xml: <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/NCT06007560</url>
    </required_header>
    <id_info>
      <org_study_id>HMOVE</org_study_id>
      <nct_id>NCT06007560</nct_id>
    </id_info>
    <brief_title>Aerobe Cycling Training in Women With Unexplained Recurrent Pregnancy Loss</brief_title>
    <acronym>HMOVE</acronym>
    <official_title>Aerobe Cycling Training in Women With Unexplained Recurrent Pregnancy Loss</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Radboud University Medical Center</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Maastricht University Medical Center</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Radboud University Medical Center</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>
    </oversight_info>
    <brief_summary>
      <textblock>
        In 50% of women with recurrent pregnancy loss (RPL) miscarriages are unexplained, therefore&#xD;
        no therapeutic intervention is possible. In a pilot study, women with unexplained RPL showed&#xD;
        less endometrial NK cells (eNK) compared to women with a previously uncomplicated pregnancy.&#xD;
        It is known that eNK cells are important for embryo implantation during early pregnancy.&#xD;
        Investigators presume that high sympathetic activity in these women is related to eNK cell&#xD;
        number, function and phenotype and that exercise is an effective intervention to lower&#xD;
        sympathetic activity and to influence the immune system, as especially peripheral NK cells&#xD;
        have been assumed to be responsive to physical training. The investigators hypothesize that&#xD;
        moderate exercise can lower the adrenergic tone of the sympathetic nervous system hereby&#xD;
        influencing endometrial NK cells in women with RPL and eventually pregnancy outcome.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">March 21, 2022</start_date>
    <completion_date type="Anticipated">August 2024</completion_date>
    <primary_completion_date type="Anticipated">August 2024</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>CD56 endometrial NK cell frequency</measure>
      <time_frame>3 months</time_frame>
      <description>Change in CD56 eNK cell frequency measured as percentage of total lymphocyte or total CD56 population by flowcytometry.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>CD56 endometrial NK cell function</measure>
      <time_frame>3 months</time_frame>
      <description>Change in CD56 eNK cell function measured as percentage of CD56 degranulation by flowcytometry.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>CD56 endometrial NK cell phenotype</measure>
      <time_frame>3 months</time_frame>
      <description>Change in CD56 eNK cell phenotype measured as percentage of (sub)population or mean fluorescent intensity respectively by flowcytometry.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>CD56 peripheral NK cell frequency</measure>
      <time_frame>3 months</time_frame>
      <description>Change in CD56 pNK cell frequency measured as percentage of total lymphocyte or CD56 population by flowcytometry.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>CD56 peripheral NK cell function</measure>
      <time_frame>3 months</time_frame>
      <description>Change in CD56 pNK cell function measured as percentage of CD56 degranulation by flowcytometry.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>CD56 peripheral NK cell phenotype</measure>
      <time_frame>3 months</time_frame>
      <description>Change in CD56 pNK cell phenotype measured as percentage of (sub)population or mean fluorescent intensity respectively by flowcytometry.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Vaginal microbiome</measure>
      <time_frame>3 months</time_frame>
      <description>Change in taxonomic classification of vaginal microbiota of different subtypes but also classified in clustering of different subtypes.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Metabolic syndrome parameters I</measure>
      <time_frame>3 months</time_frame>
      <description>Change in cm waist circumference.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Metabolic syndrome parameters II</measure>
      <time_frame>3 months</time_frame>
      <description>Chance in mmHg blood pressure, both systolic as diastolic.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Metabolic syndrome parameters III</measure>
      <time_frame>3 months</time_frame>
      <description>Change in concentration (mg/dL) triglyceride.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Metabolic syndrome parameters IV</measure>
      <time_frame>3 months</time_frame>
      <description>Change in concentration (mg/dL) cholesterol levels.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Metabolic syndrome parameters V</measure>
      <time_frame>3 months</time_frame>
      <description>Change in concentration (mg/dL) blood sugar levels.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Sympathetic activity</measure>
      <time_frame>3 months</time_frame>
      <description>Change in baroreceptor sensitivity in ms/mmHg.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Uterine blood flow</measure>
      <time_frame>3 months</time_frame>
      <description>Change in pulsatility index, lower indicates better outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Physical fitness</measure>
