<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/NCT03778606</url>
  </required_header>
  <id_info>
    <org_study_id>PRO00033794</org_study_id>
    <nct_id>NCT03778606</nct_id>
  </id_info>
  <brief_title>Oligosaccharide for Cdiff(+) Heme-onc Patients</brief_title>
  <official_title>Oligosaccharide Supplementation Among Hematology-Oncology Clostridium Difficile Colonized Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical College of Wisconsin</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical College of Wisconsin</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>
      Clostridium difficile causes ~453,000 infections and ~29,300 deaths per year in the US,&#xD;
      making it the most common hospital acquired infection in the country. C. difficile is an&#xD;
      anaerobic bacterium that has the capacity to inhabit the colon of humans and other mammals.&#xD;
      Initially thought to be a commensal, it was later found to be associated with antibiotic&#xD;
      induced enterocolitis. Since then, it has gradually become one of the most important&#xD;
      healthcare associated pathogens. C. difficile infection (CDI) causes colitis, which is&#xD;
      inflammation of the colonic mucosa with a spectrum of severity from mild to more protracted&#xD;
      diarrhea, abdominal pain, fever, toxic megacolon, sepsis, and in some instances death.&#xD;
      Mortality occurs despite the existence of three antibiotic options. CDI is also associated&#xD;
      with higher hospital readmission rates, and associated healthcare costs in the US are&#xD;
      estimated at 4.8 billion dollars annually. Due to the significance of C. difficile in&#xD;
      healthcare, hospital level C. difficile rates are publically reported and closely scrutinized&#xD;
      by the Centers for Medicare and Medicaid. Standard infection control bundles are proving to&#xD;
      be insufficient for controlling the national C. difficile problem. Better understanding of&#xD;
      the biological steps preceding clinical infection and reversal of the underlying gut&#xD;
      dysbiosis will allow us to curtail our C. difficile epidemic. The present study aims to&#xD;
      manipulate the gut microbiota to halt the biological progression of C. difficile.&#xD;
&#xD;
      CDI is a serious problem in hematology-oncology patients. The incidence of CDI in the&#xD;
      hematology-oncology population is much higher than in other populations and&#xD;
      hematology-oncology inpatient units frequently have the highest incidence of CDI cases within&#xD;
      an institution. Additionally, hematology-oncology patients have high rates of C. difficile&#xD;
      colonization upon hospitalization and more than 50% of patients detected with C. difficile&#xD;
      colonization before bone marrow transplantation end up diagnosed with hospital associated&#xD;
      CDI. This finding is not trivial as CDI treatment with oral vancomycin causes major and&#xD;
      prolonged perturbations of their intestinal microbiota, which has been associated with higher&#xD;
      mortality. In addition to the usual complications of CDI, a higher incidence of&#xD;
      graft-versus-host-disease has been described in patients with CDI.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Aim 1/Objective 1. Establish the feasibility of oligosaccharide supplementation and twice a&#xD;
      week stool collections among 12 C. difficile colonized hematology-oncology inpatients. It&#xD;
      will be determined if at least 70% of the oligosaccharide dosages are taken by at least 8&#xD;
      (&gt;=66%) of the 12 enrolled patients. Additionally, the ability to collect at least 50% of the&#xD;
      scheduled stool samples will be evaluated.&#xD;
&#xD;
      Aim 1 will provide important information about the ideal food/drink to mix the potato starch&#xD;
      supplemented in this study. The knowledge gained in this pilot will be used to design a&#xD;
      future phase II or III clinical trial.&#xD;
&#xD;
      Aim 2. Explore the impact of oligosaccharide supplementation on C. difficile loads and&#xD;
      relative abundance of Firmicutes. All stool samples will undergo 16S ribosomal ribonucleic&#xD;
      acid (rRNA) and bioinformatics at the MCW's Genomic and Precision Medicine Center and C.&#xD;
      difficile quantitative polymerase chain reaction (qPCR) at the PI's research laboratory.&#xD;
      Historical controls will be obtained from a group of over 450 hematology-oncology inpatients&#xD;
      who underwent at least one C. difficile surveillance test and whose stool samples are&#xD;
      currently being processed for 16S rRNA by the PI's team. Controls at a 3:1 ratio with cases&#xD;
