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/NCT06041204</url>
    </required_header>
    <id_info>
      <org_study_id>Gyne2021</org_study_id>
      <nct_id>NCT06041204</nct_id>
    </id_info>
    <brief_title>Best Treatment for Women With Both (Polycystic Ovary Syndrome) PCOS and Subclinical Hypothyroidism</brief_title>
    <official_title>Letrozole Alone vs. Letrozole Plus Levothyroxine for Ovulation Induction in Infertile Women With Both (Polycystic Ovary Syndrome) PCOS and Sub-clinical Hypothyroidism.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Muhamed Ahmed Abdelmoaty Muhamed Alhagrasy</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Al-Azhar University</source>
    <oversight_info>
      <has_dmc>No</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>
        The goal of this randomized controlled trial is to compare letrozole alone versus letrozole&#xD;
        plus levothyroxine for ovulation induction in infertile women with both PCOS and subclinical&#xD;
        hypothyroidism. The main questions it aims to answer are:&#xD;
  &#xD;
        Is letrozole plus levothyroxine superior to letrozole alone in achieving ovulation in these&#xD;
        patients? Does combining levothyroxine with letrozole lead to higher pregnancy and live birth&#xD;
        rates compared to letrozole alone?&#xD;
  &#xD;
        Participants will be randomized into two groups:&#xD;
  &#xD;
        Group 1 will receive letrozole only, starting at 2.5 mg daily from day 3 to 7 of the&#xD;
        menstrual cycle. The dose will be increased up to 7.5 mg if no ovulation occurs, for a&#xD;
        maximum treatment period of 6 months or until pregnancy is achieved.&#xD;
  &#xD;
        Group 2 will receive letrozole at the same doses as group 1 plus 25 mcg levothyroxine daily.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">May 6, 2021</start_date>
    <completion_date type="Anticipated">November 30, 2023</completion_date>
    <primary_completion_date type="Anticipated">October 1, 2023</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>Single (Participant)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Pregnancy rate</measure>
      <time_frame>Assessed at the end of each cycle. the cycles are 6. Each cycle is 28 days.</time_frame>
      <description>Biochemical evidence of pregnancy by positive urine or serum β-hCG test.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Live birth rate</measure>
      <time_frame>Through study completion average 1 year.</time_frame>
      <description>The number of deliveries that resulted in a live born baby, documented by hospital delivery records.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Ovulation rate</measure>
      <time_frame>Assessed at the end of each cycle. the cycles are 6. Each cycle is 28 days.</time_frame>
      <description>Evidence of ovulation by ultrasound monitoring of dominant follicle development and serum progesterone level &gt; 3 ng/mL in mid-luteal phase.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Miscarriage rate</measure>
      <time_frame>Through study completion average 1 year.</time_frame>
      <description>Loss of clinical pregnancy before 20 weeks gestation, confirmed by ultrasound or histopathology.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Menstrual regularity</measure>
      <time_frame>Through study completion average 1 year.</time_frame>
      <description>Normal ovulatory menstrual cycles defined as cycle length 21-35 days.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Side effects</measure>
      <time_frame>Through study completion average 1 year.</time_frame>
      <description>Participant reports of adverse effects of letrozole or levothyroxine, graded per standard criteria.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">500</enrollment>
    <condition>PCOS (Polycystic Ovary Syndrome) of Bilateral Ovaries</condition>
    <condition>Subclinical Hypothyroidism</condition>
    <condition>Female Infertility</condition>
    <arm_group>
      <arm_group_label>Letrozole Group</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Participants randomized to letrozole group will take 5mg tablets orally daily for 5 days starting on day 3 of cycle. Dose can be adjusted up to 7.5mg based on ovulation response, maintained for subsequent cycles. Treatment continues for up to 6 ovulatory cycles or until pregnancy occurs. Ovulation assessed by follicular monitoring and progesterone. Compliance monitored by pill counts and diary. Routine antenatal care if pregnant. Adverse effects monitored per guidelines. Participants followed for multiple pregnancies. Tablets taken at same time each day. Maximum treatment period is 6 months.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Letrozole plus levothyroxine</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants randomized to this group will take letrozole tablets at same dose and schedule as letrozole only group. In addition, they will take levothyroxine tablets orally once daily. Levothyroxine dose will start at 25mcg and be titrated based on TSH level, with a target TSH in the normal range. Participants will take levothyroxine at approximately same time each day. Letrozole dosing and schedule as described for other group. Treatment continues for up to 6 ovulatory cycles or until pregnancy occurs. Ovulation assessed by follicular monitoring and progesterone. Compliance monitored by pill counts, TSH levels and diary. Routine antenatal care if pregnant. Adverse effects monitored per guidelines. Participants followed for multiple pregnancies. Maximum treatment period is 6 months.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Letrozole 2.5mg</intervention_name>
