<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/NCT02249325</url>
  </required_header>
  <id_info>
    <org_study_id>HR-2090</org_study_id>
    <nct_id>NCT02249325</nct_id>
  </id_info>
  <brief_title>Quasi Experiment of Prenatal Probiotics Against Group B Streptococcus Colonization</brief_title>
  <official_title>Effects of Probiotic Use During Pregnancy on Lactobacillus and Group B Streptococcus Vaginal Colonization: A Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Marquette University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Aurora Health Care</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Wisconsin, Madison</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Marquette University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This pilot quasi experiment was designed to determine the feasibility of a randomized&#xD;
      controlled trial of the oral probiotic combination of Florajen3 (&gt;7.5 x109 L. acidophilus,&#xD;
      &gt;6.0 x109. B. lactis, and &gt;1.5 x109 B. longum) taken orally once daily beginning at 28 weeks&#xD;
      gestation, against placebo, to reduce the colonization of group B Streptococcus at 36 weeks.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Methods&#xD;
&#xD;
      A non-blinded, open-label, quasi-experimental design was approved by the Institutional Review&#xD;
      Boards of three institutions (two universities and the clinical research site). The study&#xD;
      setting was a large Certified Nurse-Midwife (subsequently referred to as midwife) clinical&#xD;
      practice serving a culturally and economically diverse urban population in the Midwest region&#xD;
      of the USA.&#xD;
&#xD;
      Participants Women self-selected to participate in screening and informed consent procedures&#xD;
      done by the first two authors. The following inclusion criteria were used at study&#xD;
      enrollment: low risk (no obstetric, fetal, medical or genetic risk factors), adult (≥18 years&#xD;
      of age), pregnant at 28 ± 2 weeks gestation, able to speak and write English, and expressing&#xD;
      willingness to participate in the study intervention (oral probiotic) and data collection&#xD;
      (vaginal and rectal swabs, questionnaires).&#xD;
&#xD;
      A convenience sample of 20 healthy pregnant participants was sought. Following informed&#xD;
      consent, the first 10 subjects were assigned to the experimental group. Nonrandom assignment&#xD;
      was used to assure that the 10 experimental group participants were enrolled while remaining&#xD;
      within funding, and time constraints. After enrolling the experimental group, the next ten&#xD;
      women were assigned to the control group.&#xD;
&#xD;
      Intervention&#xD;
&#xD;
      The study intervention consisted of one capsule of Florajen3 (previously described) orally&#xD;
      each day. Florajen3 meets the internationally established probiotic criteria (FAO/WHO, 2001).&#xD;
      The probiotics contained in Florajen3 are non-spore-forming, lactose- and&#xD;
      hydrogen-peroxide-producing bacteria. The manufacturer recommends refrigeration to maintain&#xD;
      maximum potency. As part of the preparation for this study, a sample of Florajen3 was left&#xD;
      unrefrigerated for a period of 6 weeks and appropriate colony counts were sustained.&#xD;
      Therefore for the purpose of the study, the participants in the experimental group were&#xD;
      allowed to leave the probiotic unrefrigerated in an effort to improve daily compliance.&#xD;
      Experimental group study participants were made aware of the probiotic brand used (open&#xD;
      label) as the intervention.&#xD;
&#xD;
      Further, the current state of knowledge about prenatal probiotics, including potentially rare&#xD;
      side effects, were discussed at length using a 10-page informed consent document. The&#xD;
      Florajen3 was placed in a study bottle equipped with an electronic cap monitoring system&#xD;
      (MEMS ®AARDEX), designed to record each time the bottle was opened by the participant. Each&#xD;
      opening of the cap bottle equipped with this system is recorded on a microchip. The number of&#xD;
      openings are retrievable via computer software when the bottle caps are returned.&#xD;
      Researchers, midwives, and participants were aware of group assignment. The control group&#xD;
      participants did not receive a placebo.&#xD;
&#xD;
      Procedures&#xD;
&#xD;
      Midwife prenatal care providers and staff were oriented to the study data collection&#xD;
      procedures. Study data were collected at three points during routine prenatal visits with&#xD;
