<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/NCT04471116</url>
  </required_header>
  <id_info>
    <org_study_id>FRED002</org_study_id>
    <nct_id>NCT04471116</nct_id>
  </id_info>
  <brief_title>Influence of Probiotics on the Vaginal Microbiota</brief_title>
  <official_title>Influence of OMNi-BiOTiC® FLORA Plus+ on the Vaginal Microbiome of Patients Suffering From Infertility</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kinderwunsch Institut GmbH</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Institut AllergoSan</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Kinderwunsch Institut GmbH</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study aims to assess the influence of a probiotic supplement (OMNi-BiOTiC® FLORA plus +)&#xD;
      on the vaginal microbiome composition of women suffering from infertility.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Infertility is a global phenomenon affecting around 186 millions of people worldwide. Many&#xD;
      circumstances have been identified to cause infertile conditions, with age being one of the&#xD;
      most limiting factors. However, in recent years the microbiome has gained importance in the&#xD;
      treatment of infertility and is considered as another important player to improve success&#xD;
      rate of reproductive medicine treatments like in-vitro-fertilization (IVF).&#xD;
&#xD;
      Within the female reproductive tract the dominance of Lactobacilli is associated with a&#xD;
      healthy vaginal microbial community in healthy reproductive-aged women. Since the microbiome&#xD;
      has gained so much importance, its influence in IVF treatments is still controversially&#xD;
      discussed. While some studies suggest a negative influence of vaginal dysbiosis on pregnancy&#xD;
      rates a current meta-analysis showed no association between abnormal vaginal flora and&#xD;
      conception rates following IVF treatment. One therapeutic approach is the administration of&#xD;
      beneficial microorganisms (probiotics), mainly Lactobacillus species. The supplementation of&#xD;
      exogenous lactobacilli strains has been suggested as cure for a dysbiotic vaginal flora to&#xD;
      re-establish healthy conditions and improving female fertility health.&#xD;
&#xD;
      Hence, in the present study we wanted to investigate the impact of 4 probiotic strains&#xD;
      (Lactobacillus crispatus LBV88, Lactobacillus rhamnosus LBV96, Lactobacillus gasseri LBV150N&#xD;
      and Lactobacillus jensenii LBV116) on the relative abundance of vaginal microbiata species in&#xD;
      women suffering from infertility.&#xD;
&#xD;
      80 infertile women suffering from infertility were included in the study within fertility&#xD;
      treatment. 40 patients with IVF / ICSI were examined (20 with OMNi-BiOTiC® FLORA plus +, 20&#xD;
      as a control) and 40 patients with IUI / VZO (20 with OMNi-BiOTiC® FLORA plus +, 20 as a&#xD;
      control). The control patients were selected from the routine patient collective of the&#xD;
      Kinderwunsch Institut Schenk GmbH and receive no treatment with probiotics or placebo.&#xD;
      Patients in the therapy group took 1 sachet of OMNi-BiOTiC® FLORA plus + (= 2 g) dissolved in&#xD;
      1/8 l of water once a day. Patients in the control group received no additional medication&#xD;
      for routine treatment. Patients were randomized after inclusion in the study (block&#xD;
      randomization).&#xD;
&#xD;
      On day 20 in the pre-cycle of hormonal stimulation, a vaginal smear sample was taken from the&#xD;
      patient. The investigator introduced a sterile swab (eSwabTM, Copan Diagnostics Inc., USA),&#xD;
      and took material from the mucosal surface. The eSwab was transferred to a sterile Falcon&#xD;
      tube, stored at -72 ° C and then handed over to the company biovis Diagnostik MVZ GmbH&#xD;
      (Germany) for 16s rRNA gene analysis. On day 20 in the stimulated cycle or subsequent cycle&#xD;
      of the fertility treatment, another vaginal smear sample was taken and also stored in a&#xD;
      sterile Falcon tube at -72 ° C.&#xD;
&#xD;
      The microbiota was determined using 16s rRNA gene analysis. The bacterial genomic DNA was&#xD;
      isolated from the samples and the region V3-V4 was sequenced (Nextera XT, DNA Library&#xD;
      Preparation Kit; Illumina MiSeq, Illumina, The Netherlands).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 30, 2018</start_date>
  <completion_date type="Actual">November 12, 2019</completion_date>
  <primary_completion_date type="Actual">July 19, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>vaginal microbiome</measure>
    <time_frame>1 month</time_frame>
    <description>The microbiota was determined using 16s rRNA gene analysis. The bacterial genomic DNA was isolated from the samples and the region V3-V4 was sequenced</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">80</enrollment>
  <condition>Vaginal Microbiome</condition>
