<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/NCT01680874</url>
  </required_header>
  <id_info>
    <org_study_id>2012-0462</org_study_id>
    <secondary_id>R03AG040669-01</secondary_id>
    <nct_id>NCT01680874</nct_id>
  </id_info>
  <brief_title>Probiotics for Clostridium Difficile Infection in Older Adults</brief_title>
  <acronym>PICO</acronym>
  <official_title>A Pilot Study to Examine the Role of Probiotics for Improving Outcomes of C. Difficile</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Wisconsin, Madison</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute on Aging (NIA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Wisconsin, Madison</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether a probiotic, when used together with&#xD;
      standard treatment, is effective in reducing duration of symptoms and preventing recurrence&#xD;
      of infection in older adults with a first episode of C. difficile infection.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Probiotics are live microorganisms that are available over the counter, widely used as&#xD;
      dietary supplements or nutritional foods, and represent a low-cost, well tolerated, safe,&#xD;
      non-antibiotic based strategy that may have efficacy as adjunctive treatment of infections&#xD;
      without the attendant risks of promoting antimicrobial resistance. Certain probiotics have&#xD;
      demonstrated inhibition of adherence of pathogenic bacteria and stimulation of systemic&#xD;
      immune functions, possibly enhancing the body's ability to eradicate C. difficile in the&#xD;
      gastrointestinal tract. However, limited data is available on the efficacy of probiotics for&#xD;
      ameliorating C. difficile symptoms and reducing recurrence of C. difficile infection (CDI).&#xD;
      The investigators propose a pilot randomized, double-blind, placebo-controlled clinical trial&#xD;
      in older adult inpatients with a first episode of CDI to evaluate the efficacy of a probiotic&#xD;
      combination, in conjunction with standard treatment, for reducing duration of diarrhea and&#xD;
      recurrence of CDI.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2013</start_date>
  <completion_date type="Actual">February 2015</completion_date>
  <primary_completion_date type="Actual">February 2015</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>Duration of diarrhea</measure>
    <time_frame>4 weeks</time_frame>
    <description>Duration of diarrhea, as indicated by a stool diary kept by the patient</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Density of C. difficile toxin in stool</measure>
    <time_frame>8 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stool cytokines</measure>
    <time_frame>8 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fecal lactoferrin</measure>
    <time_frame>8 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional assessment using Barthel Index</measure>
    <time_frame>8 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recurrence of CDI</measure>
    <time_frame>8 weeks</time_frame>
    <description>Diagnosis with a recurrent episode of C. difficile infection</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Infection with Lactobacillus</measure>
    <time_frame>8 weeks</time_frame>
    <description>Fever and other signs of infection with Lactobacillus, and infection confirmed through blood cultures</description>
  </other_outcome>
  <other_outcome>
    <measure>Infection with Bifidobacterium</measure>
    <time_frame>8 weeks</time_frame>
    <description>Fever and other signs of infection with Bifidobacterium, and infection confirmed through blood cultures</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">33</enrollment>
  <condition>Clostridium Difficile</condition>
  <arm_group>
    <arm_group_label>Probiotic</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This arm will receive a probiotic combination which will consist of equal amounts of Lactobacillus acidophilus NCFM® (ATCC 700396), Lactobacillus paracasei Lpc-37 (ATCC SD5275), Bifidobacterium lactis Bi-07 (ATCC SC5220), and Bifidobacterium lactis Bl-04 (ATCC SD5219).&#xD;
The probiotic will be taken orally, once a week, for 4 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>A placebo will be taken orally, once a day, for 4 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Probiotic</intervention_name>
    <description>The intervention will consist of the subject taking the study medication once a day for 4 weeks. During hospitalization, patients will be followed daily for diarrhea history, record of concomitant medications, adverse effects (AEs), and their response to treatment using a stool diary. Upon discharge from the hospital, patients will be contacted through weekly phone calls to assess diarrhea history, record of concomitant medications, adverse effects (AEs), and their response to treatment using a stool diary. At weeks 4 and 8, a stool sample will be collected, and the stool diary will be reviewed.</description>