      will be matched based on underlying disease, unit of admission, antibiotic use, baseline C.&#xD;
      difficile fecal loads, and baseline relative abundance of Firmicutes.&#xD;
&#xD;
      Objective 2a. Evaluate the impact of oligosaccharide supplementation on the change of C.&#xD;
      difficile fecal loads when compared to historical controls.&#xD;
&#xD;
      Objective 2b. Explore the effect of oligosaccharide supplementation on the change in relative&#xD;
      abundance of Firmicutes when compared to historical controls.&#xD;
&#xD;
      It is expected a reduction will occur in C. difficile fecal loads during oligosaccharide&#xD;
      supplementation when compared to matched controls. Conversely, it is expected an increase in&#xD;
      the relative abundance of Firmicutes (or some of its operational taxonomic units; OTUs)&#xD;
      during oligosaccharide replacement will occur when compared to matched controls. The&#xD;
      knowledge gained with Objectives 2a and 2b will be used to determine the sample size needed&#xD;
      to design future phase II or phase III clinical trials.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2019</start_date>
  <completion_date type="Actual">August 1, 2021</completion_date>
  <primary_completion_date type="Actual">July 31, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Stool samples will be collected twice a week while on potato starch supplementation and 1 time at 7-days post- starch supplementation to assess any changes in the frequency of collection during the 21-day period.</measure>
    <time_frame>Day 1- Day 21</time_frame>
    <description>Samples will be collected twice a week (4-5 times during supplementation) and one time at day 21 or discharge, whichever happens first.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Oligosaccharide intake assessed by a patient diary to measure supplementation feasibility</measure>
    <time_frame>Day 1-Day 14</time_frame>
    <description>Patients will be provided with a diary in which they will document compliance with oligosaccharide intake. It is anticipated ≥70% of intended doses to be fully administered by the patient.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The feasibility of collecting all available stool samples stool will be assessed. A rate ≥50% of correctly collected and processed samples will be considered feasible.</measure>
    <time_frame>Day 1-Day 14</time_frame>
    <description>It is expected ≥50% of stool samples to be correctly collected and processed.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in C. difficile loads will be assessed using C. difficile quantitative polymerase chain reaction (qPCR).</measure>
    <time_frame>Day 1-Day 14</time_frame>
    <description>Stool samples collected for diagnosis and any additional stool collections will be thawed in batches and one cc aliquot will be extracted refreezing the remaining sample at -80 degrees F. One cc aliquot will then be divided into 4 sub-samples of equal volume and with the same unique identifier. This identifier will be able to chronologically cluster samples by each unique patient. A sample will be used for C. difficile qPCR quantitative determination.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Firmicutes' relative abundance due to oligosaccharide supplementation measured by 16S rRNA gene sequencing</measure>
    <time_frame>Day 1-Day 14</time_frame>
    <description>Sub-sample of stool from diagnosis, and additional stool collections will be used for 16S ribosomal ribonucleic acid gene sequencing to determine the microbiome community structure</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Clostridium Difficile</condition>
  <condition>Hematologic Diseases</condition>
  <arm_group>
    <arm_group_label>Potato starch supplementation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Twelve patients found to be colonized with C. difficile will undergo twice a day potato starch supplementation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Potato starch</intervention_name>
    <description>Potato starch will be given twice a day for up to 14 days, discharge, or death, whichever occurs first.</description>
    <arm_group_label>Potato starch supplementation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients must meet all inclusion criteria to be eligible to participate in the study.&#xD;
&#xD;
          -  Patients must be at least 18 years of age at time of consent.&#xD;
&#xD;
          -  Positive C. difficile surveillance test.&#xD;
&#xD;
          -  Absence of diarrhea or abdominal pain within the past 48 hours.&#xD;
&#xD;
          -  Patient admitted in a hematology-oncology unit which for the purposes of this study&#xD;
