<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/NCT01672801</url>
  </required_header>
  <id_info>
    <org_study_id>2012P-000186</org_study_id>
    <nct_id>NCT01672801</nct_id>
  </id_info>
  <brief_title>Nimodipine to Prevent LH Surge During Ovulation Induction: Blinded Placebo-controlled RCT</brief_title>
  <acronym>NIMO</acronym>
  <official_title>Using Nimodipine, a Calcium Channel Blocker, to Prevent LH Surge in Women Undergoing Controlled Ovarian Stimulation and Intrauterine Insemination: a Double-blinded, Randomized Controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boston IVF</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Village Fertility Pharmacy</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Boston IVF</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main purpose of this study is to test the effectiveness of nimodipine in preventing a&#xD;
      luteinizing hormone (LH) surge in women undergoing ovulation induction with clomiphene&#xD;
      citrate. It is important to prevent the premature LH surge in controlled ovarian stimulation&#xD;
      to allow adequate recruitment of follicles, proper maturation of a dominant follicle before&#xD;
      ovulation, and effectively time insemination with semen to allow fertilization of a mature&#xD;
      egg to occur.&#xD;
&#xD;
      The investigators are also conducting this study to determine medication side effect profile&#xD;
      (including lightheadedness or dizziness from low blood pressure or rapid heart rate,&#xD;
      headache, and nausea), patient treatment compliance, and clinical pregnancy (positive&#xD;
      pregnancy test and ultrasound evidence of fetal heart rate). Finally, LH and follicle&#xD;
      stimulating hormone (FSH) serum levels will be measured to determine effect of nimodipine on&#xD;
      these hormones.&#xD;
&#xD;
      As a calcium channel blocker, nimodipine has been shown to block calcium mediated release of&#xD;
      gonadotropin releasing hormone in animal and preliminary human studies. The investigators&#xD;
      hypothesize that nimodipine, a calcium channel blocker, will prevent or delay the LH surge&#xD;
      during controlled ovarian stimulation cycles using clomiphene citrate in subfertile patients&#xD;
      undergoing assisted reproduction with intrauterine insemination (IUI).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After enrollment, subjects will be randomized to Placebo Comparator or Active Comparator. All&#xD;
      subjects will receive Clomid 100 mg for 5 days for the purpose of ovarian follicle&#xD;
      recruitment. Intervention will be initiated once ovarian follicle maturation has been&#xD;
      documented (≥1 ovarian follicle size of ≥ 17mm) and the absence of a premature LH surge has&#xD;
      been confirmed - this will be classified as intervention day 0. Subjects will receive their&#xD;
      assigned comparator (Placebo or Active) according the schedule below:&#xD;
&#xD;
        -  Intervention Day 0 - noon / afternoon / bedtime (3 doses)&#xD;
&#xD;
        -  Intervention Day 1 - morning / noon / afternoon / bedtime (4 doses)&#xD;
&#xD;
        -  Intervention Day 2 - morning (1 dose) Serum hormone levels and ultrasound examination&#xD;
           will occur on days 0,1 and 2 for all subjects.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2012</start_date>
  <completion_date type="Actual">April 2014</completion_date>
  <primary_completion_date type="Actual">April 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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>LH Surge</measure>
    <time_frame>7 days</time_frame>
    <description>Compare the change between placebo treated and nimodipine treated patients by the presence or absence of an LH surge on intervention Day 1 and Day 2. LH surge will be determined by serum LH levels at least two times the baseline serum LH (baseline serum LH = (cycle day 3 serum [LH] + cycle day 7 serum [LH])/2).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Experiencing Side Effects</measure>
    <time_frame>Starting day 0 of intervention to pregnancy test (approximately 15 days)</time_frame>
    <description>Medication side effect profile including: symptomatic hypotension (Note: vital signs will be recorded), symptomatic tachycardia (Note: vital signs will be recorded), headache, nausea. These will be self-reported with constructed questionnaire.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Gonadotropin Levels</measure>
    <time_frame>Intervention day 0 to ovulation (approximately 1-7 days)</time_frame>
    <description>Calculated changes in serum LH, FSH, and estradiol levels between patients in nimodipine and placebo arms</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Unexplained Infertility</condition>
  <condition>Polycystic Ovarian Syndrome</condition>
