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/NCT05974449</url>
    </required_header>
    <id_info>
      <org_study_id>BC-OFSAE-Lactobacillus</org_study_id>
      <nct_id>NCT05974449</nct_id>
    </id_info>
    <brief_title>Lactobacillus Vaginalis Capsules for Treatment of Vulvovaginal Atrophy in Young Breast Cancer Patients</brief_title>
    <official_title>A Phase II Clinical Study of Lactobacillus Vaginalis Capsules for the Prevention and Treatment of Symptoms of Vulvovaginal Atrophy in Young Breast Cancer Patients Receving Ovarian Function Suppression (OFS) During Chemotherapy</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>The First Affiliated Hospital with Nanjing Medical University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>The First Affiliated Hospital with Nanjing Medical University</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This study is a prospective, randomized controlled, phase II clinical study with a planned&#xD;
        enrolment of 60 patients. The study focuses on the efficacy and safety of Lactobacillus&#xD;
        vaginalis capsules for the prevention and/or treatment of vulvovaginal symptoms in young&#xD;
        breast cancer patients receiving ovarian protection during chemotherapy, in order to improve&#xD;
        compliance and quality of life in breast cancer patients.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Breast cancer is the most common malignancy in women, and its incidence is increasing year by&#xD;
        year. While systemic combination therapy (e.g., Chemotherapy, endocrine therapy, targeted&#xD;
        therapy, etc.) can increase the cure rate of patients, it can also bring about some adverse&#xD;
        effects that can negatively affect the life of patients. The most common form of&#xD;
        chemotherapy, for example, is chemotherapy drugs (especially cyclophosphamide-containing&#xD;
        chemotherapy regimens), which can lead to impaired ovarian function. Inhibition of ovarian&#xD;
        function with gonadotropin-releasing hormone agonists (GnRHa) can achieve protection of the&#xD;
        ovaries during chemotherapy and help restore ovarian function. As the trend towards younger&#xD;
        breast cancer has become more pronounced in recent years, ovarian protection has also&#xD;
        received increasing attention. However, ovarian protection can also dramatically reduce serum&#xD;
        estrogen levels in patients, leading to vulvovaginal symptoms such as vaginal dryness,&#xD;
        difficulty with intercourse, genital skin irritation, itching, burning, and increased vaginal&#xD;
        discharge. Moreover, patients are often too shy to express these symptoms, leading to&#xD;
        underdiagnosis and under-treatment.&#xD;
  &#xD;
        The North American Menopause Society states that topical estrogen therapy is the first-line&#xD;
        option for moderate to severe vulvovaginal symptoms, but its safety in women with breast&#xD;
        cancer is not known. Some studies have shown an increase in serum estradiol levels with the&#xD;
        use of estradiol vaginal rings and creams, and there are no clinical studies to suggest a&#xD;
        relationship between a mild increase and the risk of breast cancer recurrence. and short-term&#xD;
        effects are limited. --The hierarchy is not out: hormonal therapy first, then non-hormonal&#xD;
        therapy The onset of vulvovaginal symptoms is primarily due to a decrease in serum&#xD;
        circulating estrogen in women, but many researchers are beginning to explore whether these&#xD;
        changes can be attributed to changes in the dynamics of the vaginal microbiome. The vaginal&#xD;
        microecology of healthy women is dominated by lactic acid bacteria, which proliferate in the&#xD;
        anaerobic environment of the vagina, producing various antimicrobial compounds such as lactic&#xD;
        acid, hydrogen peroxide (H2O2) and bacteriocins and maintaining vaginal health by enhancing&#xD;
        epithelial barrier function, symbiotic colonization, blocking pathogenic bacterial adhesion,&#xD;
        lowering pH, influencing antimicrobial peptide production/secretion and overall mucosal&#xD;
        immunity. In patients presenting with vulvovaginal symptoms, vaginal microecology is no&#xD;
        longer dominated by lactobacilli and it has been shown that the severity of vaginal dryness,&#xD;
        dyspareunia, and vaginal pain symptoms are negatively correlated with the number of&#xD;
        lactobacilli in the vagina. To address this issue, researchers have explored the fact that&#xD;
        Donders et al. found that Lactobacillus combined with low-dose estrogen significantly&#xD;
        improved vulvovaginal symptoms in women but caused a concomitant increase in serum estradiol,&#xD;