      each participant's midwife (28±2 weeks, 32±2 weeks, and 36±2 weeks gestation). The study was&#xD;
      considered completed at the 36±2 weeks gestation visit. All participants received&#xD;
      compensation at the completion of 2 study visits; 25 USD at 32±2 weeks and 75 USD at 36±2&#xD;
      weeks gestation. Probiotic group participants were offered a supply of probiotics for the&#xD;
      remainder of pregnancy.&#xD;
&#xD;
      The midwife prenatal provider collected demographic information (birth date, race, and&#xD;
      gestational age), and the vaginal and rectal swabs for GBS and wet mount, using accepted&#xD;
      criteria to identify the vaginal pH and the presence of normal flora and/or pathogens. The&#xD;
      wet mounts were examined microscopically by each midwife using standardized wet mount&#xD;
      diagnostic procedures with normal saline and potassium hydroxide and documented in a standard&#xD;
      format. Participants completed a brief questionnaire at each study visit that asked them to&#xD;
      describe yogurt ingestion, sexual activity (frequency and type), and vaginal cleansing&#xD;
      practices (if used) in the past week; these were considered potential confounding variables.&#xD;
      The participants were also asked if these practices were typical for them, and if not, how&#xD;
      they were atypical. Women in the experimental group were asked to report any side effects&#xD;
      that they attributed to the probiotics by notifying their midwife immediately, if necessary,&#xD;
      and then also noting the information on the study questionnaire. As part of routine prenatal&#xD;
      care, the CDC-required GBS vaginal to rectal swab was collected by each participant's midwife&#xD;
      and sent to the hospital laboratory between the 35 and 37 week visit. This was the only&#xD;
      result that determined the need for IAP.&#xD;
&#xD;
      Researchers oversaw data collection and sample packaging. Participants were asked to return&#xD;
      their probiotic bottles at each study visit and the Florajen3 capsules were replaced with a&#xD;
      fresh supply. This gave the researchers the opportunity to notify the laboratory to record&#xD;
      the date for later evaluation of the electronic cap monitoring results and conduct pill&#xD;
      counts as an additional means to monitor women's responses to study participation, as well as&#xD;
      probiotic adherence at each study visit. The vaginal and rectal swabs were placed on ice,&#xD;
      packaged according to accepted procedures for human specimen handling, and shipped overnight&#xD;
      to the laboratory of the final author, located 80 miles from the study site, for processing&#xD;
      and analysis.&#xD;
&#xD;
      Laboratory Analysis Upon receipt at the laboratory, the vaginal and rectal swabs were&#xD;
      processed for quantitative colony counts of GBS. Polymerase chain reaction (PCR) was&#xD;
      performed to determine whether bacteria isolated were the same as those in Florajen3. If&#xD;
      positive for PCR, pulsed field gel electrophoresis (PFGE) would be performed to confirm the&#xD;
      strain identity.&#xD;
&#xD;
      These results were for research purposes only and were not available to the practicing&#xD;
      midwives.&#xD;
&#xD;
      The routine CDC-recommended prenatal GBS vaginal to rectal swabs were analyzed at the&#xD;
      hospital laboratory, using a culture based method in which a threshold for GBS positive&#xD;
      results is considered greater than 102 colony forming units (CFU) per swab. These results&#xD;
      determined the need for IAP and were available to the midwives for management during labor.&#xD;
&#xD;
      Statistical Analysis&#xD;
&#xD;
      Demographics, the study variables, and laboratory data were entered into and analyzed with a&#xD;
      statistical software package. Descriptive statistics, Confidence Intervals, Chi-squares,&#xD;
      T-tests, and correlations were used for analysis. Data were compared between subjects at each&#xD;
      study visit and between groups at each data collection point. The qualitative prenatal GBS&#xD;
      culture results (positive or negative) from the hospital laboratory were compared to the&#xD;
      quantitative vaginal and rectal GBS study results, adherence data, and confounding variables&#xD;
      (yogurt ingestion, sexual activity, and vaginal cleansing practices).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2011</start_date>
  <completion_date type="Actual">June 2013</completion_date>