  <condition>Anovulatory</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>All subjects in both arms will receive Clomid 100 mg tablets by mouth for 5 days prior to receiving either placebo comparator or active comparator. Placebo comparator subjects will receive 8 total doses of liquid placebo orally 4 times a day for 8 total doses in pre-filled liquid placebo containing syringes</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Nimodipine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>All subjects in both arms will receive Clomid 100 mg tablets by mouth for 5 days prior to receiving either placebo comparator or active comparator. Active comparator subjects will receive Nimodipine 30mg liquid orally 4 times a day for 8 total doses in pre-filled syringes</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>oral administration</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nimodipine</intervention_name>
    <description>oral administration</description>
    <arm_group_label>Nimodipine</arm_group_label>
    <other_name>Nimotop</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 25-40 years at the time of enrollment&#xD;
&#xD;
          -  Both ovaries intact by history and ultrasound assessment&#xD;
&#xD;
          -  Early follicular phase (day 2-4) serum FSH level &lt;20 mIU/mL&#xD;
&#xD;
          -  Diagnosis of subfertility with a recommended treatment of COH and IUI&#xD;
&#xD;
          -  Providing written informed consent in English&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Body mass index (BMI) &gt;38 kg/m2&#xD;
&#xD;
          -  Early follicular phase (day 2-4) serum FSH level ≥20 mIU/mL&#xD;
&#xD;
          -  History of overstimulated cycle defined as &gt;3 mature follicles of ≥17 mm&#xD;
&#xD;
          -  Abnormal uterine cavity and/or tubal disease (as evidenced by sonohysterogram or&#xD;
             hysterosalpingogram)&#xD;
&#xD;
          -  Diagnosis of infertility with a clear indication for in-vitro fertilization, such as&#xD;
             bilateral tubal occlusion&#xD;
&#xD;
          -  Severe male factor infertility: Total Motile Sperm Count &lt; 2x106 post washing (sperm&#xD;
             deemed inadequate for IUI preparation)&#xD;
&#xD;
          -  Any ovarian or abdominal abnormality that may interfere with adequate TV ultrasound&#xD;
             evaluation&#xD;
&#xD;
          -  Absence of one or both ovaries&#xD;
&#xD;
          -  Any contraindication to being pregnant or carrying a pregnancy to term&#xD;
&#xD;
          -  Unexplained gynecological bleeding&#xD;
&#xD;
          -  Any medical condition that would jeopardize the patient or the integrity of the data&#xD;
             obtained including:&#xD;
&#xD;
          -  Prior reaction or side effects from previous calcium channel blocker use&#xD;
&#xD;
          -  Any medical condition that may interfere with the absorption, distribution, metabolism&#xD;
             or excretion of nimodipine such as hepatic disease, hypertension, seizure, concurrent&#xD;
             infection, depression, reflux (see #12 below).&#xD;
&#xD;
          -  Mental health status resulting in cognitive or emotional impairment that would&#xD;
             preclude study participation&#xD;
&#xD;
          -  The concurrent use of any of the following drugs: [These medications have been shown&#xD;
             to effect the availability of the medication or worsen hypotension symptoms]&#xD;
&#xD;
          -  Antihypertensives (eg. ACE inhibitors, alpha-adrenergic blocking agents,methyldopa,&#xD;
             beta-blockers, diuretics, PDE5 inhibitors, and other calcium antagonists)&#xD;
&#xD;
          -  Antiepileptics (eg. phenobarbital, phenytoin, carbamazepine or valproic acid)&#xD;
&#xD;
          -  Macrolide antibiotics (eg, erythromycin)&#xD;
&#xD;
          -  Azole antimycotics (eg, ketoconazole)&#xD;
&#xD;
          -  HIV protease inhibitors (eg, ritonavir)&#xD;
&#xD;
          -  Antidepressants (eg, nefazodone and fluoxetine)&#xD;
&#xD;
          -  Cimetidine&#xD;
&#xD;
          -  Patient unable to communicate adequately with the investigators and to comply with the&#xD;
             requirements of the study&#xD;
&#xD;
          -  Unwillingness to give written informed consent&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alan S Penzias, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Beth Israel Deaconess Medical Center / Boston IVF</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Boston IVF</name>
      <address>
        <city>Waltham</city>
        <state>Massachusetts</state>
        <zip>02451</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Chen EC, Javors MA, Norris C, Siler-Khodr T, Schenken RS, King TS. Dependence of 3',5'-cyclic adenosine monophosphate--stimulated gonadotropin-releasing hormone release on intracellular calcium levels and L-type calcium channels in superfused GT1-7 neurons. J Soc Gynecol Investig. 2004 Sep;11(6):393-8. doi: 10.1016/j.jsgi.2004.02.010.</citation>
    <PMID>15350253</PMID>
  </reference>
  <reference>
    <citation>Krsmanovic LZ, Stojilkovic SS, Merelli F, Dufour SM, Virmani MA, Catt KJ. Calcium signaling and episodic secretion of gonadotropin-releasing hormone in hypothalamic neurons. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8462-6. doi: 10.1073/pnas.89.18.8462.</citation>
    <PMID>1326758</PMID>
  </reference>
  <reference>
