<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/NCT01697683</url>
  </required_header>
  <id_info>
    <org_study_id>08-0005-A</org_study_id>
    <nct_id>NCT01697683</nct_id>
  </id_info>
  <brief_title>Probiotic Therapy for the Reversal of Bacterial Vaginosis in Pregnancy</brief_title>
  <acronym>ProVIP</acronym>
  <official_title>Probiotic Therapy for the Reversal of Bacterial Vaginosis in Pregnancy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mount Sinai Hospital, Canada</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Unity Health Toronto</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Mount Sinai Hospital, Canada</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will add to the current knowledge and literature on the ability of an oral&#xD;
      lactobacilli preparation to return the vaginal flora to a normal state in pregnant women. The&#xD;
      results will potentially serve as the basis for a multi-centre Phase III randomized clinical&#xD;
      trial to determine the efficacy of this treatment in preventing preterm birth.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Preterm birth continues to provide the greatest challenge in perinatal health care in the&#xD;
      developed world. It is a syndrome involving multiple causes and arises from a number of&#xD;
      social, psychological, and biological determinants. It has been estimated that intrauterine&#xD;
      infection accounts for at least 25-40% of spontaneous preterm births, with infection being&#xD;
      the primary cause of extreme prematurity. Because infection-mediated preterm delivery mainly&#xD;
      occurs in younger gestational ages (less than 28 weeks), these extremely premature babies not&#xD;
      only have the risks associated with being born early, but are also likely to have severe&#xD;
      morbidities associated with infection. Bacterial vaginosis (BV) is defined as a loss or&#xD;
      significant depletion of lactobacilli coupled with an overgrowth of pathogenic bacteria and&#xD;
      an increase in vaginal pH (&gt;4.5). BV is common and occurs in 20% of the general female&#xD;
      population, often without symptoms and is associated with a 40% increased risk of preterm&#xD;
      birth. The clinical finding that lactobacilli is the dominant microbe in the vagina of women&#xD;
      with a healthy pregnancy and full term delivery, supports the association of this species&#xD;
      with a healthy pregnancy. BV is associated with an elevation of cervico-vaginal&#xD;
      pro-inflammatory cytokines including IL-1β and IL-8 that are also associated with preterm&#xD;
      labour; initiating the inflammatory cascade of events involved in labour may be the mechanism&#xD;
      by which BV triggers preterm birth. However, not all women with BV will deliver preterm&#xD;
      suggesting that variations in genetic susceptibility may underlie the host response to the&#xD;
      presence of BV and the risk for preterm birth. Antibiotic therapy is the current treatment&#xD;
      for BV, but the extent to which antibiotics can prevent preterm birth in women with BV&#xD;
      remains somewhat uncertain, with conflicting results published in the literature. The&#xD;
      apparent ineffective nature of antibiotic therapy, perhaps due to a lack of regrowth of&#xD;
      lactobacilli following treatment, and the possibility that the pathogens have already induced&#xD;
      inflammatory processes that will eventually induce preterm birth, emphasizes the need to&#xD;
      continue to investigate the role of microbes during pregnancy. Probiotics have been suggested&#xD;
      as an alternative to antibiotic therapy in restoring vaginal lactobacilli and reversing BV.&#xD;
      The study seeks to determine whether Lactobacillus rhamnosus, GR-1 and Lactobacillus reuteri,&#xD;
      RC-14 when administered to pregnant women diagnosed with bacterial vaginosis or intermediate&#xD;
      flora will reverse the condition leading to a decrease in the inflammatory mediators involved&#xD;
      in the cascade of infection/inflammation-mediated preterm birth.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>May 2012</start_date>
  <completion_date type="Actual">March 2014</completion_date>
  <primary_completion_date type="Actual">March 2014</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Microbial DNA profile</measure>
    <time_frame>At 28 and at 35 weeks gestation</time_frame>
    <description>A change in the Vaginal Microbial DNA profile</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Microbial function</measure>
    <time_frame>At 28 and at 35 weeks gestation</time_frame>
    <description>A change in microbial function as measured by RNA transcriptomics</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">86</enrollment>
  <condition>Pregnant Women Who Test Positive for Bacterial Vaginosis</condition>
  <arm_group>
    <arm_group_label>Probiotic Rhamnosus Lactobacilli</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Sugar pill</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Probiotic Lactobacilli</intervention_name>
    <description>Two capsules per day containing either probiotic lactobacilli or placebo for 12 weeks</description>
    <arm_group_label>Probiotic Rhamnosus Lactobacilli</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Sugar pill</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  pregnant women prior to 17 weeks gestation&#xD;
&#xD;
          -  singleton pregnancy&#xD;
&#xD;
          -  over 18 years of age&#xD;
&#xD;
          -  able to provide informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  multifetal pregnancies (twins, triplets, etc)&#xD;
