<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/NCT03268213</url>
  </required_header>
  <id_info>
    <org_study_id>479696</org_study_id>
    <nct_id>NCT03268213</nct_id>
  </id_info>
  <brief_title>Fecal Microbial Transplantation for C. Difficile and/or Ulcerative Colitis or Indeterminate Colitis</brief_title>
  <acronym>FMT</acronym>
  <official_title>Fecal Microbial Transplantation in Patients With Medication Refractory Clostridium Difficile and/or Ulcerative Colitis or Indeterminate Colitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stony Brook University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Stony Brook University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Fecal Microbiota Transplantation will be offered to eligible C. difficile patients (does not&#xD;
      require Investigational New Drug designation) and to eligible ulcerative colitis or&#xD;
      indeterminate colitis patients as Investigational New Drug treatment&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The following hypothesis will be tested in this study:&#xD;
&#xD;
        1. Fecal microbiota transplantation is a safe, tolerable, and efficacious procedure for C.&#xD;
           difficile patients and is a safe and tolerable procedure for ulcerative colitis and&#xD;
           indeterminate colitis patients.&#xD;
&#xD;
        2. The fecal microbial diversity, composition and function in stool recipients after fecal&#xD;
           transplantation will change to a similar microbial diversity, composition and&#xD;
           functionality as found in donor stool.&#xD;
&#xD;
      Primary objectives:&#xD;
&#xD;
      1. To determine the short term safety and tolerability of fecal microbiota transplantation in&#xD;
      patients with recurrent or refractory Clostridium difficile and medication refractory&#xD;
      Ulcerative colitis or indeterminate colitis up to 12 weeks post-transplant.&#xD;
&#xD;
      Secondary objectives:&#xD;
&#xD;
      1a. To determine the long term safety and tolerability of fecal microbiota transplantation up&#xD;
      to 1 year post-transplant in patients with recurrent or refractory Clostridium difficile and&#xD;
      medication refractory Ulcerative colitis or indeterminate colitis.&#xD;
&#xD;
      1b. To determine the efficacy of fecal microbiota transplantation in patients with recurrent&#xD;
      or refractory Clostridium difficile defined as no recurrence of C. difficile within one year.&#xD;
&#xD;
      2. To compare microbial diversity in healthy donor stools compared to pre-FMT recipient&#xD;
      stools collected from patients (recipients) with recurrent or refractory Clostridium&#xD;
      difficile and medication refractory Ulcerative colitis or indeterminate colitis.&#xD;
&#xD;
      3. To compare microbial composition in healthy donor stools compared to pre-FMT recipient&#xD;
      stools from patients (recipients) with recurrent or refractory Clostridium difficile and&#xD;
      medication refractory Ulcerative colitis or indeterminate colitis.&#xD;
&#xD;
      4. To compare microbial function in healthy donor stools compared to pre-FMT recipient stools&#xD;
      from patients (recipients) with recurrent or refractory Clostridium difficile and medication&#xD;
      refractory Ulcerative colitis or indeterminate colitis.&#xD;
&#xD;
      5. To compare microbial diversity in healthy donor stools and pre-FMT recipient stools with 1&#xD;
      week post-transplant recipient stool samples collected from patients (recipients) with&#xD;
      recurrent or refractory Clostridium difficile and medication refractory Ulcerative colitis or&#xD;
      indeterminate colitis.&#xD;
&#xD;
      6. To compare microbial composition in healthy donor stools and pre-FMT recipient stools with&#xD;
      1 week post-transplant recipient stool samples collected from patients (recipients) with&#xD;
      recurrent or refractory Clostridium difficile and medication refractory Ulcerative colitis or&#xD;
      indeterminate colitis.&#xD;
&#xD;
      7. To compare microbial function in healthy donor stools and pre-FMT recipient stools with 1&#xD;
      week post-transplant recipient stool samples collected from patients (recipients) with&#xD;
      recurrent or refractory Clostridium difficile and medication refractory Ulcerative colitis or&#xD;
      indeterminate colitis.&#xD;
&#xD;
      8. To compare microbial diversity in healthy donor stools and pre-FMT recipient stools with&#xD;
      12 week post transplant recipient stool samples collected from patients (recipients) with&#xD;
      recurrent or refractory Clostridium difficile and medication refractory Ulcerative colitis or&#xD;
      indeterminate colitis.&#xD;
&#xD;
      9. To compare microbial composition in healthy donor stools and pre-FMT recipient stools with&#xD;
