<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/NCT03774407</url>
  </required_header>
  <id_info>
    <org_study_id>L19-020</org_study_id>
    <nct_id>NCT03774407</nct_id>
  </id_info>
  <brief_title>Vaginal Estriol in Multiple Sclerosis</brief_title>
  <official_title>Dual Benefits of Vaginal Estriol: Improved Urogenital Health and Re-myelination in Relapsing Remitting Multiple Sclerosis (RRMS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Texas Tech University Health Sciences Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Texas Tech University Health Sciences Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Study to evaluate the efficiency of vaginal estriol, as a treatment for urogenital symptoms&#xD;
      in female patients with RRMS. The secondary objective is to evaluate the potential role of&#xD;
      vaginal estriol in re-myelination in RRMS patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Pilot project to determine the effectiveness of 1 mg transvaginal estriol, as an adjunctive&#xD;
      therapy for female MS patients. The goal is to recruit 20 patients from the MS clinic in the&#xD;
      neurology department of Texas Tech University Health Sciences Center. This study has been&#xD;
      planned in collaboration with reproductive endocrinology, endocrinology, gynecology and basic&#xD;
      science. The 1mg transvaginal dose was chosen after careful search of the literature and&#xD;
      consultation with collaborators.&#xD;
&#xD;
      Single-group pilot study.&#xD;
&#xD;
      Subjects:&#xD;
&#xD;
      Patients with relapsing remitting MS and urogenital symptoms (frequency, urgency, frequent&#xD;
      urinary tract infections, incontinence) will be invited to participate in the study.&#xD;
      Enrollment will be during their scheduled clinic appointment. Some candidates (patients of&#xD;
      the primary investigator) may be contacted by phone and invited to participate in the study.&#xD;
&#xD;
      The clinical trial will be explained to potential participants in detail, reviewing the&#xD;
      objectives and methodology of the study. There will be adequate time allotted to answer any&#xD;
      questions or concerns from the potential participants. Those patients interested in&#xD;
      participating in the study will be asked to sign the consent form. In order to remind&#xD;
      patients about their follow-up visits, lab work, etc., they will be contacted routinely.&#xD;
      Participants will be instructed to call in case of questions or concerns.&#xD;
&#xD;
      Patients will be evaluated clinically during their scheduled follow up in which a full&#xD;
      neurological exam will be performed during each visit. Patients will be instructed by the&#xD;
      primary investigator how to correctly use the vaginal cream. This will be done at their&#xD;
      enrolment and reinforced by the principal investigator, during their follow up visits.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 20, 2019</start_date>
  <completion_date type="Actual">November 29, 2020</completion_date>
  <primary_completion_date type="Actual">November 10, 2020</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>This is a single-group prospective repeated-measures pilot trial. Duration is 12 months,</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Bladder Control Scale (BLCS)</measure>
    <time_frame>baseline and 9 months</time_frame>
    <description>The questions are regarding control of the bladder, number of accidents in the past 4 weeks, alteration of activities because of bladder problems and restriction on lifestyle because of bladder problems. The total score for the BLCS is the sum of the scores for the 4 items. Scores can range from 0-22, with higher scores indicating greater bladder control problems. Change from baseline at 9 months.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Visual Evoked Potential and Ocular Tomography Results From Baseline to 9 Months of Both Eyes</measure>
    <time_frame>Baseline and 9 months</time_frame>
    <description>visual evoked potential measured in each eye at baseline and 9 months normal value should be bellow 100 milliseconds</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in MS Quality of Life Questionnaire at Baseline and 9 Months. (Physical Score)</measure>
    <time_frame>Quality of life score at baseline and Quality of life score at 9 months</time_frame>
    <description>Multiple sclerosis quality of life questionnaire is an extensive questionnaire filled by the patient and graded by physician. It consists of 2 main areas the physical health which include physical function, health perceptions, energy fatigue, role limitations, pain, sexual function, social function and health distress. The mental health score which includes health distress, overall quality of life, emotional wellbeing, role limitations and cognitive function. The physical health and mental health parts each include a possible score range of 0-100. Overall the lower the score the better</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Multiple Sclerosis</condition>
  <condition>Neurogenic Bladder</condition>
  <arm_group>