             will be defined as 7-CFAC and 8-CFAC.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients must NOT meet any exclusion criteria to be eligible to participate in the study.&#xD;
&#xD;
          -  Presence of &gt;= grade I nausea/vomiting.&#xD;
&#xD;
          -  Inability to take oral medications or food.&#xD;
&#xD;
          -  Expected length of hospitalization or survival less than 5 days&#xD;
&#xD;
          -  Patient is only boarding in hematology-oncology units and would have not otherwise&#xD;
             been admitted to these units.&#xD;
&#xD;
          -  Unwillingness or inability to provide written informed consent.&#xD;
&#xD;
          -  Women known to be pregnant or lactating during the study.&#xD;
&#xD;
          -  History of inflammatory bowel disease.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Medical College of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>November 30, 2018</study_first_submitted>
  <study_first_submitted_qc>December 14, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>October 12, 2021</last_update_submitted>
  <last_update_submitted_qc>October 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 13, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical College of Wisconsin</investigator_affiliation>
    <investigator_full_name>Silvia Munoz-Price</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Clostridium difficile</keyword>
  <keyword>Asymptomatic carrier</keyword>
  <keyword>Potato starch</keyword>
  <keyword>Non digestable oligosaccharide</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Clostridium Infections</mesh_term>
    <mesh_term>Hematologic Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </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/NCT03778606
org study id: PRO00033794
nct id: NCT03778606
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Clostridium difficile causes ~453,000 infections and ~29,300 deaths per year in the US,
      making it the most common hospital acquired infection in the country. C. difficile is an
      anaerobic bacterium that has the capacity to inhabit the colon of humans and other mammals.
      Initially thought to be a commensal, it was later found to be associated with antibiotic
      induced enterocolitis. Since then, it has gradually become one of the most important
      healthcare associated pathogens. C. difficile infection (CDI) causes colitis, which is
      inflammation of the colonic mucosa with a spectrum of severity from mild to more protracted
      diarrhea, abdominal pain, fever, toxic megacolon, sepsis, and in some instances death.
      Mortality occurs despite the existence of three antibiotic options. CDI is also associated
      with higher hospital readmission rates, and associated healthcare costs in the US are
      estimated at 4.8 billion dollars annually. Due to the significance of C. difficile in
      healthcare, hospital level C. difficile rates are publically reported and closely scrutinized
      by the Centers for Medicare and Medicaid. Standard infection control bundles are proving to
      be insufficient for controlling the national C. difficile problem. Better understanding of
      the biological steps preceding clinical infection and reversal of the underlying gut
      dysbiosis will allow us to curtail our C. difficile epidemic. The present study aims to
      manipulate the gut microbiota to halt the biological progression of C. difficile.

      CDI is a serious problem in hematology-oncology patients. The incidence of CDI in the
      hematology-oncology population is much higher than in other populations and
      hematology-oncology inpatient units frequently have the highest incidence of CDI cases within
      an institution. Additionally, hematology-oncology patients have high rates of C. difficile
      colonization upon hospitalization and more than 50% of patients detected with C. difficile
      colonization before bone marrow transplantation end up diagnosed with hospital associated
      CDI. This finding is not trivial as CDI treatment with oral vancomycin causes major and
      prolonged perturbations of their intestinal microbiota, which has been associated with higher
      mortality. In addition to the usual complications of CDI, a higher incidence of
      graft-versus-host-disease has been described in patients with CDI.
Aim 1/Objective 1. Establish the feasibility of oligosaccharide supplementation and twice a
      week stool collections among 12 C. difficile colonized hematology-oncology inpatients. It
      will be determined if at least 70% of the oligosaccharide dosages are taken by at least 8
      (>=66%) of the 12 enrolled patients. Additionally, the ability to collect at least 50% of the
      scheduled stool samples will be evaluated.