      <description>Participants will receive 2.5mg letrozole tablets orally daily for 5 days starting on day 3 of menstrual cycle. The 2.5mg dose will be maintained for at least the first 3 cycles. If no ovulation after 3 cycles, dose cautiously increased up to 7.5mg maximum. Once minimum ovulation dose determined, it will be continued for up to 6 cycles total or until pregnancy occurs. Compliance monitored by pill counts and diary. Ovulation assessed by follicular monitoring and progesterone levels. Routine antenatal care if pregnant. Adverse effects monitored and managed per guidelines. Participants followed for multiple pregnancies. Maximum treatment duration is 6 ovulatory cycles or 6 months. Tablets taken at same time each day.</description>
      <arm_group_label>Letrozole Group</arm_group_label>
      <arm_group_label>Letrozole plus levothyroxine</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Levothyroxine 25 Mcg (0.025 Mg) Oral Tablet</intervention_name>
      <description>Participants will take letrozole at same doses as letrozole only group. Also receive levothyroxine starting at 25mcg orally once daily, titrated by 25mcg every 4 weeks to reach normal TSH, maximum 100mcg daily. Once appropriate dose determined to normalize TSH, it is maintained throughout treatment period. Compliance monitored by pill counts, TSH levels, and diary. Treatment continues for up to 6 ovulatory cycles or until pregnancy, whichever is first, maximum 6 months. Ovulation assessed by monitoring and progesterone. Routine antenatal care if pregnant. Adverse effects monitored and managed per guidelines. Participants followed for multiple pregnancies. Letrozole and levothyroxine taken daily at same time. All other procedures same as letrozole only group.</description>
      <arm_group_label>Letrozole plus levothyroxine</arm_group_label>
      <other_name>levothyroxine 25</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          Age between 20-40 years&#xD;
  &#xD;
          BMI between 18-35 kg/m2&#xD;
  &#xD;
          Meet diagnostic criteria for PCOS based on the Rotterdam consensus criteria and ESHRE/ASRM&#xD;
          modifications (2018):&#xD;
  &#xD;
          Oligo- and/or anovulation Clinical and/or biochemical signs of hyperandrogenism Polycystic&#xD;
          ovaries on ultrasound&#xD;
  &#xD;
          Subclinical hypothyroidism defined as TSH level between 5-10 mIU/L with normal free T4&#xD;
  &#xD;
          Infertility duration ≥ 1 year&#xD;
  &#xD;
          Intact ovaries and uterus, confirmed by physical exam and imaging&#xD;
  &#xD;
          Normal semen analysis in male partner&#xD;
  &#xD;
          No tubal or peritoneal factor contributing to infertility&#xD;
  &#xD;
          Effective contraception if not attempting conception&#xD;
  &#xD;
          Willing and able to provide informed consent&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          Known thyroid disease or on thyroid medications&#xD;
  &#xD;
          Abnormal thyroid function tests other than subclinical hypothyroidism&#xD;
  &#xD;
          Hyperprolactinemia&#xD;
  &#xD;
          Presence of other causes of infertility such as:&#xD;
  &#xD;
          Moderate to severe male factor infertility Bilateral tubal occlusion or peritoneal factors&#xD;
          Stage III-IV endometriosis Ovarian failure or insufficiency (high FSH or low AMH)&#xD;
  &#xD;
          Previous diagnosis of any type of congenital adrenal hyperplasia&#xD;
  &#xD;
          Uncontrolled diabetes (HbA1C &gt;8%)&#xD;
  &#xD;
          History of deep vein thrombosis or thromboembolic events&#xD;
  &#xD;
          Any contraindication to letrozole or levothyroxine&#xD;
  &#xD;
          Previous use of letrozole or levothyroxine in past 6 months&#xD;
  &#xD;
          Current or suspected pregnancy&#xD;
  &#xD;
          Breastfeeding&#xD;
  &#xD;
          Inability to comply with treatment and follow-up procedures&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <gender_based>Yes</gender_based>
      <gender_description>This study will only enroll female participants. Patients must be of reproductive age with intact uteri and ovaries to meet the inclusion criteria.&#xD;
  The study aims to induce ovulation for conception in infertile women with PCOS and subclinical hypothyroidism. As such, only individuals biologically born as females and currently identifying as women will be eligible.&#xD;
  All enrolled participants must have functioning ovaries and intact reproductive organs capable of sustaining a pregnancy. Patients who have undergone surgical sterilization procedures like tubal ligation or hysterectomy will be excluded.&#xD;
  Confirmation of female gender will be through medical history, physical examination, and review of medical records if needed. Pregnancy tests will be done at screening and before each treatment cycle.&#xD;
  The reproductive status, ovaries and uterus will be assessed by medical history, physical examination and imaging like ultrasound when indicated.</gender_description>
      <minimum_age>20 Years</minimum_age>
      <maximum_age>40 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Muhamed Alhagrasy, M.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Al-Azhar University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Muhamed Alhagrasy, M.D.</last_name>