        the risk of which is not yet known in breast cancer patients , whereas this study explored&#xD;
        the use of Lactobacillus alone as an intervention to see if there was an increase in serum&#xD;
        estradiol after the intervention, and prophylactic medication was administered to address&#xD;
        patients who endure vulvovaginal symptoms due to shyness of expression. However, there is a&#xD;
        lack of large randomized controlled clinical studies to determine the effectiveness of&#xD;
        Lactobacillus in modulating or restoring a dysregulated vaginal microbiome and improving&#xD;
        vaginal symptoms in different populations. The aim of this study was to explore, in the small&#xD;
        sample size, whether prophylactic use of Lactobacillus vaginalis capsules during ovarian&#xD;
        protection in breast cancer patients could prevent vulvovaginal symptoms in patients and to&#xD;
        assess its safety in order to improve treatment adherence in breast cancer patients and&#xD;
        improve the quality of life of breast cancer patients.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 24, 2023</start_date>
    <completion_date type="Anticipated">December 30, 2024</completion_date>
    <primary_completion_date type="Anticipated">July 31, 2024</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Crossover Assignment</intervention_model>
      <primary_purpose>Prevention</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Vaginal PH</measure>
      <time_frame>1 year</time_frame>
      <description>Reactive vaginal pH</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES)</measure>
      <time_frame>1year</time_frame>
      <description>For assessing quality of life and vulvovaginal symptoms in women. Using &quot;Absolutely not&quot;, &quot;A little&quot;, &quot;Some&quot;, &quot;Very&quot;, &quot;Extremely&quot; to indicate the severity of symptoms</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>The detection rate of vaginal secretions of Gardnerella vaginalis, Lactobacillus janus, Lactobacillus garciae, Lactobacillus curvatus, Lactobacillus inertus, Lactobacillus chimaerae, Prevotella spp. and Streptococcus spp;</measure>
      <time_frame>1year</time_frame>
      <description>Detection of target flora in vaginal secretions using qPCR. Reflecting changes in vaginal microecology.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Serum concentrations of estrone, estradiol and oestrogen binding protein</measure>
      <time_frame>1 year</time_frame>
      <description>Testing serum hormone levels</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">60</enrollment>
    <condition>Breast Cancer Female</condition>
    <arm_group>
      <arm_group_label>C1, C2 dosing group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>C1 and C2 dosing groups: The drug is administered on the day of the C1 and C2 chemotherapy cycles for 10 days, washing the vulva and placing the drug deep into the vagina, once a night, 1 capsules each time.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>C3, C4 dosing group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>C3 and C4 dosing groups: The drug is given on the day of the C3 and C4 chemotherapy cycles and is administered for 10 days. The drug is placed deep into the vagina after washing the vulva, once a night, 1 capsules each time.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Vaginal Lactobacillus capsules</intervention_name>
      <description>This product is a micro-ecological preparation made from live Lactobacillus and is used for the treatment of vaginosis caused by disorders of the flora.</description>
      <arm_group_label>C1, C2 dosing group</arm_group_label>
      <arm_group_label>C3, C4 dosing group</arm_group_label>
      <other_name>Ding Jun Sheng</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Pathologically confirmed invasive breast cancer (regardless of pathology type);&#xD;
  &#xD;
            2. Female patients 18-40 years of age with unlimited HR, or 41-45 years of age with&#xD;
               negative HR;&#xD;
  &#xD;
            3. Patients expected to receive ≥4 cycles of chemotherapy containing paclitaxel or&#xD;
               anthracycline-containing chemotherapeutic agents and ovarian protective drugs;&#xD;
  &#xD;
            4. Pre-menopausal (including perimenopausal);&#xD;
  &#xD;
            5. Good compliance, normal comprehension and ability to receive treatment as required;&#xD;
  &#xD;
            6. ECOG score 0-1;&#xD;
  &#xD;
            7. Patients volunteered to participate in this study and signed an informed consent form.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Use of any other vaginal medication in the 3 months prior to the study;&#xD;