      Aim 1 will provide important information about the ideal food/drink to mix the potato starch
      supplemented in this study. The knowledge gained in this pilot will be used to design a
      future phase II or III clinical trial.

      Aim 2. Explore the impact of oligosaccharide supplementation on C. difficile loads and
      relative abundance of Firmicutes. All stool samples will undergo 16S ribosomal ribonucleic
      acid (rRNA) and bioinformatics at the MCW's Genomic and Precision Medicine Center and C.
      difficile quantitative polymerase chain reaction (qPCR) at the PI's research laboratory.
      Historical controls will be obtained from a group of over 450 hematology-oncology inpatients
      who underwent at least one C. difficile surveillance test and whose stool samples are
      currently being processed for 16S rRNA by the PI's team. Controls at a 3:1 ratio with cases
      will be matched based on underlying disease, unit of admission, antibiotic use, baseline C.
      difficile fecal loads, and baseline relative abundance of Firmicutes.

      Objective 2a. Evaluate the impact of oligosaccharide supplementation on the change of C.
      difficile fecal loads when compared to historical controls.

      Objective 2b. Explore the effect of oligosaccharide supplementation on the change in relative
      abundance of Firmicutes when compared to historical controls.

      It is expected a reduction will occur in C. difficile fecal loads during oligosaccharide
      supplementation when compared to matched controls. Conversely, it is expected an increase in
      the relative abundance of Firmicutes (or some of its operational taxonomic units; OTUs)
      during oligosaccharide replacement will occur when compared to matched controls. The
      knowledge gained with Objectives 2a and 2b will be used to determine the sample size needed
      to design future phase II or phase III clinical trials.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Stool samples will be collected twice a week while on potato starch supplementation and 1 time at 7-days post- starch supplementation to assess any changes in the frequency of collection during the 21-day period.
time frame: Day 1- Day 21
description: Samples will be collected twice a week (4-5 times during supplementation) and one time at day 21 or discharge, whichever happens first.
measure: Oligosaccharide intake assessed by a patient diary to measure supplementation feasibility
time frame: Day 1-Day 14
description: Patients will be provided with a diary in which they will document compliance with oligosaccharide intake. It is anticipated ≥70% of intended doses to be fully administered by the patient.
measure: The feasibility of collecting all available stool samples stool will be assessed. A rate ≥50% of correctly collected and processed samples will be considered feasible.
time frame: Day 1-Day 14
description: It is expected ≥50% of stool samples to be correctly collected and processed.
measure: Changes in C. difficile loads will be assessed using C. difficile quantitative polymerase chain reaction (qPCR).
time frame: Day 1-Day 14
description: Stool samples collected for diagnosis and any additional stool collections will be thawed in batches and one cc aliquot will be extracted refreezing the remaining sample at -80 degrees F. One cc aliquot will then be divided into 4 sub-samples of equal volume and with the same unique identifier. This identifier will be able to chronologically cluster samples by each unique patient. A sample will be used for C. difficile qPCR quantitative determination.
measure: Changes in Firmicutes' relative abundance due to oligosaccharide supplementation measured by 16S rRNA gene sequencing
time frame: Day 1-Day 14
description: Sub-sample of stool from diagnosis, and additional stool collections will be used for 16S ribosomal ribonucleic acid gene sequencing to determine the microbiome community structure
arm group label: Potato starch supplementation
arm group type: Experimental
description: Twelve patients found to be colonized with C. difficile will undergo twice a day potato starch supplementation.
intervention type: Dietary Supplement
intervention name: Potato starch
description: Potato starch will be given twice a day for up to 14 days, discharge, or death, whichever occurs first.
arm group label: Potato starch supplementation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Medical College of Wisconsin
investigator full name: Silvia Munoz-Price
investigator title: Professor
mesh term: Clostridium Infections
mesh term: Hematologic Diseases
sharing ipd: Undecided