    <arm_group_label>urogenital symptoms</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>To evaluate the efficiency of vaginal estriol, as a treatment for urogenital symptoms in female patients with RRMS.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>remyelination</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>To evaluate the potential role of vaginal estriol in re-myelination in RRMS patients.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>vaginal estriol</intervention_name>
    <description>Estriol vaginal cream will be formulated by Twin Oaks specialty pharmacy-by the same compound specialist. 30 mg estriol powder will be mixed with 5 mL of propylene glycol and 22 g of vaginal base cream. The product can be stored at room temperature and has a shelf life of up to 4 months. It comes with an applicator.</description>
    <arm_group_label>remyelination</arm_group_label>
    <arm_group_label>urogenital symptoms</arm_group_label>
    <other_name>estriol cream</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Female patients with RRMS over the age of 40 to 65.&#xD;
&#xD;
               -  Being prescribed vaginal estriol to treat their urogenital symptoms such as&#xD;
                  frequency, urgency, incontinence and frequent urinary tract infections.&#xD;
&#xD;
               -  Patients that had underwent chemical or surgical hysterectomy.&#xD;
&#xD;
          2. Patients will continue their current disease modifying agent for MS during the trial.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with history of breast cancer, uterine or ovarian cancer.&#xD;
&#xD;
          2. Patients with progressive multiple sclerosis&#xD;
&#xD;
          3. Patients who are unable to undergo an MRI&#xD;
&#xD;
          4. Males&#xD;
&#xD;
          5. Patient is already on vaginal or oral or transdermal estrogens&#xD;
&#xD;
          6. Pregnant or breast-feeding patients&#xD;
&#xD;
          7. Patient taking sex hormones eg testosterone for libido&#xD;
&#xD;
          8. Patients taking DHEA or OTC related products that could influence the hormonal milieu.&#xD;
&#xD;
          9. Patient with prolapse uterus or conditions that would impact on transvaginal&#xD;
             absorption of estriol&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>female</gender_description>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mirla Avila</last_name>
    <role>Principal Investigator</role>
    <affiliation>Texas Tech University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Texas Tech University Health Sciences Center</name>
      <address>
        <city>Lubbock</city>
        <state>Texas</state>
        <zip>79430</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Avila-Ornelas J, Avila M, Stosic M, Robles L, Prieto PG, Hutton GJ, Rivera VM. The role of postpartum intravenous corticosteroids in the prevention of relapses in multiple sclerosis. Int J MS Care. 2011 Summer;13(2):91-3. doi: 10.7224/1537-2073-13.2.91.</citation>
    <PMID>24453710</PMID>
  </results_reference>
  <results_reference>
    <citation>Cody JD, Jacobs ML, Richardson K, Moehrer B, Hextall A. Oestrogen therapy for urinary incontinence in post-menopausal women. Cochrane Database Syst Rev. 2012 Oct 17;10(10):CD001405. doi: 10.1002/14651858.CD001405.pub3.</citation>
    <PMID>23076892</PMID>
  </results_reference>
  <results_reference>
    <citation>Harlow DE, Honce JM, Miravalle AA. Remyelination Therapy in Multiple Sclerosis. Front Neurol. 2015 Dec 10;6:257. doi: 10.3389/fneur.2015.00257. eCollection 2015.</citation>
    <PMID>26696956</PMID>
  </results_reference>
  <results_reference>
    <citation>Mallik S, Samson RS, Wheeler-Kingshott CA, Miller DH. Imaging outcomes for trials of remyelination in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2014 Dec;85(12):1396-404. doi: 10.1136/jnnp-2014-307650. Epub 2014 Apr 25.</citation>
    <PMID>24769473</PMID>
  </results_reference>
  <results_reference>
    <citation>Moore KH. The costs of urinary incontinence. Med J Aust. 2001 May 7;174(9):436-7. doi: 10.5694/j.1326-5377.2001.tb143368.x. No abstract available.</citation>
    <PMID>11386586</PMID>
  </results_reference>
  <results_reference>
    <citation>Rahn DD, Carberry C, Sanses TV, Mamik MM, Ward RM, Meriwether KV, Olivera CK, Abed H, Balk EM, Murphy M; Society of Gynecologic Surgeons Systematic Review Group. Vaginal estrogen for genitourinary syndrome of menopause: a systematic review. Obstet Gynecol. 2014 Dec;124(6):1147-1156. doi: 10.1097/AOG.0000000000000526.</citation>
    <PMID>25415166</PMID>
  </results_reference>
  <results_reference>
    <citation>Tiwari-Woodruff S, Voskuhl RR. Neuroprotective and anti-inflammatory effects of estrogen receptor ligand treatment in mice. J Neurol Sci. 2009 Nov 15;286(1-2):81-5. doi: 10.1016/j.jns.2009.04.023. Epub 2009 May 13.</citation>
    <PMID>19442988</PMID>
  </results_reference>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>December 5, 2018</study_first_submitted>
  <study_first_submitted_qc>December 10, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 13, 2018</study_first_posted>
  <results_first_submitted>January 7, 2022</results_first_submitted>
  <results_first_submitted_qc>August 25, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">September 21, 2022</results_first_posted>
  <last_update_submitted>August 25, 2022</last_update_submitted>
  <last_update_submitted_qc>August 25, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>remyelination</keyword>
  <keyword>urogenital health</keyword>
