
          -  Active substance abuse, including alcohol&#xD;
&#xD;
          -  History of malignancy&#xD;
&#xD;
          -  Paget disease of bone&#xD;
&#xD;
          -  Osteomalacia&#xD;
&#xD;
          -  Osteonecrosis of the jaw (ONJ) or risk factor for ONJ, such as invasive dental&#xD;
             procedures (eg, tooth extraction, dental implants, oral surgery in the past 6 months),&#xD;
             poor oral hygiene, periodontal and/or pre-existing dental disease, and current use of&#xD;
             corticosteroids.&#xD;
&#xD;
          -  Planned invasive dental procedure over the next 24 months.&#xD;
&#xD;
          -  Known senstivity to any of the products or components to be administered during dosing&#xD;
             or known sensitivity to mammalian cell derived drug products&#xD;
&#xD;
          -  Sensitivity to calcium or vitamin D supplements&#xD;
&#xD;
          -  Pregnant, planning to become pregnant with 7 months after the end of treatment and/or&#xD;
             breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>60 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>September 2022</verification_date>
  <study_first_submitted>September 21, 2017</study_first_submitted>
  <study_first_submitted_qc>September 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <results_first_submitted>July 20, 2022</results_first_submitted>
  <results_first_submitted_qc>September 19, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">October 12, 2022</results_first_posted>
  <last_update_submitted>September 19, 2022</last_update_submitted>
  <last_update_submitted_qc>September 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 12, 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>Professor of Medicine</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anorexia</mesh_term>
    <mesh_term>Feeding and Eating Disorders</mesh_term>
    <mesh_term>Anorexia Nervosa</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Denosumab</mesh_term>
    <mesh_term>Alendronate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <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>March 2, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/46/NCT03292146/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>July 13, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/46/NCT03292146/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Women, age 20-60 years, with anorexia nervosa or atypical anorexia nervosa and BMD T-score &lt; -1.0</recruitment_details>
      <pre_assignment_details>Randomized, double-blind, placebo-controlled trial. 30 subjects randomized in a 2:1 ratio to denosumab followed by alendronate or placebo followed by alendronate groups</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Denosumab (0-12 Months) Followed by Alendronate (12-24 Months)</title>
          <description>Denosumab 60 mg SQ injections q6 months for 12 months followed by alendronate 70 mg PO weekly for 12 months.</description>
        </group>
        <group group_id="P2">
          <title>Placebo (0-12 Months) Followed by Alendronate (12-24 Months)</title>
          <description>Placebo SQ injections q6 months for 12 months followed by alendronate 70 mg PO weekly for 12 months.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Baseline to 12 Months</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Relocation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Seeking higher level of care for eating disorder</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Seeking treatment for chronic fatigue syndrome</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>
          <title>12 Months to 24 Months</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Planning pregnancy</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Personal reasons</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</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>Women, age 20-60 years, with anorexia nervosa or atypical anorexia nervosa and BMD T-score &lt; -1.0</population>
      <group_list>
        <group group_id="B1">
          <title>Denosumab (0-12 Months) Followed by Alendronate (12-24 Months)</title>
          <description>Denosumab 60 mg SQ injections q6 months for 12 months followed by alendronate 70 mg PO weekly for 12 months.</description>
        </group>
        <group group_id="B2">
          <title>Placebo (0-12 Months) Followed by Alendronate (12-24 Months)</title>
          <description>Placebo SQ injections q6 months for 12 months followed by alendronate 70 mg PO weekly for 12 months</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="20"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="30"/>
          </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="20"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>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="29.2" spread="8.0"/>
                    <measurement group_id="B2" value="29.4" spread="6.8"/>
                    <measurement group_id="B3" value="29.3" spread="7.5"/>
                  </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="20"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</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>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="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="30"/>
                  </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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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>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>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="20"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body mass index (BMI)</title>