  &#xD;
            2. Use of any anti-infective medication in the 3 months prior to the study;&#xD;
  &#xD;
            3. Active genital tract infection;&#xD;
  &#xD;
            4. Previous development of other malignancies;&#xD;
  &#xD;
            5. Any reason why they are unable to complete the full course of follow-up treatment as&#xD;
               prescribed by their doctors;&#xD;
  &#xD;
            6. AST and ALT ≥ 1.5 times the upper limit of normal, alkaline phosphatase ≥ 2.5 times&#xD;
               the upper limit of normal, total bilirubin ≥ 1.5 times the upper limit of normal,&#xD;
               serum creatinine ≥ 1.5 times the upper limit of normal; LVEF &lt; 50% on cardiac&#xD;
               ultrasound;&#xD;
  &#xD;
            7. Severe coagulation disorder, severe systemic disease, or uncontrollable infection;&#xD;
  &#xD;
            8. Persons without personal freedom and independent civil capacity; the presence of&#xD;
               mental disorders, addictions, etc., which in the judgment of the investigator do not&#xD;
               qualify for enrolment.&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>45 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Jue Wang, MD</last_name>
      <role>Study Director</role>
      <affiliation>The First Affiliated Hospital with Nanjing Medical University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Ran Zheng</last_name>
      <phone>008615705227155</phone>
      <email>15705227155@163.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Jue Wang, MD</last_name>
      <phone>008618061695508</phone>
      <email>wangjue200011@njmu.edu.cn</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>the First Affiliated Hospital of Nanjing Medical University</name>
        <address>
          <city>Nanjing</city>
          <state>Jiangsu</state>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Jue Wang, MD</last_name>
        <phone>+8618061695508</phone>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 26, 2023</study_first_submitted>
    <study_first_submitted_qc>August 2, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 3, 2023</study_first_posted>
    <last_update_submitted>August 24, 2023</last_update_submitted>
    <last_update_submitted_qc>August 24, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 25, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>The First Affiliated Hospital with Nanjing Medical University</investigator_affiliation>
      <investigator_full_name>Jue Wang</investigator_full_name>
      <investigator_title>Prof.</investigator_title>
    </responsible_party>
    <keyword>Breast cancer, Vulvovaginal symptoms ，Lactobacillus capsules</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Breast Neoplasms</mesh_term>
      <mesh_term>Atrophy</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </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/NCT05974449
  org study id: BC-OFSAE-Lactobacillus
  nct id: NCT05974449
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  This study is a prospective, randomized controlled, phase II clinical study with a planned
        enrolment of 60 patients. The study focuses on the efficacy and safety of Lactobacillus
        vaginalis capsules for the prevention and/or treatment of vulvovaginal symptoms in young
        breast cancer patients receiving ovarian protection during chemotherapy, in order to improve
        compliance and quality of life in breast cancer patients.
  Breast cancer is the most common malignancy in women, and its incidence is increasing year by
        year. While systemic combination therapy (e.g., Chemotherapy, endocrine therapy, targeted
        therapy, etc.) can increase the cure rate of patients, it can also bring about some adverse
        effects that can negatively affect the life of patients. The most common form of
        chemotherapy, for example, is chemotherapy drugs (especially cyclophosphamide-containing
        chemotherapy regimens), which can lead to impaired ovarian function. Inhibition of ovarian
        function with gonadotropin-releasing hormone agonists (GnRHa) can achieve protection of the
        ovaries during chemotherapy and help restore ovarian function. As the trend towards younger
        breast cancer has become more pronounced in recent years, ovarian protection has also
        received increasing attention. However, ovarian protection can also dramatically reduce serum
        estrogen levels in patients, leading to vulvovaginal symptoms such as vaginal dryness,
        difficulty with intercourse, genital skin irritation, itching, burning, and increased vaginal
        discharge. Moreover, patients are often too shy to express these symptoms, leading to
        underdiagnosis and under-treatment.