    <citation>Nunez L, Villalobos C, Boockfor FR, Frawley LS. The relationship between pulsatile secretion and calcium dynamics in single, living gonadotropin-releasing hormone neurons. Endocrinology. 2000 Jun;141(6):2012-7. doi: 10.1210/endo.141.6.7491.</citation>
    <PMID>10830284</PMID>
  </reference>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>August 22, 2012</study_first_submitted>
  <study_first_submitted_qc>August 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 27, 2012</study_first_posted>
  <results_first_submitted>July 13, 2020</results_first_submitted>
  <results_first_submitted_qc>August 10, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">August 11, 2020</results_first_posted>
  <last_update_submitted>August 10, 2020</last_update_submitted>
  <last_update_submitted_qc>August 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 11, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Boston IVF</investigator_affiliation>
    <investigator_full_name>Alan Penzias</investigator_full_name>
    <investigator_title>Associate Professor of Obstetrics, Gynecology and Reproductive Biology</investigator_title>
  </responsible_party>
  <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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nimodipine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>All subjects in both arms will receive Clomid 100 mg tablets by mouth for 5 days prior to receiving either placebo comparator or active comparator. Placebo comparator subjects will receive 8 total doses of liquid placebo orally 4 times a day for 8 total doses in pre-filled liquid placebo containing syringes&#xD;
Placebo: oral administration</description>
        </group>
        <group group_id="P2">
          <title>Nimodipine</title>
          <description>All subjects in both arms will receive Clomid 100 mg tablets by mouth for 5 days prior to receiving either placebo comparator or active comparator. Active comparator subjects will receive Nimodipine 30mg liquid orally 4 times a day for 8 total doses in pre-filled syringes&#xD;
Nimodipine: oral administration</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Screen Failure</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>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>All subjects in both arms will receive Clomid 100 mg tablets by mouth for 5 days prior to receiving either placebo comparator or active comparator. Placebo comparator subjects will receive 8 total doses of liquid placebo orally 4 times a day for 8 total doses in pre-filled liquid placebo containing syringes&#xD;
Placebo: oral administration</description>
        </group>
        <group group_id="B2">
          <title>Nimodipine</title>
          <description>All subjects in both arms will receive Clomid 100 mg tablets by mouth for 5 days prior to receiving either placebo comparator or active comparator. Active comparator subjects will receive Nimodipine 30mg liquid orally 4 times a day for 8 total doses in pre-filled syringes&#xD;
Nimodipine: oral administration</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="9"/>
            <count group_id="B2" value="9"/>
            <count group_id="B3" value="18"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33" lower_limit="31" upper_limit="36"/>
                    <measurement group_id="B2" value="37" lower_limit="31" upper_limit="42"/>
                    <measurement group_id="B3" value="35" lower_limit="31" upper_limit="42"/>
                  </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="9"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="18"/>
                  </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>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="8"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="17"/>
                  </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_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>LH Surge</title>
        <description>Compare the change between placebo treated and nimodipine treated patients by the presence or absence of an LH surge on intervention Day 1 and Day 2. LH surge will be determined by serum LH levels at least two times the baseline serum LH (baseline serum LH = (cycle day 3 serum [LH] + cycle day 7 serum [LH])/2).</description>
        <time_frame>7 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>All subjects in both arms will receive Clomid 100 mg tablets by mouth for 5 days prior to receiving either placebo comparator or active comparator. Placebo comparator subjects will receive 8 total doses of liquid placebo orally 4 times a day for 8 total doses in pre-filled liquid placebo containing syringes&#xD;
Placebo: oral administration</description>
          </group>
          <group group_id="O2">
            <title>Nimodipine</title>
            <description>All subjects in both arms will receive Clomid 100 mg tablets by mouth for 5 days prior to receiving either placebo comparator or active comparator. Active comparator subjects will receive Nimodipine 30mg liquid orally 4 times a day for 8 total doses in pre-filled syringes&#xD;
Nimodipine: oral administration</description>
          </group>
        </group_list>
        <measure>