  <keyword>multiple sclerosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Urinary Bladder, Neurogenic</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 13, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/07/NCT03774407/Prot_SAP_002.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>May 6, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/07/NCT03774407/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>one participant was enrolled twice</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Vaginal Estriol as a Potential Adjunctive Therapy for MS Remyelination</title>
          <description>Pilot study at TTUHSC department of neurology, MS clinic. Adjunctive vaginal estriol (1mg) was offered to patient with RRMS. MRI brain with and without contrast, VEP and OCT obtained at baseline and 9 months. Multiple sclerosis quality of life-54(MSQOL-54) mental and physical were performed at first encounter and 9 months. Vaginal estriol is absorbed more naturally, levels of FSH, estriol and LH were done at baseline and 9 months. Total 12 patients included.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Vaginal Estriol as a Potential Adjunctive Therapy for MS Remyelination</title>
          <description>To evaluate the efficiency of vaginal estriol, as a treatment for urogenital symptoms in female patients with RRMS.&#xD;
vaginal estriol: Estriol vaginal cream will be formulated by Twin Oaks specialty pharmacy-by the same compound specialist. 30 mg estriol powder will be mixed with 5 mL of propylene glycol and 22 g of vaginal base cream. The product can be stored at room temperature and has a shelf life of up to 4 months. It comes with an applicator.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="12"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="52" spread="6.9"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Bladder Control Scale (BLCS)</title>
        <description>The questions are regarding control of the bladder, number of accidents in the past 4 weeks, alteration of activities because of bladder problems and restriction on lifestyle because of bladder problems. The total score for the BLCS is the sum of the scores for the 4 items. Scores can range from 0-22, with higher scores indicating greater bladder control problems. Change from baseline at 9 months.</description>
        <time_frame>baseline and 9 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Urogenital Symptoms</title>
            <description>Evaluate the efficiency of vaginal estriol, as a treatment for urogenital symptoms in female patients with RRMS.&#xD;
vaginal estriol: Estriol vaginal cream will be formulated by Twin Oaks specialty pharmacy-by the same compound specialist. 30 mg estriol powder will be mixed with 5 mL of propylene glycol and 22 g of vaginal base cream. The product can be stored at room temperature and has a shelf life of up to 4 months. It comes with an applicator.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Bladder Control Scale (BLCS)</title>
          <description>The questions are regarding control of the bladder, number of accidents in the past 4 weeks, alteration of activities because of bladder problems and restriction on lifestyle because of bladder problems. The total score for the BLCS is the sum of the scores for the 4 items. Scores can range from 0-22, with higher scores indicating greater bladder control problems. Change from baseline at 9 months.</description>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9" lower_limit="-11" upper_limit="-7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.002</p_value>
            <p_value_desc>This P value reported was for bladder urinary frequency change from baseline to 9 months</p_value_desc>
            <method>p value</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Visual Evoked Potential and Ocular Tomography Results From Baseline to 9 Months of Both Eyes</title>
        <description>visual evoked potential measured in each eye at baseline and 9 months normal value should be bellow 100 milliseconds</description>
        <time_frame>Baseline and 9 months</time_frame>
        <population>patients were evaluated at baseline and 9 months</population>
        <group_list>
          <group group_id="O1">
            <title>Ocular Tomography</title>
            <description>ocular tomography (evaluates the thickness of the retina) measured in each eye at baseline and 9 months</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Visual Evoked Potential and Ocular Tomography Results From Baseline to 9 Months of Both Eyes</title>
          <description>visual evoked potential measured in each eye at baseline and 9 months normal value should be bellow 100 milliseconds</description>
          <population>patients were evaluated at baseline and 9 months</population>
          <units>millisecond</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>R EYE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.4" spread="10.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>L EYE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.7" spread="14.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in MS Quality of Life Questionnaire at Baseline and 9 Months. (Physical Score)</title>
