<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/NCT03782740</url>
  </required_header>
  <id_info>
    <org_study_id>Mel PP</org_study_id>
    <nct_id>NCT03782740</nct_id>
  </id_info>
  <brief_title>Effect of Melatonin on Reduction of Pelvic Pain</brief_title>
  <official_title>Effect of Melatonin on Reduction of Pelvic Pain</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Karolinska Institutet</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Karolinska Institutet</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      In two double blinded randomized controlled trials (RCT) we will study the effect of pain&#xD;
      reduction of melatonin vs placebo in women with severe dysmenorrhea and women with&#xD;
      endometriosis.The aim is to find an effective method for pelvic pain caused by dysmenorrhea&#xD;
      and endometriosis.The primary outcome is reduction of pain in patients with dysmenorrhea and&#xD;
      endometriosis respectively when treated with melatonin vs placebo. Secondary outcomes include&#xD;
      the effect on daily life, quality of life and cognition. Sleep will also be assessed to&#xD;
      evaluate its potential relation to quality of life and cognition.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Two substudies will be performed. Forty women with severe dysmenorrhea will be randomized to&#xD;
      treatment with 10 mg melatonin daily or placebo during the menstruation for 2 menstrual&#xD;
      cycles. Another 40 women with endometriosis will be randomized to treatment with 20 mg or&#xD;
      placebo daily during 8 weeks. Participants will report drug intake, bleeding details&#xD;
      (duration and amount) and pain as well as possible side effects. They will also perform a&#xD;
      test for sleep quality and cognition before and after completion of the study.&#xD;
&#xD;
      See protocol for more details&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 15, 2019</start_date>
  <completion_date type="Actual">June 30, 2021</completion_date>
  <primary_completion_date type="Actual">June 27, 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>
    <intervention_model_description>Two parallel studies (dysmenorrhea and endometriosis) with 40 participants in each.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pain reduction</measure>
    <time_frame>12 weeks</time_frame>
    <description>Self reported pain intensity daily, Numeric Rating Scale (NRS) 0-10 (0=no pain, 10 = worst possible pain)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Use of analgesics</measure>
    <time_frame>12 weeks</time_frame>
    <description>Self reported daily quantification of intake of analgesics reported online</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of sleep</measure>
    <time_frame>12 weeks</time_frame>
    <description>Insomnia Severity index questionnaire will be administered during observational cycle and once during the second treatment cycle. 0 to 28 Points, 0-7 Points signifies no Clinical significant sleeping dificulties, 22-28 Points signifies Clinical insomnia)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognition</measure>
    <time_frame>12 weeks</time_frame>
    <description>Dysmenorrhea group: Online test (CANTAB) performed on day 1-4 in the menstrual cycle in the observational cycle and in the second treatment cycle.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Catastrophic thinking</measure>
    <time_frame>12 weeks</time_frame>
    <description>Endometriosis group: Pain Catastrophizing Scale questionnaire will be administered during observational cycle and once during the second treatment cycle. 0-52 Points, higher points indicate higher tendency to catastrophize.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>General well being</measure>
    <time_frame>12 weeks</time_frame>
    <description>Endometriosis group: Quality of life assessment with Endometriosis Health Profile (EHP-30) will be administered during observational cycle and once during the second treatment cycle. Score 0-100 Points, where 0 is best health status and 100 is worst health status.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acceptance of Melatonin</measure>
    <time_frame>12 weeks</time_frame>
    <description>Assessment at the end of study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Side effects of Melatonin</measure>
    <time_frame>12 weeks</time_frame>
    <description>Online self reporting, daily</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">80</enrollment>
  <condition>Dysmenorrhea</condition>
  <condition>Endometriosis</condition>
  <arm_group>
    <arm_group_label>Dysmenorrhea Melatonin 10 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In the dysmenorrhea group: 2 capsules with 5 mg melatonin will be given in the evening for seven days consecutively during menstruation for two mentrual cycles. Compared with placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Endometriosis Melatonin 20 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In the endometriosis group: 4 capsules with 5 mg melatonin will be given every evening during eight weeks. Compared with placebo.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Melatonin 10 mg</intervention_name>
    <description>Melatonin capsule</description>
    <arm_group_label>Dysmenorrhea Melatonin 10 mg</arm_group_label>
    <other_name>N-acetyl-5-methoxy tryptamine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Sugar pill manufactured to mimic Melatonin capsule</description>
    <arm_group_label>Dysmenorrhea Melatonin 10 mg</arm_group_label>
    <arm_group_label>Endometriosis Melatonin 20 mg</arm_group_label>
    <other_name>Sugar pill</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Melatonin 20 mg</intervention_name>
    <description>Melatonin capsule</description>
    <arm_group_label>Endometriosis Melatonin 20 mg</arm_group_label>
    <other_name>N-acetyl-5-methoxy tryptamine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Dysmenorrhea group&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Regular menstrual cycles,&#xD;
&#xD;
          -  Severe dysmenorrhea (NRS&gt;6)&#xD;
&#xD;
          -  Speaks and understands Swedish&#xD;
&#xD;
          -  If other medication, those should be un-altered for the last 3 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Smoker&#xD;