  <arm_group>
    <arm_group_label>Therapy group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients in the therapy group took 1 sachet of OMNi-BiOTiC® FLORA plus + (= 2 g) dissolved in 1/8 l of water once a day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients in the control group received no additional medication.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>OMNi-BiOTiC® FLORA plus+</intervention_name>
    <description>OMNi-BiOTiC® FLORA plus + is a dietary supplement for the treatment of a disturbed vaginal flora (dysbiosis). The product combines probiotic bacterial strains with a special fiber mixture. The product contains the following strains: Lactobacillus crispatus LBV88, Lactobacillus rhamnosus LBV96, Lactobacillus gasseri LBV150N and Lactobacillus jensenii LBV116</description>
    <arm_group_label>Therapy group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patients with primary or secondary infertility&#xD;
&#xD;
          -  age between 18 and 40&#xD;
&#xD;
          -  signed informed consent&#xD;
&#xD;
          -  BMI between 19 and 29.9&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with severe, acute and / or chronic diseases&#xD;
&#xD;
          -  obesity&#xD;
&#xD;
          -  hirsutism&#xD;
&#xD;
          -  current intake of antibiotics&#xD;
&#xD;
          -  State after hysterectomy&#xD;
&#xD;
          -  Simultaneous use of other probiotics&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael Schenk, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Kinderwunsch Institut GmbH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Das Kinderwunsch Institut Schenk GmbH</name>
      <address>
        <city>Dobl</city>
        <state>Styria</state>
        <zip>8143</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <reference>
    <citation>Inhorn MC, Patrizio P. Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century. Hum Reprod Update. 2015 Jul-Aug;21(4):411-26. doi: 10.1093/humupd/dmv016. Epub 2015 Mar 22.</citation>
    <PMID>25801630</PMID>
  </reference>
  <reference>
    <citation>Moreno I, Codoner FM, Vilella F, Valbuena D, Martinez-Blanch JF, Jimenez-Almazan J, Alonso R, Alama P, Remohi J, Pellicer A, Ramon D, Simon C. Evidence that the endometrial microbiota has an effect on implantation success or failure. Am J Obstet Gynecol. 2016 Dec;215(6):684-703. doi: 10.1016/j.ajog.2016.09.075. Epub 2016 Oct 4.</citation>
    <PMID>27717732</PMID>
  </reference>
  <reference>
    <citation>Miles SM, Hardy BL, Merrell DS. Investigation of the microbiota of the reproductive tract in women undergoing a total hysterectomy and bilateral salpingo-oopherectomy. Fertil Steril. 2017 Mar;107(3):813-820.e1. doi: 10.1016/j.fertnstert.2016.11.028. Epub 2017 Jan 6.</citation>
    <PMID>28069180</PMID>
  </reference>
  <reference>
    <citation>Haahr T, Jensen JS, Thomsen L, Duus L, Rygaard K, Humaidan P. Abnormal vaginal microbiota may be associated with poor reproductive outcomes: a prospective study in IVF patients. Hum Reprod. 2016 Apr;31(4):795-803. doi: 10.1093/humrep/dew026. Epub 2016 Feb 23.</citation>
    <PMID>26911864</PMID>
  </reference>
  <reference>
    <citation>van Oostrum N, De Sutter P, Meys J, Verstraelen H. Risks associated with bacterial vaginosis in infertility patients: a systematic review and meta-analysis. Hum Reprod. 2013 Jul;28(7):1809-15. doi: 10.1093/humrep/det096. Epub 2013 Mar 29.</citation>
    <PMID>23543384</PMID>
  </reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 10, 2020</study_first_submitted>
  <study_first_submitted_qc>July 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 15, 2020</study_first_posted>
  <last_update_submitted>July 14, 2020</last_update_submitted>
  <last_update_submitted_qc>July 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>infertility</keyword>
  <keyword>dysbiosis</keyword>
  <keyword>probiotics</keyword>
  <keyword>Lactobacillus</keyword>
  <keyword>microbiome</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infertility</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Data will be available within a publication of the study</ipd_description>
  </patient_data>
  <!-- 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/NCT04471116
org study id: FRED002
nct id: NCT04471116
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The study aims to assess the influence of a probiotic supplement (OMNi-BiOTiC® FLORA plus +)
      on the vaginal microbiome composition of women suffering from infertility.
Infertility is a global phenomenon affecting around 186 millions of people worldwide. Many
      circumstances have been identified to cause infertile conditions, with age being one of the
      most limiting factors. However, in recent years the microbiome has gained importance in the
      treatment of infertility and is considered as another important player to improve success
      rate of reproductive medicine treatments like in-vitro-fertilization (IVF).