  
        The North American Menopause Society states that topical estrogen therapy is the first-line
        option for moderate to severe vulvovaginal symptoms, but its safety in women with breast
        cancer is not known. Some studies have shown an increase in serum estradiol levels with the
        use of estradiol vaginal rings and creams, and there are no clinical studies to suggest a
        relationship between a mild increase and the risk of breast cancer recurrence. and short-term
        effects are limited. --The hierarchy is not out: hormonal therapy first, then non-hormonal
        therapy The onset of vulvovaginal symptoms is primarily due to a decrease in serum
        circulating estrogen in women, but many researchers are beginning to explore whether these
        changes can be attributed to changes in the dynamics of the vaginal microbiome. The vaginal
        microecology of healthy women is dominated by lactic acid bacteria, which proliferate in the
        anaerobic environment of the vagina, producing various antimicrobial compounds such as lactic
        acid, hydrogen peroxide (H2O2) and bacteriocins and maintaining vaginal health by enhancing
        epithelial barrier function, symbiotic colonization, blocking pathogenic bacterial adhesion,
        lowering pH, influencing antimicrobial peptide production/secretion and overall mucosal
        immunity. In patients presenting with vulvovaginal symptoms, vaginal microecology is no
        longer dominated by lactobacilli and it has been shown that the severity of vaginal dryness,
        dyspareunia, and vaginal pain symptoms are negatively correlated with the number of
        lactobacilli in the vagina. To address this issue, researchers have explored the fact that
        Donders et al. found that Lactobacillus combined with low-dose estrogen significantly
        improved vulvovaginal symptoms in women but caused a concomitant increase in serum estradiol,
        the risk of which is not yet known in breast cancer patients , whereas this study explored
        the use of Lactobacillus alone as an intervention to see if there was an increase in serum
        estradiol after the intervention, and prophylactic medication was administered to address
        patients who endure vulvovaginal symptoms due to shyness of expression. However, there is a
        lack of large randomized controlled clinical studies to determine the effectiveness of
        Lactobacillus in modulating or restoring a dysregulated vaginal microbiome and improving
        vaginal symptoms in different populations. The aim of this study was to explore, in the small
        sample size, whether prophylactic use of Lactobacillus vaginalis capsules during ovarian
        protection in breast cancer patients could prevent vulvovaginal symptoms in patients and to
        assess its safety in order to improve treatment adherence in breast cancer patients and
        improve the quality of life of breast cancer patients.
  allocation: Randomized
  intervention model: Crossover Assignment
  primary purpose: Prevention
  masking: None (Open Label)
  measure: Vaginal PH
  time frame: 1 year
  description: Reactive vaginal pH
  measure: Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES)
  time frame: 1year
  description: For assessing quality of life and vulvovaginal symptoms in women. Using "Absolutely not", "A little", "Some", "Very", "Extremely" to indicate the severity of symptoms
  measure: The detection rate of vaginal secretions of Gardnerella vaginalis, Lactobacillus janus, Lactobacillus garciae, Lactobacillus curvatus, Lactobacillus inertus, Lactobacillus chimaerae, Prevotella spp. and Streptococcus spp;
  time frame: 1year
  description: Detection of target flora in vaginal secretions using qPCR. Reflecting changes in vaginal microecology.
  measure: Serum concentrations of estrone, estradiol and oestrogen binding protein
  time frame: 1 year
  description: Testing serum hormone levels
  arm group label: C1, C2 dosing group
  arm group type: Experimental
  description: C1 and C2 dosing groups: The drug is administered on the day of the C1 and C2 chemotherapy cycles for 10 days, washing the vulva and placing the drug deep into the vagina, once a night, 1 capsules each time.
  arm group label: C3, C4 dosing group
  arm group type: Experimental
  description: C3 and C4 dosing groups: The drug is given on the day of the C3 and C4 chemotherapy cycles and is administered for 10 days. The drug is placed deep into the vagina after washing the vulva, once a night, 1 capsules each time.
  intervention type: Drug
  intervention name: Vaginal Lactobacillus capsules
  description: This product is a micro-ecological preparation made from live Lactobacillus and is used for the treatment of vaginosis caused by disorders of the flora.
  arm group label: C1, C2 dosing group
  arm group label: C3, C4 dosing group
  other name: Ding Jun Sheng
  criteria: 
  gender: Female
  minimum age: 18 Years
  maximum age: 45 Years
  healthy volunteers: No
  last name: Jue Wang, MD
  role: Study Director
  affiliation: The First Affiliated Hospital with Nanjing Medical University
  last name: Ran Zheng
  phone: 008615705227155
  email: 15705227155@163.com
  last name: Jue Wang, MD
  phone: 008618061695508
  email: wangjue200011@njmu.edu.cn
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: The First Affiliated Hospital with Nanjing Medical University
  investigator full name: Jue Wang
  investigator title: Prof.
  mesh term: Breast Neoplasms
  mesh term: Atrophy
  sharing ipd: No