<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/NCT03250208</url>
  </required_header>
  <id_info>
    <org_study_id>209830</org_study_id>
    <nct_id>NCT03250208</nct_id>
  </id_info>
  <brief_title>Probiotics Effect on the Female Urinary Microbiome ProFUM Trial (Probiotics Effect on the Female Urinary Microbiome)</brief_title>
  <acronym>ProFUM</acronym>
  <official_title>Probiotics and the Female Urinary Microbiome ProFUM Trial (Probiotics Effect on the Female Urinary Microbiome)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Loyola University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Loyola University</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 will enroll healthy pre-menopausal female volunteers in the community. These&#xD;
      subjects will act as their own controls. The subjects will collect voided urine and&#xD;
      peri-urethral swab specimens daily for several months. They will also be asked to collect&#xD;
      vaginal and peri-rectal swab specimens at various time points. Subjects will document various&#xD;
      lifestyle variables daily. During the middle of the study, subjects will be randomized to&#xD;
      probiotic vs placebo. Using bacterial culture and 16S rRNA gene sequencing, the study will&#xD;
      measure the bacterial populations of several anatomic sites longitudinally: voided urine,&#xD;
      peri-urethra, vagina, and peri-rectal. The study hypothesizes that oral probiotic usage will&#xD;
      alter the bacterial populations and ratio of Lactobacillus to E. coli within each of these&#xD;
      sites. Additionally, the study hypothesizes that the changes within each site will occur&#xD;
      first in the rectum (i.e. GI tract), followed by the vagina, and then the urethra and&#xD;
      bladder.&#xD;
&#xD;
      Using the prospective design of daily sampling and lifestyle variable documentation, the&#xD;
      study may be able to identify possible influences on microbiome stability within the sampled&#xD;
      sites. The lifestyle variables recorded include: diet, medication usage, menstruation, sexual&#xD;
      activity, and alcohol consumption.&#xD;
&#xD;
      This pilot study will establish the variance of the outcome variables among healthy women and&#xD;
      confirm the emergence of the probiotic with the recommended dose. With this information,&#xD;
      future researchers will be able to calculate the power needed for a larger randomized trial.&#xD;
      This trial would also randomize patients who may be at risk for a UTI to receive a probiotic&#xD;
      vs placebo. The primary outcome measurement will be the change in the ratio of Lactobacillus&#xD;
      to E. coli. As a secondary aim, the study will evaluate the incidence of UTI in the patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this study, the primary aim is to identify the change in the Lactobacillus E. coli ratio&#xD;
      within the lower urinary tract, the vagina, and the peri-rectal area in response to an oral&#xD;
      probiotic as well as to evaluate the stability of these changes following cessation of an&#xD;
      oral probiotic. Voided urine and peri-urethral, vaginal, and peri-rectal swab samples will be&#xD;
      analyzed for their Lactobacillus E. coli ratio using bacterial culture as well as 16S&#xD;
      ribosomal RNA gene sequencing. The study will compare the ratios present before, during, and&#xD;
      after oral probiotic usage. The study will also compare the change in ratios between subjects&#xD;
      taking the oral probiotic and those taking an oral placebo.&#xD;
&#xD;
      A secondary aim is to identify the normal daily changes (i.e. stability) in the bacterial&#xD;
      populations within the voided urine, including whether host intrinsic (e.g. diet, hygiene,&#xD;
      and sexual activity) and extrinsic (e.g. menstruation) factors affect the stability of&#xD;
      bacterial populations. The bacterial populations defining the voided urine samples will be&#xD;
      correlated to various daily subject-reported lifestyle variables. These include diet,&#xD;
      hygiene, sexual activity, medication usage, alcohol usage, menstruation, and urinary-related&#xD;
      symptoms. These lifestyle variables will be recorded each day for the entire duration of the&#xD;
      study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 1, 2017</start_date>
  <completion_date type="Actual">July 31, 2018</completion_date>
  <primary_completion_date type="Actual">July 31, 2018</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>
    <intervention_model_description>Participants are randomized to receive placebo or a probiotic using a 1:2 allocation, respectively</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>All participants and research team members are masked in this randomized placebo-controlled trial. The investigational pharmacist is unmasked.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Lactobacillus E. coli ratio in the rectum</measure>
    <time_frame>95 days</time_frame>
    <description>We will measure participants' rectal Lactobacillus E. coli ratio at baseline and after treatment. The change in this ratio will be recorded for each participant and compared between the placebo and intervention groups.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Lactobacillus E. coli ratio in the vagina</measure>
    <time_frame>95 days</time_frame>