      Within the female reproductive tract the dominance of Lactobacilli is associated with a
      healthy vaginal microbial community in healthy reproductive-aged women. Since the microbiome
      has gained so much importance, its influence in IVF treatments is still controversially
      discussed. While some studies suggest a negative influence of vaginal dysbiosis on pregnancy
      rates a current meta-analysis showed no association between abnormal vaginal flora and
      conception rates following IVF treatment. One therapeutic approach is the administration of
      beneficial microorganisms (probiotics), mainly Lactobacillus species. The supplementation of
      exogenous lactobacilli strains has been suggested as cure for a dysbiotic vaginal flora to
      re-establish healthy conditions and improving female fertility health.

      Hence, in the present study we wanted to investigate the impact of 4 probiotic strains
      (Lactobacillus crispatus LBV88, Lactobacillus rhamnosus LBV96, Lactobacillus gasseri LBV150N
      and Lactobacillus jensenii LBV116) on the relative abundance of vaginal microbiata species in
      women suffering from infertility.

      80 infertile women suffering from infertility were included in the study within fertility
      treatment. 40 patients with IVF / ICSI were examined (20 with OMNi-BiOTiC® FLORA plus +, 20
      as a control) and 40 patients with IUI / VZO (20 with OMNi-BiOTiC® FLORA plus +, 20 as a
      control). The control patients were selected from the routine patient collective of the
      Kinderwunsch Institut Schenk GmbH and receive no treatment with probiotics or placebo.
      Patients in the therapy group took 1 sachet of OMNi-BiOTiC® FLORA plus + (= 2 g) dissolved in
      1/8 l of water once a day. Patients in the control group received no additional medication
      for routine treatment. Patients were randomized after inclusion in the study (block
      randomization).

      On day 20 in the pre-cycle of hormonal stimulation, a vaginal smear sample was taken from the
      patient. The investigator introduced a sterile swab (eSwabTM, Copan Diagnostics Inc., USA),
      and took material from the mucosal surface. The eSwab was transferred to a sterile Falcon
      tube, stored at -72 ° C and then handed over to the company biovis Diagnostik MVZ GmbH
      (Germany) for 16s rRNA gene analysis. On day 20 in the stimulated cycle or subsequent cycle
      of the fertility treatment, another vaginal smear sample was taken and also stored in a
      sterile Falcon tube at -72 ° C.

      The microbiota was determined using 16s rRNA gene analysis. The bacterial genomic DNA was
      isolated from the samples and the region V3-V4 was sequenced (Nextera XT, DNA Library
      Preparation Kit; Illumina MiSeq, Illumina, The Netherlands).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: vaginal microbiome
time frame: 1 month
description: The microbiota was determined using 16s rRNA gene analysis. The bacterial genomic DNA was isolated from the samples and the region V3-V4 was sequenced
arm group label: Therapy group
arm group type: Active Comparator
description: Patients in the therapy group took 1 sachet of OMNi-BiOTiC® FLORA plus + (= 2 g) dissolved in 1/8 l of water once a day
arm group label: Control group
arm group type: No Intervention
description: Patients in the control group received no additional medication.
intervention type: Dietary Supplement
intervention name: OMNi-BiOTiC® FLORA plus+
description: OMNi-BiOTiC® FLORA plus + is a dietary supplement for the treatment of a disturbed vaginal flora (dysbiosis). The product combines probiotic bacterial strains with a special fiber mixture. The product contains the following strains: Lactobacillus crispatus LBV88, Lactobacillus rhamnosus LBV96, Lactobacillus gasseri LBV150N and Lactobacillus jensenii LBV116
arm group label: Therapy group
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: No
last name: Michael Schenk, MD
role: Principal Investigator
affiliation: Kinderwunsch Institut GmbH
facility: 
country: Austria
citation: Inhorn MC, Patrizio P. Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century. Hum Reprod Update. 2015 Jul-Aug;21(4):411-26. doi: 10.1093/humupd/dmv016. Epub 2015 Mar 22.
PMID: 25801630
citation: Moreno I, Codoner FM, Vilella F, Valbuena D, Martinez-Blanch JF, Jimenez-Almazan J, Alonso R, Alama P, Remohi J, Pellicer A, Ramon D, Simon C. Evidence that the endometrial microbiota has an effect on implantation success or failure. Am J Obstet Gynecol. 2016 Dec;215(6):684-703. doi: 10.1016/j.ajog.2016.09.075. Epub 2016 Oct 4.
PMID: 27717732
citation: Miles SM, Hardy BL, Merrell DS. Investigation of the microbiota of the reproductive tract in women undergoing a total hysterectomy and bilateral salpingo-oopherectomy. Fertil Steril. 2017 Mar;107(3):813-820.e1. doi: 10.1016/j.fertnstert.2016.11.028. Epub 2017 Jan 6.
PMID: 28069180
citation: Haahr T, Jensen JS, Thomsen L, Duus L, Rygaard K, Humaidan P. Abnormal vaginal microbiota may be associated with poor reproductive outcomes: a prospective study in IVF patients. Hum Reprod. 2016 Apr;31(4):795-803. doi: 10.1093/humrep/dew026. Epub 2016 Feb 23.
PMID: 26911864
citation: van Oostrum N, De Sutter P, Meys J, Verstraelen H. Risks associated with bacterial vaginosis in infertility patients: a systematic review and meta-analysis. Hum Reprod. 2013 Jul;28(7):1809-15. doi: 10.1093/humrep/det096. Epub 2013 Mar 29.
PMID: 23543384
responsible party type: Sponsor
mesh term: Infertility
sharing ipd: No
ipd description: Data will be available within a publication of the study