          <title>LH Surge</title>
          <description>Compare the change between placebo treated and nimodipine treated patients by the presence or absence of an LH surge on intervention Day 1 and Day 2. LH surge will be determined by serum LH levels at least two times the baseline serum LH (baseline serum LH = (cycle day 3 serum [LH] + cycle day 7 serum [LH])/2).</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Experiencing Side Effects</title>
        <description>Medication side effect profile including: symptomatic hypotension (Note: vital signs will be recorded), symptomatic tachycardia (Note: vital signs will be recorded), headache, nausea. These will be self-reported with constructed questionnaire.</description>
        <time_frame>Starting day 0 of intervention to pregnancy test (approximately 15 days)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>All subjects in both arms will receive Clomid 100 mg tablets by mouth for 5 days prior to receiving either placebo comparator or active comparator. Placebo comparator subjects will receive 8 total doses of liquid placebo orally 4 times a day for 8 total doses in pre-filled liquid placebo containing syringes&#xD;
Placebo: oral administration</description>
          </group>
          <group group_id="O2">
            <title>Nimodipine</title>
            <description>All subjects in both arms will receive Clomid 100 mg tablets by mouth for 5 days prior to receiving either placebo comparator or active comparator. Active comparator subjects will receive Nimodipine 30mg liquid orally 4 times a day for 8 total doses in pre-filled syringes&#xD;
Nimodipine: oral administration</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Experiencing Side Effects</title>
          <description>Medication side effect profile including: symptomatic hypotension (Note: vital signs will be recorded), symptomatic tachycardia (Note: vital signs will be recorded), headache, nausea. These will be self-reported with constructed questionnaire.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Gonadotropin Levels</title>
        <description>Calculated changes in serum LH, FSH, and estradiol levels between patients in nimodipine and placebo arms</description>
        <time_frame>Intervention day 0 to ovulation (approximately 1-7 days)</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>All subjects in both arms will receive Clomid 100 mg tablets by mouth for 5 days prior to receiving either placebo comparator or active comparator. Placebo comparator subjects will receive 8 total doses of liquid placebo orally 4 times a day for 8 total doses in pre-filled liquid placebo containing syringes&#xD;
Placebo: oral administration</description>
        </group>
        <group group_id="E2">
          <title>Nimodipine</title>
          <description>All subjects in both arms will receive Clomid 100 mg tablets by mouth for 5 days prior to receiving either placebo comparator or active comparator. Active comparator subjects will receive Nimodipine 30mg liquid orally 4 times a day for 8 total doses in pre-filled syringes&#xD;
Nimodipine: oral administration</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="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>1</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="4" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </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>Alan Penzias</name_or_title>
      <organization>Boston IVF</organization>
      <phone>781-434-6500</phone>
      <email>apenzias@bostonivf.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/NCT01672801
org study id: 2012P-000186
nct id: NCT01672801
lead sponsor: 
collaborator: 
has dmc: Yes
The main purpose of this study is to test the effectiveness of nimodipine in preventing a
      luteinizing hormone (LH) surge in women undergoing ovulation induction with clomiphene
      citrate. It is important to prevent the premature LH surge in controlled ovarian stimulation
      to allow adequate recruitment of follicles, proper maturation of a dominant follicle before
      ovulation, and effectively time insemination with semen to allow fertilization of a mature
      egg to occur.

      The investigators are also conducting this study to determine medication side effect profile
      (including lightheadedness or dizziness from low blood pressure or rapid heart rate,
      headache, and nausea), patient treatment compliance, and clinical pregnancy (positive
      pregnancy test and ultrasound evidence of fetal heart rate). Finally, LH and follicle
      stimulating hormone (FSH) serum levels will be measured to determine effect of nimodipine on
      these hormones.

      As a calcium channel blocker, nimodipine has been shown to block calcium mediated release of
      gonadotropin releasing hormone in animal and preliminary human studies. The investigators
      hypothesize that nimodipine, a calcium channel blocker, will prevent or delay the LH surge
      during controlled ovarian stimulation cycles using clomiphene citrate in subfertile patients
      undergoing assisted reproduction with intrauterine insemination (IUI).