  <primary_completion_date type="Actual">October 2011</primary_completion_date>
  <phase>N/A</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>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Prenatal group B Streptococcus Colonization</measure>
    <time_frame>36 weeks gestation</time_frame>
    <description>Routine prenatal GBS cultures were collected on all study participants at 35-37 weeks gestation as per the 2010 CDC GBS prevention guidelines. Only this result was use to determined the need for intrapartum antibiotic prophylaxis.&#xD;
All study participants received separate vaginal and rectal GBS culture swabs that were analyzed quantitatively for GBS/swab in Colony Forming Units (CFUs). These results were blind to the prenatal care providers.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Recruitment and retention of a diverse sample.</measure>
    <time_frame>28 to 36 weeks gestation</time_frame>
    <description>The clinical setting was a large, urban Nurse-Midwifery practice that serves an ethnically and economically diverse group of women.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Pregnancy</condition>
  <arm_group>
    <arm_group_label>Probiotic dietary supplement</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Florajen3 oral probiotic (&gt;7.5 x10^9 L. acidophilus, &gt;6.0 x10^9 .B. lactis, and &gt;1.5 x10^9 B .longum) taken daily beginning at 28 weeks gestation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Women in the comparison group did not take a placebo.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Probiotic dietary supplement</intervention_name>
    <description>Florajen3 is a commercially available probiotic supplement containing three bacteria of human origin (&gt;7.5 x10^9 L. acidophilus, &gt;6.0 x10^9 .B. lactis, and &gt;1.5 x10^9 B .longum). Once capsule was administered daily by mouth from 28 through 36 weeks gestation.</description>
    <arm_group_label>Probiotic dietary supplement</arm_group_label>
    <other_name>Florajen3 Probiotic</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Low risk pregnancy (no obstetric, fetal, medical or genetic risk factors)&#xD;
&#xD;
          -  Adult (≥18 years of age)&#xD;
&#xD;
          -  Pregnant at 28 ± 2 weeks gestation&#xD;
&#xD;
          -  Able to speak and write English&#xD;
&#xD;
          -  Willingness to participate in the study intervention (oral probiotic) and data&#xD;
             collection (including vaginal and rectal swabs and questionnaires)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant women with obstetric, fetal, medical, or genetic risk factors.&#xD;
&#xD;
          -  &lt;18 years of age&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lisa C Hanson, PhD, CNM</last_name>
    <role>Principal Investigator</role>
    <affiliation>Marquette University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Aurora Healthcare</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53201-0342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Hanson L, Vandevusse L, Duster M, Warrack S, Safdar N. Feasibility of oral prenatal probiotics against maternal group B Streptococcus vaginal and rectal colonization. J Obstet Gynecol Neonatal Nurs. 2014 May-Jun;43(3):294-304. doi: 10.1111/1552-6909.12308. Epub 2014 Apr 22.</citation>
    <PMID>24754328</PMID>
  </results_reference>
  <verification_date>October 2014</verification_date>
  <study_first_submitted>June 3, 2013</study_first_submitted>
  <study_first_submitted_qc>September 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>October 3, 2014</last_update_submitted>
  <last_update_submitted_qc>October 3, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 7, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Marquette University</investigator_affiliation>
    <investigator_full_name>Lisa Hanson</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>group B Streptococcus colonization</keyword>
  <keyword>Probiotic</keyword>
  <keyword>Pregnancy</keyword>
  <pending_results>
    <submitted>February 23, 2023</submitted>
  </pending_results>
  <!-- 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/NCT02249325
org study id: HR-2090
nct id: NCT02249325
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
This pilot quasi experiment was designed to determine the feasibility of a randomized
      controlled trial of the oral probiotic combination of Florajen3 (>7.5 x109 L. acidophilus,
      >6.0 x109. B. lactis, and >1.5 x109 B. longum) taken orally once daily beginning at 28 weeks
      gestation, against placebo, to reduce the colonization of group B Streptococcus at 36 weeks.
Methods