        <description>Multiple sclerosis quality of life questionnaire is an extensive questionnaire filled by the patient and graded by physician. It consists of 2 main areas the physical health which include physical function, health perceptions, energy fatigue, role limitations, pain, sexual function, social function and health distress. The mental health score which includes health distress, overall quality of life, emotional wellbeing, role limitations and cognitive function. The physical health and mental health parts each include a possible score range of 0-100. Overall the lower the score the better</description>
        <time_frame>Quality of life score at baseline and Quality of life score at 9 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Quality of Life Questionnaire</title>
            <description>quality of life questionnaire to be compared at baseline and 9 months</description>
          </group>
        </group_list>
        <measure>
          <title>Change in MS Quality of Life Questionnaire at Baseline and 9 Months. (Physical Score)</title>
          <description>Multiple sclerosis quality of life questionnaire is an extensive questionnaire filled by the patient and graded by physician. It consists of 2 main areas the physical health which include physical function, health perceptions, energy fatigue, role limitations, pain, sexual function, social function and health distress. The mental health score which includes health distress, overall quality of life, emotional wellbeing, role limitations and cognitive function. The physical health and mental health parts each include a possible score range of 0-100. Overall the lower the score the better</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Quality of life Physical score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.87" spread="16.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Quality of life Mental score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.8" spread="17.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>baseline and 9 months</time_frame>
      <desc>Between baseline and 9 months</desc>
      <group_list>
        <group group_id="E1">
          <title>Vaginal Estriol as a Potential Adjunctive Therapy for MS Remyelination</title>
          <description>no adverse events were reported</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="12"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>Dr Mirla Avila</name_or_title>
      <organization>Texas Tech</organization>
      <phone>8322448072</phone>
      <email>mirla.avila@ttuhsc.edu</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/NCT03774407
org study id: L19-020
nct id: NCT03774407
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Study to evaluate the efficiency of vaginal estriol, as a treatment for urogenital symptoms
      in female patients with RRMS. The secondary objective is to evaluate the potential role of
      vaginal estriol in re-myelination in RRMS patients.
Pilot project to determine the effectiveness of 1 mg transvaginal estriol, as an adjunctive
      therapy for female MS patients. The goal is to recruit 20 patients from the MS clinic in the
      neurology department of Texas Tech University Health Sciences Center. This study has been
      planned in collaboration with reproductive endocrinology, endocrinology, gynecology and basic
      science. The 1mg transvaginal dose was chosen after careful search of the literature and
      consultation with collaborators.

      Single-group pilot study.

      Subjects:

      Patients with relapsing remitting MS and urogenital symptoms (frequency, urgency, frequent
      urinary tract infections, incontinence) will be invited to participate in the study.
      Enrollment will be during their scheduled clinic appointment. Some candidates (patients of
      the primary investigator) may be contacted by phone and invited to participate in the study.

      The clinical trial will be explained to potential participants in detail, reviewing the
      objectives and methodology of the study. There will be adequate time allotted to answer any
      questions or concerns from the potential participants. Those patients interested in
      participating in the study will be asked to sign the consent form. In order to remind
      patients about their follow-up visits, lab work, etc., they will be contacted routinely.
      Participants will be instructed to call in case of questions or concerns.

      Patients will be evaluated clinically during their scheduled follow up in which a full
      neurological exam will be performed during each visit. Patients will be instructed by the
      primary investigator how to correctly use the vaginal cream. This will be done at their
      enrolment and reinforced by the principal investigator, during their follow up visits.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: This is a single-group prospective repeated-measures pilot trial. Duration is 12 months,
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Bladder Control Scale (BLCS)
time frame: baseline and 9 months
description: The questions are regarding control of the bladder, number of accidents in the past 4 weeks, alteration of activities because of bladder problems and restriction on lifestyle because of bladder problems. The total score for the BLCS is the sum of the scores for the 4 items. Scores can range from 0-22, with higher scores indicating greater bladder control problems. Change from baseline at 9 months.