After enrollment, subjects will be randomized to Placebo Comparator or Active Comparator. All
      subjects will receive Clomid 100 mg for 5 days for the purpose of ovarian follicle
      recruitment. Intervention will be initiated once ovarian follicle maturation has been
      documented (≥1 ovarian follicle size of ≥ 17mm) and the absence of a premature LH surge has
      been confirmed - this will be classified as intervention day 0. Subjects will receive their
      assigned comparator (Placebo or Active) according the schedule below:

        -  Intervention Day 0 - noon / afternoon / bedtime (3 doses)

        -  Intervention Day 1 - morning / noon / afternoon / bedtime (4 doses)

        -  Intervention Day 2 - morning (1 dose) Serum hormone levels and ultrasound examination
           will occur on days 0,1 and 2 for all subjects.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: LH Surge
time frame: 7 days
description: Compare the change between placebo treated and nimodipine treated patients by the presence or absence of an LH surge on intervention Day 1 and Day 2. LH surge will be determined by serum LH levels at least two times the baseline serum LH (baseline serum LH = (cycle day 3 serum [LH] + cycle day 7 serum [LH])/2).
measure: Number of Participants Experiencing Side Effects
time frame: Starting day 0 of intervention to pregnancy test (approximately 15 days)
description: Medication side effect profile including: symptomatic hypotension (Note: vital signs will be recorded), symptomatic tachycardia (Note: vital signs will be recorded), headache, nausea. These will be self-reported with constructed questionnaire.
measure: Gonadotropin Levels
time frame: Intervention day 0 to ovulation (approximately 1-7 days)
description: Calculated changes in serum LH, FSH, and estradiol levels between patients in nimodipine and placebo arms
arm group label: Placebo
arm group type: Placebo Comparator
description: All subjects in both arms will receive Clomid 100 mg tablets by mouth for 5 days prior to receiving either placebo comparator or active comparator. Placebo comparator subjects will receive 8 total doses of liquid placebo orally 4 times a day for 8 total doses in pre-filled liquid placebo containing syringes
arm group label: Nimodipine
arm group type: Active Comparator
description: All subjects in both arms will receive Clomid 100 mg tablets by mouth for 5 days prior to receiving either placebo comparator or active comparator. Active comparator subjects will receive Nimodipine 30mg liquid orally 4 times a day for 8 total doses in pre-filled syringes
intervention type: Drug
intervention name: Placebo
description: oral administration
arm group label: Placebo
intervention type: Drug
intervention name: Nimodipine
description: oral administration
arm group label: Nimodipine
other name: Nimotop
criteria: 
gender: Female
minimum age: 25 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Alan S Penzias, MD
role: Principal Investigator
affiliation: Beth Israel Deaconess Medical Center / Boston IVF
facility: 
country: United States
citation: Chen EC, Javors MA, Norris C, Siler-Khodr T, Schenken RS, King TS. Dependence of 3',5'-cyclic adenosine monophosphate--stimulated gonadotropin-releasing hormone release on intracellular calcium levels and L-type calcium channels in superfused GT1-7 neurons. J Soc Gynecol Investig. 2004 Sep;11(6):393-8. doi: 10.1016/j.jsgi.2004.02.010.
PMID: 15350253
citation: Krsmanovic LZ, Stojilkovic SS, Merelli F, Dufour SM, Virmani MA, Catt KJ. Calcium signaling and episodic secretion of gonadotropin-releasing hormone in hypothalamic neurons. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8462-6. doi: 10.1073/pnas.89.18.8462.
PMID: 1326758
citation: Nunez L, Villalobos C, Boockfor FR, Frawley LS. The relationship between pulsatile secretion and calcium dynamics in single, living gonadotropin-releasing hormone neurons. Endocrinology. 2000 Jun;141(6):2012-7. doi: 10.1210/endo.141.6.7491.
PMID: 10830284
responsible party type: Principal Investigator
investigator affiliation: Boston IVF
investigator full name: Alan Penzias
investigator title: Associate Professor of Obstetrics, Gynecology and Reproductive Biology
mesh term: Polycystic Ovary Syndrome
mesh term: Infertility
mesh term: Nimodipine
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 