    <description>We will measure participants' vaginal Lactobacillus E. coli ratio at baseline and after treatment. The change in this ratio will be recorded for each participant and compared between the placebo and intervention groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Lactobacillus E. coli ratio in the urethra</measure>
    <time_frame>95 days</time_frame>
    <description>We will measure participants' urethral Lactobacillus E. coli ratio at baseline and after treatment. The change in this ratio will be recorded for each participant and compared between the placebo and intervention groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevalence of urinary tract infections</measure>
    <time_frame>95 days</time_frame>
    <description>At the final study visit, we will record whether each participant experienced or did not experience a urinary tract infection (UTI). The odds of a UTI among those in the intervention cohort will be compared to the odds of a UTI in the placebo cohort.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants randomized to this group will take two placebo capsules daily during days 21-60.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intervention group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The intervention in this study is a probiotic. Participants randomized to this group will take two capsules of a probiotic daily during days 21-60</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Probiotic</intervention_name>
    <description>Participants randomized to the intervention group will receive Women's Fem Dophilus ® by Jarrow Formulas.</description>
    <arm_group_label>Intervention group</arm_group_label>
    <other_name>Fem Dophilus</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Participants randomized to the control group will receive a placebo containing no active ingredients</description>
    <arm_group_label>Control Group</arm_group_label>
    <other_name>Inactive substance</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pre-menopausal healthy women in the community (As defined by presence of menses at&#xD;
             least once in the last 12 months).&#xD;
&#xD;
          -  Age 18 years or older.&#xD;
&#xD;
          -  Agreement to collect daily samples (varying combinations of voided, periurethral, and&#xD;
             perianal swabs) for 3 months and bring the samples to Loyola University Medical Center&#xD;
&#xD;
          -  Agree to record and return a daily lifestyle diary&#xD;
&#xD;
          -  Understand and agree to taking daily oral probiotic or placebo while being blinded&#xD;
&#xD;
          -  Able to read and speak English&#xD;
&#xD;
          -  Able to obtain clean-catch urine&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Non-English speaking women&#xD;
&#xD;
          -  Allergy or contraindication to the probiotic used in this study&#xD;
&#xD;
          -  Prior participation in the study&#xD;
&#xD;
          -  Currently pregnant or lactating or planning a pregnancy within 6 months of consenting&#xD;
             to participate in the study&#xD;
&#xD;
          -  Inability to obtain a 'clean catch' urine sample&#xD;
&#xD;
          -  Subjects with an indwelling catheter&#xD;
&#xD;
          -  Males are excluded from participation&#xD;
&#xD;
          -  Women planning time away for more than 7 days following consent to participate in the&#xD;
             study&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Elizabeth Mueller, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Loyola University Health System</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Loyola University Medical Center</name>
      <address>
        <city>Maywood</city>
        <state>Illinois</state>
        <zip>60153</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Urinary Incontinence Treatment Network (UITN). The Trial of Mid-Urethral Slings (TOMUS): Design and Methodology. J Appl Res. 2008;8(1):AlboVol8No1.</citation>
    <PMID>24772006</PMID>
  </reference>
  <reference>
    <citation>FitzGerald MP, Brubaker L. Colpocleisis and urinary incontinence. Am J Obstet Gynecol. 2003 Nov;189(5):1241-4. doi: 10.1067/s0002-9378(03)00642-2.</citation>
    <PMID>14634547</PMID>
  </reference>
  <reference>
    <citation>Fitzgerald MP, Richter HE, Bradley CS, Ye W, Visco AC, Cundiff GW, Zyczynski HM, Fine P, Weber AM; Pelvic Floor Disorders Network. Pelvic support, pelvic symptoms, and patient satisfaction after colpocleisis. Int Urogynecol J Pelvic Floor Dysfunct. 2008 Dec;19(12):1603-9. doi: 10.1007/s00192-008-0696-6. Epub 2008 Aug 9.</citation>
    <PMID>18690402</PMID>
  </reference>
  <reference>
    <citation>Fok CS, McKinley K, Mueller ER, Kenton K, Schreckenberger P, Wolfe A, Brubaker L. Day of surgery urine cultures identify urogynecologic patients at increased risk for postoperative urinary tract infection. J Urol. 2013 May;189(5):1721-4. doi: 10.1016/j.juro.2012.11.167. Epub 2012 Dec 3.</citation>
    <PMID>23219547</PMID>
  </reference>
  <reference>
    <citation>Foxman B, Cronenwett AE, Spino C, Berger MB, Morgan DM. Cranberry juice capsules and urinary tract infection after surgery: results of a randomized trial. Am J Obstet Gynecol. 2015 Aug;213(2):194.e1-8. doi: 10.1016/j.ajog.2015.04.003. Epub 2015 Apr 13.</citation>
    <PMID>25882919</PMID>
  </reference>
  <reference>
    <citation>Beerepoot MA, ter Riet G, Verbon A, Nys S, de Reijke TM, Geerlings SE. [Non-antibiotic prophylaxis for recurrent urinary-tract infections]. Ned Tijdschr Geneeskd. 2006 Mar 11;150(10):541-4. Dutch.</citation>