      <phone>01017313413</phone>
      <email>MuhamedAhmed.216@azhar.edu.eg</email>
    </overall_contact>
    <location>
      <facility>
        <name>Al-Hussein University Hospital</name>
        <address>
          <city>Cairo</city>
          <zip>11633</zip>
          <country>Egypt</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Muhamed A Alhagrasy, M.D.</last_name>
        <phone>00201017313413</phone>
        <email>MuhamedAhmed.216@azhar.edu.eg</email>
      </contact>
    </location>
    <location_countries>
      <country>Egypt</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 5, 2023</study_first_submitted>
    <study_first_submitted_qc>September 11, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 18, 2023</study_first_posted>
    <last_update_submitted>September 11, 2023</last_update_submitted>
    <last_update_submitted_qc>September 11, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Al-Azhar University</investigator_affiliation>
      <investigator_full_name>Muhamed Ahmed Abdelmoaty Muhamed Alhagrasy</investigator_full_name>
      <investigator_title>lecturer and consultant at Obstetrics and Gynecology Department.</investigator_title>
    </responsible_party>
    <keyword>Letrozole</keyword>
    <keyword>Levothyroxine</keyword>
    <keyword>PCOS</keyword>
    <keyword>Subclinical hypothyroidism</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Polycystic Ovary Syndrome</mesh_term>
      <mesh_term>Infertility</mesh_term>
      <mesh_term>Infertility, Female</mesh_term>
      <mesh_term>Hypothyroidism</mesh_term>
      <mesh_term>Syndrome</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Letrozole</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>To protect participant confidentiality, individual-level data from this study will not be made publicly available. However, de-identified aggregated data and results can be shared with other researchers upon request after publication. Any data provided will be limited, non-identifiable, and subject to a data use agreement to ensure participant privacy. Only select excerpts needed to validate findings will be shared under approved research objectives. The investigators reserve the right to reject requests that may compromise anonymity. We aim to promote transparency through controlled data access rather than public availability of the full dataset due to re-identification risks for participants.</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/NCT06041204
  org study id: Gyne2021
  nct id: NCT06041204
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this randomized controlled trial is to compare letrozole alone versus letrozole
        plus levothyroxine for ovulation induction in infertile women with both PCOS and subclinical
        hypothyroidism. The main questions it aims to answer are:
  
        Is letrozole plus levothyroxine superior to letrozole alone in achieving ovulation in these
        patients? Does combining levothyroxine with letrozole lead to higher pregnancy and live birth
        rates compared to letrozole alone?
  
        Participants will be randomized into two groups:
  
        Group 1 will receive letrozole only, starting at 2.5 mg daily from day 3 to 7 of the
        menstrual cycle. The dose will be increased up to 7.5 mg if no ovulation occurs, for a
        maximum treatment period of 6 months or until pregnancy is achieved.
  
        Group 2 will receive letrozole at the same doses as group 1 plus 25 mcg levothyroxine daily.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Single (Participant)
  measure: Pregnancy rate
  time frame: Assessed at the end of each cycle. the cycles are 6. Each cycle is 28 days.
  description: Biochemical evidence of pregnancy by positive urine or serum β-hCG test.
  measure: Live birth rate
  time frame: Through study completion average 1 year.
  description: The number of deliveries that resulted in a live born baby, documented by hospital delivery records.
  measure: Ovulation rate
  time frame: Assessed at the end of each cycle. the cycles are 6. Each cycle is 28 days.
  description: Evidence of ovulation by ultrasound monitoring of dominant follicle development and serum progesterone level > 3 ng/mL in mid-luteal phase.
  measure: Miscarriage rate
  time frame: Through study completion average 1 year.
  description: Loss of clinical pregnancy before 20 weeks gestation, confirmed by ultrasound or histopathology.
  measure: Menstrual regularity
  time frame: Through study completion average 1 year.
  description: Normal ovulatory menstrual cycles defined as cycle length 21-35 days.
  measure: Side effects
  time frame: Through study completion average 1 year.
  description: Participant reports of adverse effects of letrozole or levothyroxine, graded per standard criteria.
  arm group label: Letrozole Group
  arm group type: Active Comparator
  description: Participants randomized to letrozole group will take 5mg tablets orally daily for 5 days starting on day 3 of cycle. Dose can be adjusted up to 7.5mg based on ovulation response, maintained for subsequent cycles. Treatment continues for up to 6 ovulatory cycles or until pregnancy occurs. Ovulation assessed by follicular monitoring and progesterone. Compliance monitored by pill counts and diary. Routine antenatal care if pregnant. Adverse effects monitored per guidelines. Participants followed for multiple pregnancies. Tablets taken at same time each day. Maximum treatment period is 6 months.