    <arm_group_label>Probiotic</arm_group_label>
    <other_name>Lactobacillus acidophilus NCFM®</other_name>
    <other_name>Lactobacillus paracasei Lpc-37</other_name>
    <other_name>Bifidobacterium lactis Bi-07</other_name>
    <other_name>Bifidobacterium lactis Bl-04</other_name>
    <other_name>ATCC 700396</other_name>
    <other_name>ATCC SD5275</other_name>
    <other_name>ATCC SD5220</other_name>
    <other_name>ATCC SD5219</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>The intervention will consist of the subject taking the placebo once a day for 4 weeks. day for 4 weeks. During hospitalization, patients will be followed daily for diarrhea history, record of concomitant medications, adverse effects (AEs), and their response to treatment using a stool diary. Upon discharge from the hospital, patients will be contacted through weekly phone calls to assess diarrhea history, record of concomitant medications, adverse effects (AEs), and their response to treatment using a stool diary. At weeks 4 and 8, a stool sample will be collected, and the stool diary will be reviewed.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult of either gender, 18 years or older with a first episode of C. difficile&#xD;
             infection&#xD;
&#xD;
          -  Meets the case definition of C. difficile infection-diarrhea associated with a&#xD;
             positive stool test for C. difficile toxin(s) in the 2 days prior to enrollment&#xD;
             treated with metronidazole or vancomycin&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe disease defined as any of the following: WBC &gt; 30,000 or &lt; 1000 cells/mm^3,&#xD;
             elevated creatinine &gt; 1.5 times the premorbid level, ICU patient at time C. difficile&#xD;
             infection diagnosed&#xD;
&#xD;
          -  Has other known etiology of diarrhea (e.g. other enteric pathogen, other intestinal&#xD;
             disease)&#xD;
&#xD;
          -  Has a history of chronic intestinal disease (e.g. Crohn's disease, ulcerative colitis)&#xD;
&#xD;
          -  Has a presence of toxic megacolon or ileus&#xD;
&#xD;
          -  Has a presence of colostomy or nasogastric tube&#xD;
&#xD;
          -  Has a history of abdominal surgery within the previous 3 months (from time of&#xD;
             enrollment)&#xD;
&#xD;
          -  Is enrolled in another investigational drug trial&#xD;
&#xD;
          -  Is unavailable for follow-up visits&#xD;
&#xD;
          -  History of multiple C. difficile infection&#xD;
&#xD;
          -  Willing not to take other probiotics for duration of study&#xD;
&#xD;
          -  Is severely immunocompromised.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nasia Safdar, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Wisconsin Department of Medicine (Infectious Disease)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Wisconsin Hospital and Clinics</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Alvarez-Olmos MI, Oberhelman RA. Probiotic agents and infectious diseases: a modern perspective on a traditional therapy. Clin Infect Dis. 2001 Jun 1;32(11):1567-76. doi: 10.1086/320518. Epub 2001 May 4.</citation>
    <PMID>11340528</PMID>
  </reference>
  <reference>
    <citation>McFarland LV. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol. 2006 Apr;101(4):812-22. doi: 10.1111/j.1572-0241.2006.00465.x.</citation>
    <PMID>16635227</PMID>
  </reference>
  <reference>
    <citation>Safdar N, Barigala R, Said A, McKinley L. Feasibility and tolerability of probiotics for prevention of antibiotic-associated diarrhoea in hospitalized US military veterans. J Clin Pharm Ther. 2008 Dec;33(6):663-8. doi: 10.1111/j.1365-2710.2008.00980.x.</citation>
    <PMID>19138244</PMID>
  </reference>
  <verification_date>December 2015</verification_date>
  <study_first_submitted>September 4, 2012</study_first_submitted>
  <study_first_submitted_qc>September 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 7, 2012</study_first_posted>
  <last_update_submitted>December 1, 2015</last_update_submitted>
  <last_update_submitted_qc>December 1, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 3, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Clostridium difficile</keyword>
  <keyword>Diarrhea</keyword>
  <keyword>Infection</keyword>
  <keyword>Lactobacilli</keyword>
  <keyword>Bifidobacteria</keyword>
  <keyword>Lactobacillus acidophilus</keyword>
  <keyword>Lactobacillus paracasei</keyword>
  <keyword>Bifidobacterium lactis</keyword>
  <keyword>Yogurt</keyword>
  <keyword>Probiotics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Clostridium Infections</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/NCT01680874
org study id: 2012-0462
secondary id: R03AG040669-01
nct id: NCT01680874
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
The purpose of this study is to determine whether a probiotic, when used together with
      standard treatment, is effective in reducing duration of symptoms and preventing recurrence
      of infection in older adults with a first episode of C. difficile infection.