          <units>kg / m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19.0" spread="1.7"/>
                    <measurement group_id="B2" value="18.0" spread="2.0"/>
                    <measurement group_id="B3" value="18.7" spread="1.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Postero-anterior (PA) lumbar spine areal bone mineral density (aBMD) Z-score</title>
          <description>PA lumbar spine aBMD Z-score was obtained by dual-energy x-ray absorptiometry (DXA). A BMD Z-score is the number of standard deviations above or below the mean BMD given a person's age, sex, and race. A BMD Z-score of &quot;0&quot; represents the population mean. A BMD Z-score &gt;0 represents a higher/better BMD, whereas a BMD Z-score &lt;0 represents a lower/worse BMD. A BMD Z-score between -1 and -2.5 signifies osteopenia. A BMD Z-score at or below -2.5 signifies osteoporosis.</description>
          <units>Z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="-1.6" spread="0.9"/>
                    <measurement group_id="B2" value="-1.7" spread="1.4"/>
                    <measurement group_id="B3" value="-1.6" spread="1.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Postero-anterior (PA) lumbar spine aBMD</title>
          <units>g/cm^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0.86" spread="0.09"/>
                    <measurement group_id="B2" value="0.85" spread="0.16"/>
                    <measurement group_id="B3" value="0.86" spread="0.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Postero-anterior (PA) Lumbar Spine Bone Mineral Density by Dual-energy X-ray Absorptiometry (DXA)</title>
        <description>Postero-anterior (PA) lumbar spine bone mineral density was assessed by dual-energy x-ray absorptiometry (DXA). The DXA scanner used was a Hologic Horizon A (Hologic, Inc., Waltham, MA).</description>
        <time_frame>12 months (Period 1)</time_frame>
        <population>Women, age 20-60 years, with anorexia nervosa or atypical anorexia nervosa and BMD T-score &lt; -1.0</population>
        <group_list>
          <group group_id="O1">
            <title>Denosumab (0-12 Months) Followed by Alendronate (12-24 Months)</title>
            <description>Denosumab 60 mg SQ injections q6 months for 12 months followed by alendronate 70 mg PO weekly for 12 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo (0-12 Months) Followed by Alendronate (12-24 Months)</title>
            <description>Placebo SQ injections q6 months for 12 months followed by alendronate 70 mg PO weekly for 12 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Postero-anterior (PA) Lumbar Spine Bone Mineral Density by Dual-energy X-ray Absorptiometry (DXA)</title>
          <description>Postero-anterior (PA) lumbar spine bone mineral density was assessed by dual-energy x-ray absorptiometry (DXA). The DXA scanner used was a Hologic Horizon A (Hologic, Inc., Waltham, MA).</description>
          <population>Women, age 20-60 years, with anorexia nervosa or atypical anorexia nervosa and BMD T-score &lt; -1.0</population>
          <units>g/cm^2</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.90" spread="0.03"/>
                    <measurement group_id="O2" value="0.87" spread="0.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.009</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change Postero-anterior (PA) Lumbar Spine Bone Mineral Density by DXA</title>
        <time_frame>Baseline to 24 months</time_frame>
        <population>Women ages 20-60 with anorexia nervosa/atypical anorexia nervosa and BMD T-score &lt; -1.0</population>
        <group_list>
          <group group_id="O1">
            <title>Denosumab (0-12 Months) Followed by Alendronate (12-24 Months)</title>
            <description>Denosumab 60 mg SQ injections q6 months for 12 months followed by alendronate 70 mg PO weekly for 12 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo (0-12 Months) Followed by Alendronate (12-24 Months)</title>
            <description>Placebo SQ injections q6 months for 12 months followed by alendronate 70 mg PO weekly for 12 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change Postero-anterior (PA) Lumbar Spine Bone Mineral Density by DXA</title>
          <population>Women ages 20-60 with anorexia nervosa/atypical anorexia nervosa and BMD T-score &lt; -1.0</population>
          <units>% change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.9" spread="4.3"/>
                    <measurement group_id="O2" value="5.8" spread="5.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.41</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change Postero-anterior (PA) Lumbar Spine Bone Mineral Density by DXA</title>
        <time_frame>12 months to 24 months (Period 2)</time_frame>
        <population>Women ages 20-60 with anorexia nervosa/atypical anorexia nervosa and BMD T-score &lt; -1.0</population>
        <group_list>
          <group group_id="O1">
            <title>Denosumab (0-12 Months) Followed by Alendronate (12-24 Months)</title>
            <description>Denosumab 60 mg SQ injections q6 months for 12 months followed by alendronate 70 mg PO weekly for 12 months.</description>
          </group>
          <group group_id="O2">
            <title>Placebo (0-12 Months) Followed by Alendronate (12-24 Months)</title>