  arm group label: Letrozole plus levothyroxine
  arm group type: Experimental
  description: Participants randomized to this group will take letrozole tablets at same dose and schedule as letrozole only group. In addition, they will take levothyroxine tablets orally once daily. Levothyroxine dose will start at 25mcg and be titrated based on TSH level, with a target TSH in the normal range. Participants will take levothyroxine at approximately same time each day. Letrozole dosing and schedule as described for other group. Treatment continues for up to 6 ovulatory cycles or until pregnancy occurs. Ovulation assessed by follicular monitoring and progesterone. Compliance monitored by pill counts, TSH levels and diary. Routine antenatal care if pregnant. Adverse effects monitored per guidelines. Participants followed for multiple pregnancies. Maximum treatment period is 6 months.
  intervention type: Drug
  intervention name: Letrozole 2.5mg
  description: Participants will receive 2.5mg letrozole tablets orally daily for 5 days starting on day 3 of menstrual cycle. The 2.5mg dose will be maintained for at least the first 3 cycles. If no ovulation after 3 cycles, dose cautiously increased up to 7.5mg maximum. Once minimum ovulation dose determined, it will be continued for up to 6 cycles total or until pregnancy occurs. Compliance monitored by pill counts and diary. Ovulation assessed by follicular monitoring and progesterone levels. Routine antenatal care if pregnant. Adverse effects monitored and managed per guidelines. Participants followed for multiple pregnancies. Maximum treatment duration is 6 ovulatory cycles or 6 months. Tablets taken at same time each day.
  arm group label: Letrozole Group
  arm group label: Letrozole plus levothyroxine
  intervention type: Drug
  intervention name: Levothyroxine 25 Mcg (0.025 Mg) Oral Tablet
  description: Participants will take letrozole at same doses as letrozole only group. Also receive levothyroxine starting at 25mcg orally once daily, titrated by 25mcg every 4 weeks to reach normal TSH, maximum 100mcg daily. Once appropriate dose determined to normalize TSH, it is maintained throughout treatment period. Compliance monitored by pill counts, TSH levels, and diary. Treatment continues for up to 6 ovulatory cycles or until pregnancy, whichever is first, maximum 6 months. Ovulation assessed by monitoring and progesterone. Routine antenatal care if pregnant. Adverse effects monitored and managed per guidelines. Participants followed for multiple pregnancies. Letrozole and levothyroxine taken daily at same time. All other procedures same as letrozole only group.
  arm group label: Letrozole plus levothyroxine
  other name: levothyroxine 25
  criteria: 
  gender: Female
  gender based: Yes
  gender description: This study will only enroll female participants. Patients must be of reproductive age with intact uteri and ovaries to meet the inclusion criteria.
  The study aims to induce ovulation for conception in infertile women with PCOS and subclinical hypothyroidism. As such, only individuals biologically born as females and currently identifying as women will be eligible.
  All enrolled participants must have functioning ovaries and intact reproductive organs capable of sustaining a pregnancy. Patients who have undergone surgical sterilization procedures like tubal ligation or hysterectomy will be excluded.
  Confirmation of female gender will be through medical history, physical examination, and review of medical records if needed. Pregnancy tests will be done at screening and before each treatment cycle.
  The reproductive status, ovaries and uterus will be assessed by medical history, physical examination and imaging like ultrasound when indicated.
  minimum age: 20 Years
  maximum age: 40 Years
  healthy volunteers: No
  last name: Muhamed Alhagrasy, M.D.
  role: Principal Investigator
  affiliation: Al-Azhar University
  last name: Muhamed Alhagrasy, M.D.
  phone: 01017313413
  email: MuhamedAhmed.216@azhar.edu.eg
  facility: 
  status: Recruiting
  contact: 
  country: Egypt
  responsible party type: Sponsor-Investigator
  investigator affiliation: Al-Azhar University
  investigator full name: Muhamed Ahmed Abdelmoaty Muhamed Alhagrasy
  investigator title: lecturer and consultant at Obstetrics and Gynecology Department.
  mesh term: Polycystic Ovary Syndrome
  mesh term: Infertility
  mesh term: Infertility, Female
  mesh term: Hypothyroidism
  mesh term: Syndrome
  mesh term: Letrozole
  sharing ipd: No
  ipd description: To protect participant confidentiality, individual-level data from this study will not be made publicly available. However, de-identified aggregated data and results can be shared with other researchers upon request after publication. Any data provided will be limited, non-identifiable, and subject to a data use agreement to ensure participant privacy. Only select excerpts needed to validate findings will be shared under approved research objectives. The investigators reserve the right to reject requests that may compromise anonymity. We aim to promote transparency through controlled data access rather than public availability of the full dataset due to re-identification risks for participants.