Probiotics are live microorganisms that are available over the counter, widely used as
      dietary supplements or nutritional foods, and represent a low-cost, well tolerated, safe,
      non-antibiotic based strategy that may have efficacy as adjunctive treatment of infections
      without the attendant risks of promoting antimicrobial resistance. Certain probiotics have
      demonstrated inhibition of adherence of pathogenic bacteria and stimulation of systemic
      immune functions, possibly enhancing the body's ability to eradicate C. difficile in the
      gastrointestinal tract. However, limited data is available on the efficacy of probiotics for
      ameliorating C. difficile symptoms and reducing recurrence of C. difficile infection (CDI).
      The investigators propose a pilot randomized, double-blind, placebo-controlled clinical trial
      in older adult inpatients with a first episode of CDI to evaluate the efficacy of a probiotic
      combination, in conjunction with standard treatment, for reducing duration of diarrhea and
      recurrence of CDI.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Duration of diarrhea
time frame: 4 weeks
description: Duration of diarrhea, as indicated by a stool diary kept by the patient
measure: Density of C. difficile toxin in stool
time frame: 8 weeks
measure: Stool cytokines
time frame: 8 weeks
measure: Fecal lactoferrin
time frame: 8 weeks
measure: Functional assessment using Barthel Index
time frame: 8 weeks
measure: Recurrence of CDI
time frame: 8 weeks
description: Diagnosis with a recurrent episode of C. difficile infection
measure: Infection with Lactobacillus
time frame: 8 weeks
description: Fever and other signs of infection with Lactobacillus, and infection confirmed through blood cultures
measure: Infection with Bifidobacterium
time frame: 8 weeks
description: Fever and other signs of infection with Bifidobacterium, and infection confirmed through blood cultures
arm group label: Probiotic
arm group type: Experimental
description: This arm will receive a probiotic combination which will consist of equal amounts of Lactobacillus acidophilus NCFM® (ATCC 700396), Lactobacillus paracasei Lpc-37 (ATCC SD5275), Bifidobacterium lactis Bi-07 (ATCC SC5220), and Bifidobacterium lactis Bl-04 (ATCC SD5219).
The probiotic will be taken orally, once a week, for 4 weeks.
arm group label: Placebo
arm group type: Placebo Comparator
description: A placebo will be taken orally, once a day, for 4 weeks.
intervention type: Dietary Supplement
intervention name: Probiotic
description: The intervention will consist of the subject taking the study medication once a day for 4 weeks. During hospitalization, patients will be followed daily for diarrhea history, record of concomitant medications, adverse effects (AEs), and their response to treatment using a stool diary. Upon discharge from the hospital, patients will be contacted through weekly phone calls to assess diarrhea history, record of concomitant medications, adverse effects (AEs), and their response to treatment using a stool diary. At weeks 4 and 8, a stool sample will be collected, and the stool diary will be reviewed.
arm group label: Probiotic
other name: Lactobacillus acidophilus NCFM®
other name: Lactobacillus paracasei Lpc-37
other name: Bifidobacterium lactis Bi-07
other name: Bifidobacterium lactis Bl-04
other name: ATCC 700396
other name: ATCC SD5275
other name: ATCC SD5220
other name: ATCC SD5219
intervention type: Dietary Supplement
intervention name: Placebo
description: The intervention will consist of the subject taking the placebo once a day for 4 weeks. day for 4 weeks. During hospitalization, patients will be followed daily for diarrhea history, record of concomitant medications, adverse effects (AEs), and their response to treatment using a stool diary. Upon discharge from the hospital, patients will be contacted through weekly phone calls to assess diarrhea history, record of concomitant medications, adverse effects (AEs), and their response to treatment using a stool diary. At weeks 4 and 8, a stool sample will be collected, and the stool diary will be reviewed.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Nasia Safdar, MD
role: Principal Investigator
affiliation: University of Wisconsin Department of Medicine (Infectious Disease)
facility: 
country: United States
citation: Alvarez-Olmos MI, Oberhelman RA. Probiotic agents and infectious diseases: a modern perspective on a traditional therapy. Clin Infect Dis. 2001 Jun 1;32(11):1567-76. doi: 10.1086/320518. Epub 2001 May 4.
PMID: 11340528
citation: McFarland LV. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol. 2006 Apr;101(4):812-22. doi: 10.1111/j.1572-0241.2006.00465.x.
PMID: 16635227
citation: Safdar N, Barigala R, Said A, McKinley L. Feasibility and tolerability of probiotics for prevention of antibiotic-associated diarrhoea in hospitalized US military veterans. J Clin Pharm Ther. 2008 Dec;33(6):663-8. doi: 10.1111/j.1365-2710.2008.00980.x.
PMID: 19138244
responsible party type: Sponsor
mesh term: Clostridium Infections