    <PMID>16566416</PMID>
  </reference>
  <reference>
    <citation>Wilton L, Kollarova M, Heeley E, Shakir S. Relative risk of vaginal candidiasis after use of antibiotics compared with antidepressants in women: postmarketing surveillance data in England. Drug Saf. 2003;26(8):589-97. doi: 10.2165/00002018-200326080-00005.</citation>
    <PMID>12825971</PMID>
  </reference>
  <reference>
    <citation>Hooton TM. Recurrent urinary tract infection in women. Int J Antimicrob Agents. 2001 Apr;17(4):259-68. doi: 10.1016/s0924-8579(00)00350-2.</citation>
    <PMID>11295405</PMID>
  </reference>
  <reference>
    <citation>Raz R, Stamm WE. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. N Engl J Med. 1993 Sep 9;329(11):753-6. doi: 10.1056/NEJM199309093291102.</citation>
    <PMID>8350884</PMID>
  </reference>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>July 19, 2017</study_first_submitted>
  <study_first_submitted_qc>August 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <last_update_submitted>January 31, 2019</last_update_submitted>
  <last_update_submitted_qc>January 31, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 1, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Loyola University</investigator_affiliation>
    <investigator_full_name>Elizabeth Mueller</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Microbiome</keyword>
  <keyword>Lactobacillus</keyword>
  <keyword>Probiotic</keyword>
  <keyword>Fem-Dophilus</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>There is not a plan to make IPD available</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/NCT03250208
org study id: 209830
nct id: NCT03250208
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The study will enroll healthy pre-menopausal female volunteers in the community. These
      subjects will act as their own controls. The subjects will collect voided urine and
      peri-urethral swab specimens daily for several months. They will also be asked to collect
      vaginal and peri-rectal swab specimens at various time points. Subjects will document various
      lifestyle variables daily. During the middle of the study, subjects will be randomized to
      probiotic vs placebo. Using bacterial culture and 16S rRNA gene sequencing, the study will
      measure the bacterial populations of several anatomic sites longitudinally: voided urine,
      peri-urethra, vagina, and peri-rectal. The study hypothesizes that oral probiotic usage will
      alter the bacterial populations and ratio of Lactobacillus to E. coli within each of these
      sites. Additionally, the study hypothesizes that the changes within each site will occur
      first in the rectum (i.e. GI tract), followed by the vagina, and then the urethra and
      bladder.

      Using the prospective design of daily sampling and lifestyle variable documentation, the
      study may be able to identify possible influences on microbiome stability within the sampled
      sites. The lifestyle variables recorded include: diet, medication usage, menstruation, sexual
      activity, and alcohol consumption.

      This pilot study will establish the variance of the outcome variables among healthy women and
      confirm the emergence of the probiotic with the recommended dose. With this information,
      future researchers will be able to calculate the power needed for a larger randomized trial.
      This trial would also randomize patients who may be at risk for a UTI to receive a probiotic
      vs placebo. The primary outcome measurement will be the change in the ratio of Lactobacillus
      to E. coli. As a secondary aim, the study will evaluate the incidence of UTI in the patients.
In this study, the primary aim is to identify the change in the Lactobacillus E. coli ratio
      within the lower urinary tract, the vagina, and the peri-rectal area in response to an oral
      probiotic as well as to evaluate the stability of these changes following cessation of an
      oral probiotic. Voided urine and peri-urethral, vaginal, and peri-rectal swab samples will be
      analyzed for their Lactobacillus E. coli ratio using bacterial culture as well as 16S
      ribosomal RNA gene sequencing. The study will compare the ratios present before, during, and
      after oral probiotic usage. The study will also compare the change in ratios between subjects
      taking the oral probiotic and those taking an oral placebo.

      A secondary aim is to identify the normal daily changes (i.e. stability) in the bacterial
      populations within the voided urine, including whether host intrinsic (e.g. diet, hygiene,
      and sexual activity) and extrinsic (e.g. menstruation) factors affect the stability of
      bacterial populations. The bacterial populations defining the voided urine samples will be
      correlated to various daily subject-reported lifestyle variables. These include diet,
      hygiene, sexual activity, medication usage, alcohol usage, menstruation, and urinary-related
      symptoms. These lifestyle variables will be recorded each day for the entire duration of the
      study.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participants are randomized to receive placebo or a probiotic using a 1:2 allocation, respectively
primary purpose: Basic Science
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: All participants and research team members are masked in this randomized placebo-controlled trial. The investigational pharmacist is unmasked.