      <time_frame>3 months</time_frame>
      <description>Change in VO2max.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pregnancy rate and live birth rate after one year of intervention, higher rater indicate better outcome.</measure>
      <time_frame>3 months</time_frame>
      <description>Questionnaire.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Recurrent Pregnancy Loss</condition>
    <arm_group>
      <arm_group_label>&lt;80% eNK</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Women with low eNK bright cell numbers, defined as &lt;80% of the total endometrial NK cell population</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Exercise</intervention_name>
      <description>Aerobe cycling training consisting of 12-weeks of HR-controlled training at 50-60% of VO2max (maximal oxygen uptake) for 1 hour, for 2 times (week: 1-6) to 3 times (week: 7-12) per week</description>
      <arm_group_label>&lt;80% eNK</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  RPL defined as 2 or more unexplained pregnancy losses from the time of conception&#xD;
               until 24 weeks of gestation, known cause for the miscarriages are the presence of&#xD;
               thyroid abnormalities, anti-phospholipid syndrome, uterine malformation, and abnormal&#xD;
               parental karyotype according to international guideline.&#xD;
  &#xD;
            -  Couples should not be aiming to conceive during the time course of the exercise&#xD;
               intervention.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Age above 40 years&#xD;
  &#xD;
            -  BMI above 40&#xD;
  &#xD;
            -  Current use of immunosuppressive or biological drugs&#xD;
  &#xD;
            -  Current use of hormone conceptive&#xD;
  &#xD;
            -  HIV positivity&#xD;
  &#xD;
            -  Current or recent (&lt;2 weeks) symptomatic genital infection such as chlamydia,&#xD;
               gonorroa, or pelvic inflammatory disease&#xD;
  &#xD;
            -  Pre-existent diabetes mellitus, autoimmune disease or overt cardiovascular disease&#xD;
  &#xD;
            -  Vaccination (i.e Covid) within 1 month prior to or during sampling and intervention&#xD;
  &#xD;
            -  New pregnancy at time of measurements, breastfeeding&#xD;
  &#xD;
            -  Current or recent (&lt;2-3 months ago) pregnancy&#xD;
  &#xD;
            -  (Physical) inabilities to follow moderate aerobe cycling training&#xD;
  &#xD;
            -  Participants who are not capable of signing the informed consent&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <minimum_age>N/A</minimum_age>
      <maximum_age>40 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Tess Meuleman</last_name>
      <role>Principal Investigator</role>
      <affiliation>Radboud University Medical Center</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Tess Meuleman, Dr. MD.</last_name>
      <phone>0031-631133392</phone>
      <email>tess.meuleman@radboudumc.nl</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Denise Habets, Dr.</last_name>
      <phone>0031-623385664</phone>
      <email>denise.habets@mumc.nl</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Maastricht UMC+</name>
        <address>
          <city>Maastricht</city>
          <zip>6202 AZ</zip>
          <country>Netherlands</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Denise Habets, Dr.</last_name>
        <phone>0031-623385664</phone>
        <email>denise.habets@mumc.nl</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Radboud UMC</name>
        <address>
          <city>Nijmegen</city>
          <zip>6500 HB</zip>
          <country>Netherlands</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Tess Meuleman, Dr. MD.</last_name>
        <phone>0031-631133392</phone>
        <email>tess.meuleman@radboudumc.nl</email>
      </contact>
    </location>
    <location_countries>
      <country>Netherlands</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>November 29, 2022</study_first_submitted>
    <study_first_submitted_qc>August 22, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 23, 2023</study_first_posted>
    <last_update_submitted>August 22, 2023</last_update_submitted>
    <last_update_submitted_qc>August 22, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 23, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Radboud University Medical Center</investigator_affiliation>
      <investigator_full_name>Tess Meuleman</investigator_full_name>
      <investigator_title>Principal Investigator</investigator_title>
    </responsible_party>
    <keyword>Natural Killer cells</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Abortion, Spontaneous</mesh_term>
      <mesh_term>Fetal Death</mesh_term>
      <mesh_term>Abortion, Habitual</mesh_term>
      <mesh_term>Recurrence</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>On reasonable special request only.</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06007560
  org study id: HMOVE
  nct id: NCT06007560
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  In 50% of women with recurrent pregnancy loss (RPL) miscarriages are unexplained, therefore
        no therapeutic intervention is possible. In a pilot study, women with unexplained RPL showed
        less endometrial NK cells (eNK) compared to women with a previously uncomplicated pregnancy.