&#xD;
          -  Prior or ongoing liver or kidney disease&#xD;
&#xD;
          -  Endometriosis&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
        Endometriosis group:&#xD;
&#xD;
        Criteria for inclusion:&#xD;
&#xD;
          -  Endometriosis (endometriomas or diagnosis by laparoscopy)&#xD;
&#xD;
          -  Moderate to severe pain (NRS &gt;/= 4)&#xD;
&#xD;
          -  Good general health&#xD;
&#xD;
          -  Understands and speaks Swedish&#xD;
&#xD;
          -  If any other treatment, unchanged regimen for the last 3 months&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Criteria for exclusion:&#xD;
&#xD;
          -  Prior or ongoing disease in kidney or liver&#xD;
&#xD;
          -  Use of opioid analgesics&#xD;
&#xD;
          -  Smoker&#xD;
&#xD;
          -  Pregnant&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Södersjukhuset</name>
      <address>
        <city>Stockholm</city>
        <zip>118 32</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>November 14, 2018</study_first_submitted>
  <study_first_submitted_qc>December 19, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 20, 2018</study_first_posted>
  <last_update_submitted>April 4, 2022</last_update_submitted>
  <last_update_submitted_qc>April 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 5, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Karolinska Institutet</investigator_affiliation>
    <investigator_full_name>Lena Marions</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Endometriosis</mesh_term>
    <mesh_term>Pelvic Pain</mesh_term>
    <mesh_term>Dysmenorrhea</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melatonin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03782740
org study id: Mel PP
nct id: NCT03782740
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
In two double blinded randomized controlled trials (RCT) we will study the effect of pain
      reduction of melatonin vs placebo in women with severe dysmenorrhea and women with
      endometriosis.The aim is to find an effective method for pelvic pain caused by dysmenorrhea
      and endometriosis.The primary outcome is reduction of pain in patients with dysmenorrhea and
      endometriosis respectively when treated with melatonin vs placebo. Secondary outcomes include
      the effect on daily life, quality of life and cognition. Sleep will also be assessed to
      evaluate its potential relation to quality of life and cognition.
Two substudies will be performed. Forty women with severe dysmenorrhea will be randomized to
      treatment with 10 mg melatonin daily or placebo during the menstruation for 2 menstrual
      cycles. Another 40 women with endometriosis will be randomized to treatment with 20 mg or
      placebo daily during 8 weeks. Participants will report drug intake, bleeding details
      (duration and amount) and pain as well as possible side effects. They will also perform a
      test for sleep quality and cognition before and after completion of the study.

      See protocol for more details
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Two parallel studies (dysmenorrhea and endometriosis) with 40 participants in each.
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Pain reduction
time frame: 12 weeks
description: Self reported pain intensity daily, Numeric Rating Scale (NRS) 0-10 (0=no pain, 10 = worst possible pain)
measure: Use of analgesics
time frame: 12 weeks
description: Self reported daily quantification of intake of analgesics reported online
measure: Quality of sleep
time frame: 12 weeks
description: Insomnia Severity index questionnaire will be administered during observational cycle and once during the second treatment cycle. 0 to 28 Points, 0-7 Points signifies no Clinical significant sleeping dificulties, 22-28 Points signifies Clinical insomnia)
measure: Cognition
time frame: 12 weeks
description: Dysmenorrhea group: Online test (CANTAB) performed on day 1-4 in the menstrual cycle in the observational cycle and in the second treatment cycle.
measure: Catastrophic thinking
time frame: 12 weeks
description: Endometriosis group: Pain Catastrophizing Scale questionnaire will be administered during observational cycle and once during the second treatment cycle. 0-52 Points, higher points indicate higher tendency to catastrophize.
measure: General well being
time frame: 12 weeks
description: Endometriosis group: Quality of life assessment with Endometriosis Health Profile (EHP-30) will be administered during observational cycle and once during the second treatment cycle. Score 0-100 Points, where 0 is best health status and 100 is worst health status.
measure: Acceptance of Melatonin
time frame: 12 weeks
description: Assessment at the end of study
measure: Side effects of Melatonin
time frame: 12 weeks
description: Online self reporting, daily
arm group label: Dysmenorrhea Melatonin 10 mg
arm group type: Experimental
description: In the dysmenorrhea group: 2 capsules with 5 mg melatonin will be given in the evening for seven days consecutively during menstruation for two mentrual cycles. Compared with placebo.
arm group label: Endometriosis Melatonin 20 mg
arm group type: Experimental
description: In the endometriosis group: 4 capsules with 5 mg melatonin will be given every evening during eight weeks. Compared with placebo.
intervention type: Drug
intervention name: Melatonin 10 mg
description: Melatonin capsule
arm group label: Dysmenorrhea Melatonin 10 mg
other name: N-acetyl-5-methoxy tryptamine
intervention type: Drug
intervention name: Placebo
description: Sugar pill manufactured to mimic Melatonin capsule
arm group label: Dysmenorrhea Melatonin 10 mg
arm group label: Endometriosis Melatonin 20 mg
other name: Sugar pill
intervention type: Drug
intervention name: Melatonin 20 mg
description: Melatonin capsule
arm group label: Endometriosis Melatonin 20 mg
other name: N-acetyl-5-methoxy tryptamine
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
facility: 
country: Sweden
responsible party type: Principal Investigator
investigator affiliation: Karolinska Institutet
investigator full name: Lena Marions
investigator title: Associate Professor
mesh term: Endometriosis
mesh term: Pelvic Pain
mesh term: Dysmenorrhea
mesh term: Melatonin