measure: Change in Lactobacillus E. coli ratio in the rectum
time frame: 95 days
description: We will measure participants' rectal Lactobacillus E. coli ratio at baseline and after treatment. The change in this ratio will be recorded for each participant and compared between the placebo and intervention groups.
measure: Change in Lactobacillus E. coli ratio in the vagina
time frame: 95 days
description: We will measure participants' vaginal Lactobacillus E. coli ratio at baseline and after treatment. The change in this ratio will be recorded for each participant and compared between the placebo and intervention groups.
measure: Change in Lactobacillus E. coli ratio in the urethra
time frame: 95 days
description: We will measure participants' urethral Lactobacillus E. coli ratio at baseline and after treatment. The change in this ratio will be recorded for each participant and compared between the placebo and intervention groups.
measure: Prevalence of urinary tract infections
time frame: 95 days
description: At the final study visit, we will record whether each participant experienced or did not experience a urinary tract infection (UTI). The odds of a UTI among those in the intervention cohort will be compared to the odds of a UTI in the placebo cohort.
arm group label: Control Group
arm group type: Placebo Comparator
description: Participants randomized to this group will take two placebo capsules daily during days 21-60.
arm group label: Intervention group
arm group type: Experimental
description: The intervention in this study is a probiotic. Participants randomized to this group will take two capsules of a probiotic daily during days 21-60
intervention type: Dietary Supplement
intervention name: Probiotic
description: Participants randomized to the intervention group will receive Women's Fem Dophilus ® by Jarrow Formulas.
arm group label: Intervention group
other name: Fem Dophilus
intervention type: Other
intervention name: Placebo
description: Participants randomized to the control group will receive a placebo containing no active ingredients
arm group label: Control Group
other name: Inactive substance
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Elizabeth Mueller, MD
role: Principal Investigator
affiliation: Loyola University Health System
facility: 
country: United States
citation: Urinary Incontinence Treatment Network (UITN). The Trial of Mid-Urethral Slings (TOMUS): Design and Methodology. J Appl Res. 2008;8(1):AlboVol8No1.
PMID: 24772006
citation: FitzGerald MP, Brubaker L. Colpocleisis and urinary incontinence. Am J Obstet Gynecol. 2003 Nov;189(5):1241-4. doi: 10.1067/s0002-9378(03)00642-2.
PMID: 14634547
citation: Fitzgerald MP, Richter HE, Bradley CS, Ye W, Visco AC, Cundiff GW, Zyczynski HM, Fine P, Weber AM; Pelvic Floor Disorders Network. Pelvic support, pelvic symptoms, and patient satisfaction after colpocleisis. Int Urogynecol J Pelvic Floor Dysfunct. 2008 Dec;19(12):1603-9. doi: 10.1007/s00192-008-0696-6. Epub 2008 Aug 9.
PMID: 18690402
citation: Fok CS, McKinley K, Mueller ER, Kenton K, Schreckenberger P, Wolfe A, Brubaker L. Day of surgery urine cultures identify urogynecologic patients at increased risk for postoperative urinary tract infection. J Urol. 2013 May;189(5):1721-4. doi: 10.1016/j.juro.2012.11.167. Epub 2012 Dec 3.
PMID: 23219547
citation: Foxman B, Cronenwett AE, Spino C, Berger MB, Morgan DM. Cranberry juice capsules and urinary tract infection after surgery: results of a randomized trial. Am J Obstet Gynecol. 2015 Aug;213(2):194.e1-8. doi: 10.1016/j.ajog.2015.04.003. Epub 2015 Apr 13.
PMID: 25882919
citation: Beerepoot MA, ter Riet G, Verbon A, Nys S, de Reijke TM, Geerlings SE. [Non-antibiotic prophylaxis for recurrent urinary-tract infections]. Ned Tijdschr Geneeskd. 2006 Mar 11;150(10):541-4. Dutch.
PMID: 16566416
citation: Wilton L, Kollarova M, Heeley E, Shakir S. Relative risk of vaginal candidiasis after use of antibiotics compared with antidepressants in women: postmarketing surveillance data in England. Drug Saf. 2003;26(8):589-97. doi: 10.2165/00002018-200326080-00005.
PMID: 12825971
citation: Hooton TM. Recurrent urinary tract infection in women. Int J Antimicrob Agents. 2001 Apr;17(4):259-68. doi: 10.1016/s0924-8579(00)00350-2.
PMID: 11295405
citation: Raz R, Stamm WE. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. N Engl J Med. 1993 Sep 9;329(11):753-6. doi: 10.1056/NEJM199309093291102.
PMID: 8350884
responsible party type: Principal Investigator
investigator affiliation: Loyola University
investigator full name: Elizabeth Mueller
investigator title: Associate Professor
sharing ipd: No
ipd description: There is not a plan to make IPD available