&#xD;
          -  fetal complications (congenital anomaly, chromosomal abnormality)&#xD;
&#xD;
          -  maternal history of previous preterm birth or second trimester loss&#xD;
&#xD;
          -  significant maternal medical or surgical complications (eg. hypertension, diabetes)&#xD;
&#xD;
          -  less than 18 years of age&#xD;
&#xD;
          -  unable to provide informed consent&#xD;
&#xD;
          -  HIV Positive&#xD;
&#xD;
          -  Immuno-compromised&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alan Bocking, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>MOUNT SINAI HOSPITAL</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mount Sinai Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1X5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>March 2014</verification_date>
  <study_first_submitted>September 28, 2012</study_first_submitted>
  <study_first_submitted_qc>October 1, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 2, 2012</study_first_posted>
  <last_update_submitted>March 20, 2014</last_update_submitted>
  <last_update_submitted_qc>March 20, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 24, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaginosis, Bacterial</mesh_term>
    <mesh_term>Vaginal Diseases</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT01697683
org study id: 08-0005-A
nct id: NCT01697683
lead sponsor: 
collaborator: 
has dmc: Yes
This study will add to the current knowledge and literature on the ability of an oral
      lactobacilli preparation to return the vaginal flora to a normal state in pregnant women. The
      results will potentially serve as the basis for a multi-centre Phase III randomized clinical
      trial to determine the efficacy of this treatment in preventing preterm birth.
Preterm birth continues to provide the greatest challenge in perinatal health care in the
      developed world. It is a syndrome involving multiple causes and arises from a number of
      social, psychological, and biological determinants. It has been estimated that intrauterine
      infection accounts for at least 25-40% of spontaneous preterm births, with infection being
      the primary cause of extreme prematurity. Because infection-mediated preterm delivery mainly
      occurs in younger gestational ages (less than 28 weeks), these extremely premature babies not
      only have the risks associated with being born early, but are also likely to have severe
      morbidities associated with infection. Bacterial vaginosis (BV) is defined as a loss or
      significant depletion of lactobacilli coupled with an overgrowth of pathogenic bacteria and
      an increase in vaginal pH (>4.5). BV is common and occurs in 20% of the general female
      population, often without symptoms and is associated with a 40% increased risk of preterm
      birth. The clinical finding that lactobacilli is the dominant microbe in the vagina of women
      with a healthy pregnancy and full term delivery, supports the association of this species
      with a healthy pregnancy. BV is associated with an elevation of cervico-vaginal
      pro-inflammatory cytokines including IL-1β and IL-8 that are also associated with preterm
      labour; initiating the inflammatory cascade of events involved in labour may be the mechanism
      by which BV triggers preterm birth. However, not all women with BV will deliver preterm
      suggesting that variations in genetic susceptibility may underlie the host response to the
      presence of BV and the risk for preterm birth. Antibiotic therapy is the current treatment
      for BV, but the extent to which antibiotics can prevent preterm birth in women with BV
      remains somewhat uncertain, with conflicting results published in the literature. The
      apparent ineffective nature of antibiotic therapy, perhaps due to a lack of regrowth of
      lactobacilli following treatment, and the possibility that the pathogens have already induced
      inflammatory processes that will eventually induce preterm birth, emphasizes the need to
      continue to investigate the role of microbes during pregnancy. Probiotics have been suggested
      as an alternative to antibiotic therapy in restoring vaginal lactobacilli and reversing BV.
      The study seeks to determine whether Lactobacillus rhamnosus, GR-1 and Lactobacillus reuteri,
      RC-14 when administered to pregnant women diagnosed with bacterial vaginosis or intermediate
      flora will reverse the condition leading to a decrease in the inflammatory mediators involved
      in the cascade of infection/inflammation-mediated preterm birth.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Microbial DNA profile
time frame: At 28 and at 35 weeks gestation
description: A change in the Vaginal Microbial DNA profile
measure: Microbial function
time frame: At 28 and at 35 weeks gestation
description: A change in microbial function as measured by RNA transcriptomics
arm group label: Probiotic Rhamnosus Lactobacilli
arm group type: Active Comparator
arm group label: Sugar pill
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Probiotic Lactobacilli
description: Two capsules per day containing either probiotic lactobacilli or placebo for 12 weeks
arm group label: Probiotic Rhamnosus Lactobacilli
intervention type: Drug
intervention name: Placebo
arm group label: Sugar pill
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Alan Bocking, MD
role: Principal Investigator
affiliation: MOUNT SINAI HOSPITAL
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Vaginosis, Bacterial
mesh term: Vaginal Diseases