<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/NCT01690000</url>
  </required_header>
  <id_info>
    <org_study_id>2011-AKA</org_study_id>
    <nct_id>NCT01690000</nct_id>
  </id_info>
  <brief_title>Treatment of Osteopenia With Melatonin</brief_title>
  <acronym>MelaOst</acronym>
  <official_title>Treatment of Osteopenia With Melatonin: Effects on BMD, Muscle Strength and Quality of Life</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Aarhus</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Aarhus</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of the study is to assess the effect of melatonin treatment in patients with&#xD;
      osteopenia on BMD, muscle function, quality of life and calcium homeostasis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background: Melatonin is known for its regulation of circadian rhythm. The production falls&#xD;
      with age, which explains why elderly may have disturbed sleep patterns. Laboratory study and&#xD;
      animal experimental studies suggests that melatonin also may protect against bone loss&#xD;
      through increased osteoblast- and inhibited osteoclast activity. However, so far human&#xD;
      studies have not been performed.&#xD;
&#xD;
      Design and patients: Double blinded randomised controlled study. Eighty post-menopausal women&#xD;
      (aged 55-75) with osteopenia are randomized to receive 1mg, 3mg or placebo (daily - at night&#xD;
      time) for 12 months.&#xD;
&#xD;
      Methods and results: Effects of melatonin on BMD, bone- structure and mass will be assessed&#xD;
      through DXA-scans, pQCT, and QCT. Quality of life, sleep, and activity level will be assessed&#xD;
      though questionnaires. Calcium homeostasis will be analyzed through blood and urines samples.&#xD;
      As safety parameters, balance and muscle function will also be performed.&#xD;
&#xD;
      Conclusion: Expected improvements in BMD, quality of life and sleep.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">June 2014</completion_date>
  <primary_completion_date type="Actual">June 2014</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>Changes in Bone Mineral Density (BMD)</measure>
    <time_frame>baseline and end of study (after 12 months)</time_frame>
    <description>Effects of melatonin on BMD will be assessed through DXA-scans</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in Calcium Homeostasis</measure>
    <time_frame>baseline, after 3, 6, 9 months, and end of study (after 12 months)</time_frame>
    <description>Calcium homeostasis will be analyzed through blood and urines samples</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">81</enrollment>
  <condition>Osteoporosis</condition>
  <arm_group>
    <arm_group_label>Melatonin1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>1 mg melatonin nightly</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Melatonin3</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>3 mg melatonin given nightly</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Identical placebo given nightly</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Melatonin</intervention_name>
    <description>1 or 3 mg of melatonin PO each night for 12 months</description>
    <arm_group_label>Melatonin1</arm_group_label>
    <arm_group_label>Melatonin3</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Postmenopausal women between 55 and 75 years.&#xD;
&#xD;
          -  Osteopenia verified by DXA-scans of total hip or lumbar spine (t-score between -1 and&#xD;
             -2.5)&#xD;
&#xD;
          -  Written informed consent after oral and written information&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severely impaired renal function (plasma creatinine &gt;60 eGFR ml/l).&#xD;
&#xD;
          -  Severely impaired hepatic function (Plasma alanine aminotransferase (ALAT) and/or&#xD;
             alkaline phosphatase more the doubled compared to upper limit of reference value).&#xD;
&#xD;
          -  Coagulation factors PP &lt;0.6&#xD;
&#xD;
          -  Hypercalcemia (p-ion calcium &gt; 1.32 nmol/l)&#xD;
&#xD;
          -  Previous or present malignancies (except a treated skin cancer that is not melanoma or&#xD;
             treated carcinoma in situ, 2 years since last therapy).&#xD;
&#xD;
          -  Diseases affecting the calcium homeostasis including untreated thyroid diseases.&#xD;
&#xD;
          -  Regular use of medicine affecting the calcium homeostasis; including diuretics,&#xD;
             lithium, antiepileptica, glucosteroids.&#xD;
&#xD;
          -  SSRI-product with fluvoxamin.&#xD;
&#xD;
          -  Treatment with carbamazepin&#xD;
&#xD;
          -  Treatment with rifampicin&#xD;
&#xD;
          -  Severe malabsorption syndrome including gastric or intestinal resection.&#xD;
&#xD;
          -  Alcohol or drug abuse.&#xD;
&#xD;
          -  Smokers&#xD;
&#xD;
          -  Major medical or social problems that will be likely to preclude participation for one&#xD;
             year.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anne Kristine Amstrup, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Osteoporoseklinikken, Dept. of Endocrinology and Internal Medicine (MEA) Aarhus University Hospital, Tage-Hansens Gade 2, AArhus, DEnmark</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Osteoporoseklinikken, dept of Endocrinology and Internal Medicine (MEA)</name>
      <address>
        <city>Aarhus C</city>
        <zip>8000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>April 2013</verification_date>
  <study_first_submitted>June 28, 2012</study_first_submitted>
  <study_first_submitted_qc>September 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 21, 2012</study_first_posted>
  <results_first_submitted>February 1, 2016</results_first_submitted>
  <results_first_submitted_qc>March 31, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">May 6, 2016</results_first_posted>
  <last_update_submitted>March 31, 2016</last_update_submitted>
  <last_update_submitted_qc>March 31, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 6, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoporosis</mesh_term>
    <mesh_term>Bone Diseases, Metabolic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melatonin</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>We recruited 81 postmenopausal women with osteopenia to receive either melatonin (n=40) (1 or 3 mg) or similar placebo (n=41) nightly for 12 months. In addition, all women received a daily supplementation with 800mg calcium and 20ug D3</recruitment_details>
      <pre_assignment_details>A total of 202 women were invited to participate. 81 were included in the study</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Melatonin1+3</title>
          <description>Melatonin: 1 or 3 mg of melatonin PO each night for 12 months</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Identical placebo given nightly for 12 months</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="40"/>
                <participants group_id="P2" count="41"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="37"/>
                <participants group_id="P2" count="35"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Melatonin1+3</title>
          <description>Melatonin: 1 or 3 mg of melatonin PO each night for 12 months</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Identical placebo given nightly 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="40"/>
            <count group_id="B2" value="41"/>
            <count group_id="B3" value="81"/>
          </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="32"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="61"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="20"/>
                  </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="40"/>
                    <measurement group_id="B2" value="41"/>
                    <measurement group_id="B3" value="81"/>
                  </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>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Denmark</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                    <measurement group_id="B2" value="41"/>
                    <measurement group_id="B3" value="81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Changes in Bone Mineral Density (BMD)</title>
        <description>Effects of melatonin on BMD will be assessed through DXA-scans</description>
        <time_frame>baseline and end of study (after 12 months)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Melatonin1+3</title>
            <description>1+3 mg melatonin nightly&#xD;
Melatonin: 1 or 3 mg of melatonin PO each night for 12 months</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Identical placebo given nightly&#xD;
Melatonin: 1 or 3 mg of melatonin PO each night for 12 months</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in Bone Mineral Density (BMD)</title>
          <description>Effects of melatonin on BMD will be assessed through DXA-scans</description>
          <units>percentage of change in BMD</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.05" spread="3.07"/>
                    <measurement group_id="O2" value="-1.45" spread="2.81"/>
                  </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>
            <groups_desc>The p-value was calculated</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <p_value_desc>The p-value was calculated</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes in Calcium Homeostasis</title>
        <description>Calcium homeostasis will be analyzed through blood and urines samples</description>
        <time_frame>baseline, after 3, 6, 9 months, and end of study (after 12 months)</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>12 months (entire study period)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Melatonin1+3</title>
          <description>Melatonin: 1 or 3 mg of melatonin PO each night for 12 months</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Identical placebo given nightly for 12 months</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Planned operation</sub_title>
                <description>Pre-planned operation of known musculoskeletal or cardiac complaints not related to the study.</description>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="40"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="40"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infection not assumed related to study medicine</sub_title>
                <counts group_id="E1" events="22" subjects_affected="19" subjects_at_risk="40"/>
                <counts group_id="E2" events="21" subjects_affected="17" subjects_at_risk="41"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Anne Kristine Amstrup</name_or_title>
      <organization>Aarhus University</organization>
      <phone>4578467681</phone>
      <email>anne_kristine_am@hotmail.com</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/NCT01690000
org study id: 2011-AKA
nct id: NCT01690000
lead sponsor: 
has dmc: Yes
The aim of the study is to assess the effect of melatonin treatment in patients with
      osteopenia on BMD, muscle function, quality of life and calcium homeostasis.
Background: Melatonin is known for its regulation of circadian rhythm. The production falls
      with age, which explains why elderly may have disturbed sleep patterns. Laboratory study and
      animal experimental studies suggests that melatonin also may protect against bone loss
      through increased osteoblast- and inhibited osteoclast activity. However, so far human
      studies have not been performed.