      A non-blinded, open-label, quasi-experimental design was approved by the Institutional Review
      Boards of three institutions (two universities and the clinical research site). The study
      setting was a large Certified Nurse-Midwife (subsequently referred to as midwife) clinical
      practice serving a culturally and economically diverse urban population in the Midwest region
      of the USA.

      Participants Women self-selected to participate in screening and informed consent procedures
      done by the first two authors. The following inclusion criteria were used at study
      enrollment: low risk (no obstetric, fetal, medical or genetic risk factors), adult (≥18 years
      of age), pregnant at 28 ± 2 weeks gestation, able to speak and write English, and expressing
      willingness to participate in the study intervention (oral probiotic) and data collection
      (vaginal and rectal swabs, questionnaires).

      A convenience sample of 20 healthy pregnant participants was sought. Following informed
      consent, the first 10 subjects were assigned to the experimental group. Nonrandom assignment
      was used to assure that the 10 experimental group participants were enrolled while remaining
      within funding, and time constraints. After enrolling the experimental group, the next ten
      women were assigned to the control group.

      Intervention

      The study intervention consisted of one capsule of Florajen3 (previously described) orally
      each day. Florajen3 meets the internationally established probiotic criteria (FAO/WHO, 2001).
      The probiotics contained in Florajen3 are non-spore-forming, lactose- and
      hydrogen-peroxide-producing bacteria. The manufacturer recommends refrigeration to maintain
      maximum potency. As part of the preparation for this study, a sample of Florajen3 was left
      unrefrigerated for a period of 6 weeks and appropriate colony counts were sustained.
      Therefore for the purpose of the study, the participants in the experimental group were
      allowed to leave the probiotic unrefrigerated in an effort to improve daily compliance.
      Experimental group study participants were made aware of the probiotic brand used (open
      label) as the intervention.

      Further, the current state of knowledge about prenatal probiotics, including potentially rare
      side effects, were discussed at length using a 10-page informed consent document. The
      Florajen3 was placed in a study bottle equipped with an electronic cap monitoring system
      (MEMS ®AARDEX), designed to record each time the bottle was opened by the participant. Each
      opening of the cap bottle equipped with this system is recorded on a microchip. The number of
      openings are retrievable via computer software when the bottle caps are returned.
      Researchers, midwives, and participants were aware of group assignment. The control group
      participants did not receive a placebo.

      Procedures

      Midwife prenatal care providers and staff were oriented to the study data collection
      procedures. Study data were collected at three points during routine prenatal visits with
      each participant's midwife (28±2 weeks, 32±2 weeks, and 36±2 weeks gestation). The study was
      considered completed at the 36±2 weeks gestation visit. All participants received
      compensation at the completion of 2 study visits; 25 USD at 32±2 weeks and 75 USD at 36±2
      weeks gestation. Probiotic group participants were offered a supply of probiotics for the
      remainder of pregnancy.

      The midwife prenatal provider collected demographic information (birth date, race, and
      gestational age), and the vaginal and rectal swabs for GBS and wet mount, using accepted
      criteria to identify the vaginal pH and the presence of normal flora and/or pathogens. The
      wet mounts were examined microscopically by each midwife using standardized wet mount
      diagnostic procedures with normal saline and potassium hydroxide and documented in a standard
      format. Participants completed a brief questionnaire at each study visit that asked them to
      describe yogurt ingestion, sexual activity (frequency and type), and vaginal cleansing
      practices (if used) in the past week; these were considered potential confounding variables.
      The participants were also asked if these practices were typical for them, and if not, how
      they were atypical. Women in the experimental group were asked to report any side effects
      that they attributed to the probiotics by notifying their midwife immediately, if necessary,
      and then also noting the information on the study questionnaire. As part of routine prenatal
      care, the CDC-required GBS vaginal to rectal swab was collected by each participant's midwife
      and sent to the hospital laboratory between the 35 and 37 week visit. This was the only
      result that determined the need for IAP.