            <description>Placebo SQ injections q6 months for 12 months followed by alendronate 70 mg PO weekly for 12 months.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change Postero-anterior (PA) Lumbar Spine Bone Mineral Density by DXA</title>
          <population>Women ages 20-60 with anorexia nervosa/atypical anorexia nervosa and BMD T-score &lt; -1.0</population>
          <units>% change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0" spread="3.7"/>
                    <measurement group_id="O2" value="4.6" spread="3.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.06</p_value>
            <method>Matched pairs</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.01</p_value>
            <method>Matched pairs</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline to 24 months</time_frame>
      <desc>Serious adverse events reported to the IRB immediately upon the PI becoming aware.</desc>
      <group_list>
        <group group_id="E1">
          <title>Denosumab (0-12 Months) Followed by Alendronate (12-24 Months)</title>
          <description>Denosumab 60 mg SQ injections q6 months for 12 months followed by alendronate 70 mg PO weekly for 12 months.</description>
        </group>
        <group group_id="E2">
          <title>Placebo (0-12 Months) Followed by Alendronate (12-24 Months)</title>
          <description>Placebo SQ injections q6 months for 12 months followed by alendronate 70 mg PO weekly for 12 months.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>constipation</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>nausea/stomach pain/bloating</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Gallbladder biliary dyskinesia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>COVID-19</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Keratitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>C. difficile</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>bone fracture</sub_title>
                <description>Unrelated injury</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Disc degeneration and herniation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </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 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>Karen K. Miller, MD</name_or_title>
      <organization>Massachusetts General Hospital</organization>
      <phone>617-724-7388</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/NCT03292146
org study id: 2017P000529
nct id: NCT03292146
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This protocol is a randomized, double-blind, placebo-controlled clinical trial which aims to
      investigate the effect of denosumab on BMD in women with anorexia nervosa. The investigators
      hypothesize that 12 months of denosumab administration will result in an increase in bone
      mineral density, decrease in markers of bone resorption and improvement in bone
      microarchitecture in osteopenic women with anorexia nervosa compared with placebo.

      An optional extension study will offer subjects 12-month administration of open-label
      alendronate (an oral bisphosphonate) after the initial 12 month administration of denosumab
      or placebo. We hypothesize that 12 months of denosumab followed by 12 months of open-label
      alendronate will result in a greater increase in BMD compared to 12 months of placebo
      followed by 12 months of open-label alendronate. Within the group of women who receive
      sequential therapy with 12 months of denosumab followed by 12 months of alendronate, we
      hypothesize that BMD will be maintained between 12 and 24 months while on alendronate.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: Double blind
measure: Postero-anterior (PA) Lumbar Spine Bone Mineral Density by Dual-energy X-ray Absorptiometry (DXA)
time frame: 12 months (Period 1)
description: Postero-anterior (PA) lumbar spine bone mineral density was assessed by dual-energy x-ray absorptiometry (DXA). The DXA scanner used was a Hologic Horizon A (Hologic, Inc., Waltham, MA).
measure: Percent Change Postero-anterior (PA) Lumbar Spine Bone Mineral Density by DXA
time frame: Baseline to 24 months
measure: Percent Change Postero-anterior (PA) Lumbar Spine Bone Mineral Density by DXA
time frame: 12 months to 24 months (Period 2)
arm group label: Active Denosumab 60mg Injection
arm group type: Experimental
description: Denosumab 60mg injection at baseline study visit and 6 month study visit. Alendronate 70mg PO weekly starting at Month 12 through 24 months.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo injection at baseline study visit and 6 month study visit. Alendronate 70mg PO weekly starting at Month 12 through 24 months.
intervention type: Drug
intervention name: Denosumab 60 MG [Prolia]
description: Denosumab 60mg injection at baseline and 6 months
arm group label: Active Denosumab 60mg Injection
intervention type: Drug
intervention name: Placebo Injection
description: Placebo Injection at baseline and 6 months
arm group label: Placebo
intervention type: Drug
intervention name: Alendronate 70Mg Tab
description: Alendronate 70mg PO weekly starting at Month 12 through 24 months.
arm group label: Active Denosumab 60mg Injection
arm group label: Placebo
criteria: 
gender: Female
minimum age: 20 Years
maximum age: 60 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: Professor of Medicine
mesh term: Anorexia
mesh term: Feeding and Eating Disorders
mesh term: Anorexia Nervosa
mesh term: Denosumab
mesh term: Alendronate
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 