measure: Change in Visual Evoked Potential and Ocular Tomography Results From Baseline to 9 Months of Both Eyes
time frame: Baseline and 9 months
description: visual evoked potential measured in each eye at baseline and 9 months normal value should be bellow 100 milliseconds
measure: Change in MS Quality of Life Questionnaire at Baseline and 9 Months. (Physical Score)
time frame: Quality of life score at baseline and Quality of life score at 9 months
description: Multiple sclerosis quality of life questionnaire is an extensive questionnaire filled by the patient and graded by physician. It consists of 2 main areas the physical health which include physical function, health perceptions, energy fatigue, role limitations, pain, sexual function, social function and health distress. The mental health score which includes health distress, overall quality of life, emotional wellbeing, role limitations and cognitive function. The physical health and mental health parts each include a possible score range of 0-100. Overall the lower the score the better
arm group label: urogenital symptoms
arm group type: Other
description: To evaluate the efficiency of vaginal estriol, as a treatment for urogenital symptoms in female patients with RRMS.
arm group label: remyelination
arm group type: Experimental
description: To evaluate the potential role of vaginal estriol in re-myelination in RRMS patients.
intervention type: Drug
intervention name: vaginal estriol
description: Estriol vaginal cream will be formulated by Twin Oaks specialty pharmacy-by the same compound specialist. 30 mg estriol powder will be mixed with 5 mL of propylene glycol and 22 g of vaginal base cream. The product can be stored at room temperature and has a shelf life of up to 4 months. It comes with an applicator.
arm group label: remyelination
arm group label: urogenital symptoms
other name: estriol cream
criteria: 
gender: Female
gender based: Yes
gender description: female
minimum age: 40 Years
maximum age: 65 Years
healthy volunteers: No
last name: Mirla Avila
role: Principal Investigator
affiliation: Texas Tech University
facility: 
country: United States
citation: Avila-Ornelas J, Avila M, Stosic M, Robles L, Prieto PG, Hutton GJ, Rivera VM. The role of postpartum intravenous corticosteroids in the prevention of relapses in multiple sclerosis. Int J MS Care. 2011 Summer;13(2):91-3. doi: 10.7224/1537-2073-13.2.91.
PMID: 24453710
citation: Cody JD, Jacobs ML, Richardson K, Moehrer B, Hextall A. Oestrogen therapy for urinary incontinence in post-menopausal women. Cochrane Database Syst Rev. 2012 Oct 17;10(10):CD001405. doi: 10.1002/14651858.CD001405.pub3.
PMID: 23076892
citation: Harlow DE, Honce JM, Miravalle AA. Remyelination Therapy in Multiple Sclerosis. Front Neurol. 2015 Dec 10;6:257. doi: 10.3389/fneur.2015.00257. eCollection 2015.
PMID: 26696956
citation: Mallik S, Samson RS, Wheeler-Kingshott CA, Miller DH. Imaging outcomes for trials of remyelination in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2014 Dec;85(12):1396-404. doi: 10.1136/jnnp-2014-307650. Epub 2014 Apr 25.
PMID: 24769473
citation: Moore KH. The costs of urinary incontinence. Med J Aust. 2001 May 7;174(9):436-7. doi: 10.5694/j.1326-5377.2001.tb143368.x. No abstract available.
PMID: 11386586
citation: Rahn DD, Carberry C, Sanses TV, Mamik MM, Ward RM, Meriwether KV, Olivera CK, Abed H, Balk EM, Murphy M; Society of Gynecologic Surgeons Systematic Review Group. Vaginal estrogen for genitourinary syndrome of menopause: a systematic review. Obstet Gynecol. 2014 Dec;124(6):1147-1156. doi: 10.1097/AOG.0000000000000526.
PMID: 25415166
citation: Tiwari-Woodruff S, Voskuhl RR. Neuroprotective and anti-inflammatory effects of estrogen receptor ligand treatment in mice. J Neurol Sci. 2009 Nov 15;286(1-2):81-5. doi: 10.1016/j.jns.2009.04.023. Epub 2009 May 13.
PMID: 19442988
responsible party type: Sponsor
mesh term: Multiple Sclerosis
mesh term: Urinary Bladder, Neurogenic
mesh term: Sclerosis
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 