      Researchers oversaw data collection and sample packaging. Participants were asked to return
      their probiotic bottles at each study visit and the Florajen3 capsules were replaced with a
      fresh supply. This gave the researchers the opportunity to notify the laboratory to record
      the date for later evaluation of the electronic cap monitoring results and conduct pill
      counts as an additional means to monitor women's responses to study participation, as well as
      probiotic adherence at each study visit. The vaginal and rectal swabs were placed on ice,
      packaged according to accepted procedures for human specimen handling, and shipped overnight
      to the laboratory of the final author, located 80 miles from the study site, for processing
      and analysis.

      Laboratory Analysis Upon receipt at the laboratory, the vaginal and rectal swabs were
      processed for quantitative colony counts of GBS. Polymerase chain reaction (PCR) was
      performed to determine whether bacteria isolated were the same as those in Florajen3. If
      positive for PCR, pulsed field gel electrophoresis (PFGE) would be performed to confirm the
      strain identity.

      These results were for research purposes only and were not available to the practicing
      midwives.

      The routine CDC-recommended prenatal GBS vaginal to rectal swabs were analyzed at the
      hospital laboratory, using a culture based method in which a threshold for GBS positive
      results is considered greater than 102 colony forming units (CFU) per swab. These results
      determined the need for IAP and were available to the midwives for management during labor.

      Statistical Analysis

      Demographics, the study variables, and laboratory data were entered into and analyzed with a
      statistical software package. Descriptive statistics, Confidence Intervals, Chi-squares,
      T-tests, and correlations were used for analysis. Data were compared between subjects at each
      study visit and between groups at each data collection point. The qualitative prenatal GBS
      culture results (positive or negative) from the hospital laboratory were compared to the
      quantitative vaginal and rectal GBS study results, adherence data, and confounding variables
      (yogurt ingestion, sexual activity, and vaginal cleansing practices).
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Prenatal group B Streptococcus Colonization
time frame: 36 weeks gestation
description: Routine prenatal GBS cultures were collected on all study participants at 35-37 weeks gestation as per the 2010 CDC GBS prevention guidelines. Only this result was use to determined the need for intrapartum antibiotic prophylaxis.
All study participants received separate vaginal and rectal GBS culture swabs that were analyzed quantitatively for GBS/swab in Colony Forming Units (CFUs). These results were blind to the prenatal care providers.
measure: Recruitment and retention of a diverse sample.
time frame: 28 to 36 weeks gestation
description: The clinical setting was a large, urban Nurse-Midwifery practice that serves an ethnically and economically diverse group of women.
arm group label: Probiotic dietary supplement
arm group type: Experimental
description: Florajen3 oral probiotic (>7.5 x10^9 L. acidophilus, >6.0 x10^9 .B. lactis, and >1.5 x10^9 B .longum) taken daily beginning at 28 weeks gestation.
arm group label: Placebo
arm group type: No Intervention
description: Women in the comparison group did not take a placebo.
intervention type: Dietary Supplement
intervention name: Probiotic dietary supplement
description: Florajen3 is a commercially available probiotic supplement containing three bacteria of human origin (>7.5 x10^9 L. acidophilus, >6.0 x10^9 .B. lactis, and >1.5 x10^9 B .longum). Once capsule was administered daily by mouth from 28 through 36 weeks gestation.
arm group label: Probiotic dietary supplement
other name: Florajen3 Probiotic
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Lisa C Hanson, PhD, CNM
role: Principal Investigator
affiliation: Marquette University
facility: 
country: United States
citation: Hanson L, Vandevusse L, Duster M, Warrack S, Safdar N. Feasibility of oral prenatal probiotics against maternal group B Streptococcus vaginal and rectal colonization. J Obstet Gynecol Neonatal Nurs. 2014 May-Jun;43(3):294-304. doi: 10.1111/1552-6909.12308. Epub 2014 Apr 22.
PMID: 24754328
responsible party type: Principal Investigator
investigator affiliation: Marquette University
investigator full name: Lisa Hanson
investigator title: Associate Professor
submitted: February 23, 2023