        It is known that eNK cells are important for embryo implantation during early pregnancy.
        Investigators presume that high sympathetic activity in these women is related to eNK cell
        number, function and phenotype and that exercise is an effective intervention to lower
        sympathetic activity and to influence the immune system, as especially peripheral NK cells
        have been assumed to be responsive to physical training. The investigators hypothesize that
        moderate exercise can lower the adrenergic tone of the sympathetic nervous system hereby
        influencing endometrial NK cells in women with RPL and eventually pregnancy outcome.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Basic Science
  masking: None (Open Label)
  measure: CD56 endometrial NK cell frequency
  time frame: 3 months
  description: Change in CD56 eNK cell frequency measured as percentage of total lymphocyte or total CD56 population by flowcytometry.
  measure: CD56 endometrial NK cell function
  time frame: 3 months
  description: Change in CD56 eNK cell function measured as percentage of CD56 degranulation by flowcytometry.
  measure: CD56 endometrial NK cell phenotype
  time frame: 3 months
  description: Change in CD56 eNK cell phenotype measured as percentage of (sub)population or mean fluorescent intensity respectively by flowcytometry.
  measure: CD56 peripheral NK cell frequency
  time frame: 3 months
  description: Change in CD56 pNK cell frequency measured as percentage of total lymphocyte or CD56 population by flowcytometry.
  measure: CD56 peripheral NK cell function
  time frame: 3 months
  description: Change in CD56 pNK cell function measured as percentage of CD56 degranulation by flowcytometry.
  measure: CD56 peripheral NK cell phenotype
  time frame: 3 months
  description: Change in CD56 pNK cell phenotype measured as percentage of (sub)population or mean fluorescent intensity respectively by flowcytometry.
  measure: Vaginal microbiome
  time frame: 3 months
  description: Change in taxonomic classification of vaginal microbiota of different subtypes but also classified in clustering of different subtypes.
  measure: Metabolic syndrome parameters I
  time frame: 3 months
  description: Change in cm waist circumference.
  measure: Metabolic syndrome parameters II
  time frame: 3 months
  description: Chance in mmHg blood pressure, both systolic as diastolic.
  measure: Metabolic syndrome parameters III
  time frame: 3 months
  description: Change in concentration (mg/dL) triglyceride.
  measure: Metabolic syndrome parameters IV
  time frame: 3 months
  description: Change in concentration (mg/dL) cholesterol levels.
  measure: Metabolic syndrome parameters V
  time frame: 3 months
  description: Change in concentration (mg/dL) blood sugar levels.
  measure: Sympathetic activity
  time frame: 3 months
  description: Change in baroreceptor sensitivity in ms/mmHg.
  measure: Uterine blood flow
  time frame: 3 months
  description: Change in pulsatility index, lower indicates better outcome.
  measure: Physical fitness
  time frame: 3 months
  description: Change in VO2max.
  measure: Pregnancy rate and live birth rate after one year of intervention, higher rater indicate better outcome.
  time frame: 3 months
  description: Questionnaire.
  arm group label: <80% eNK
  arm group type: Other
  description: Women with low eNK bright cell numbers, defined as <80% of the total endometrial NK cell population
  intervention type: Other
  intervention name: Exercise
  description: Aerobe cycling training consisting of 12-weeks of HR-controlled training at 50-60% of VO2max (maximal oxygen uptake) for 1 hour, for 2 times (week: 1-6) to 3 times (week: 7-12) per week
  arm group label: <80% eNK
  criteria: 
  gender: Female
  minimum age: N/A
  maximum age: 40 Years
  healthy volunteers: No
  last name: Tess Meuleman
  role: Principal Investigator
  affiliation: Radboud University Medical Center
  last name: Tess Meuleman, Dr. MD.
  phone: 0031-631133392
  email: tess.meuleman@radboudumc.nl
  last name: Denise Habets, Dr.
  phone: 0031-623385664
  email: denise.habets@mumc.nl
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  country: Netherlands
  responsible party type: Principal Investigator
  investigator affiliation: Radboud University Medical Center
  investigator full name: Tess Meuleman
  investigator title: Principal Investigator
  mesh term: Abortion, Spontaneous
  mesh term: Fetal Death
  mesh term: Abortion, Habitual
  mesh term: Recurrence
  sharing ipd: No
  ipd description: On reasonable special request only.