      Design and patients: Double blinded randomised controlled study. Eighty post-menopausal women
      (aged 55-75) with osteopenia are randomized to receive 1mg, 3mg or placebo (daily - at night
      time) for 12 months.

      Methods and results: Effects of melatonin on BMD, bone- structure and mass will be assessed
      through DXA-scans, pQCT, and QCT. Quality of life, sleep, and activity level will be assessed
      though questionnaires. Calcium homeostasis will be analyzed through blood and urines samples.
      As safety parameters, balance and muscle function will also be performed.

      Conclusion: Expected improvements in BMD, quality of life and sleep.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Changes in Bone Mineral Density (BMD)
time frame: baseline and end of study (after 12 months)
description: Effects of melatonin on BMD will be assessed through DXA-scans
measure: Changes in Calcium Homeostasis
time frame: baseline, after 3, 6, 9 months, and end of study (after 12 months)
description: Calcium homeostasis will be analyzed through blood and urines samples
arm group label: Melatonin1
arm group type: Active Comparator
description: 1 mg melatonin nightly
arm group label: Melatonin3
arm group type: Active Comparator
description: 3 mg melatonin given nightly
arm group label: Placebo
arm group type: Active Comparator
description: Identical placebo given nightly
intervention type: Drug
intervention name: Melatonin
description: 1 or 3 mg of melatonin PO each night for 12 months
arm group label: Melatonin1
arm group label: Melatonin3
arm group label: Placebo
criteria: 
gender: Female
minimum age: 55 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Anne Kristine Amstrup, MD
role: Principal Investigator
affiliation: Osteoporoseklinikken, Dept. of Endocrinology and Internal Medicine (MEA) Aarhus University Hospital, Tage-Hansens Gade 2, AArhus, DEnmark
facility: 
country: Denmark
responsible party type: Sponsor
mesh term: Osteoporosis
mesh term: Bone Diseases, Metabolic
mesh term: Melatonin
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 