      12 week post transplant recipient stool samples collected from patients (recipients) with&#xD;
      recurrent or refractory Clostridium difficile and medication refractory Ulcerative colitis or&#xD;
      indeterminate colitis.&#xD;
&#xD;
      10. To compare microbial function in healthy donor stools and pre-FMT recipient stools with&#xD;
      12 week post transplant recipient stool samples collected from patients (recipients) with&#xD;
      recurrent or refractory Clostridium difficile and medication refractory Ulcerative colitis or&#xD;
      indeterminate colitis.&#xD;
&#xD;
      11. Stool calprotectin levels will be measured in the recipient at baseline pre-FMT, 1 week&#xD;
      and 12 weeks post FMT to determine if FMT causes a statistically significant change.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2013</start_date>
  <completion_date type="Actual">February 15, 2022</completion_date>
  <primary_completion_date type="Actual">February 15, 2022</primary_completion_date>
  <phase>Early Phase 1</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>
    <intervention_model_description>FMT is offered as a treatment to eligible patients</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>9 years</time_frame>
    <description>Number of participants with treatment-related adverse events with grade greater than 2 within one year after FMT will be reported.&#xD;
Safety will be assessed as a report of no new medical condition after the transplant, Tolerability, as recorded by report of no serious adverse events after the transplant and Efficacy of the procedure will be recorded as improvement in clinical symptoms during any clinically indicated colonoscopies after the transplant as compared to before transplant&#xD;
C. Diff patients will have a negative C. diff test report after the transplant as an out come measure.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To measure the effect of fecal microbial transplantation on microbial diversity in healthy donor stools compared to pre-FMT, 1 week post FMT, and 12 weeks post-FMT recipient stools.</measure>
    <time_frame>10 years</time_frame>
    <description>Fecal DNA samples will undergo V3-V4 16S rRNA sequencing. Operational taxonomic units (OTUs) will be produced by clustering sequences with identical taxonomic assignments. Alpha diversity indices (e.g. Chao1, Shannon complexity H, Shannon Evenness H/Hmax) will be calculated inferred through 1000 replicate resamplings using Explicet. Beta diversity (Bray-Curtis and Jaccard distances) will be calculated for the recipient Pre-FMT, 1 week post-FMT and 12 weeks post-FMT as compared to their pared donor using the adonis function in the R vegan package at the phyla, family and genus level. A linear mixed model will be used to compare alpha-diversity (ShannonH) and beta-diversity (Bray-Curtis and Jaccard distance) between each timepoint (FMT) and each disease group (Group). P-values less than 0.05 were considered as statistically significant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To measure the effect of fecal microbial transplantation on microbial composition in healthy donor stools compared to pre-FMT, 1 week post FMT, and 12 weeks post-FMT recipient stools.</measure>
    <time_frame>10 years</time_frame>
    <description>Fecal DNA samples will undergo V3-V4 16S rRNA sequencing. Operational taxonomic units (OTUs) will be produced by clustering sequences with identical taxonomic assignments. Linear mixed models analyses on individual OTUs at the genus level will be conducted on 105 OTUs after eliminating OTUs with an average relative abundance of &lt; 0.001% in the donor and recipient pre-FMT samples, and after discarding OTUs where more than 75% of the samples had a zero count. To compare the relative abundance of each OTU between timepoints before and after FMT [pre-transplant recipient, 1-wk. post-FMT recipient, 3-mos. post-FMT recipient] and each disease group, a generalized linear mixed model (GLMM) or generalized estimating equation (GEE) will be used by taking the actual counts of each OTU as the outcomes that were assumed to follow a negative binomial distribution. The p-values will be adjusted for multiple comparisons by the Bonferroni correction or by the Benjamin-Hochberg method (FDR &lt; 0.05).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To measure the effect of fecal microbial transplantation on microbial function using shotgun DNA metagenomic in healthy donor stools compared to pre-FMT, 1 week post FMT, and 12 weeks post-FMT recipient stools.</measure>
    <time_frame>10 years</time_frame>
    <description>Fecal DNA samples will undergo shotgun DNA metagenomics sequencing. After removing human sequences, the Reads per kilobase gene length (RKP) will be calculated using HUMANN2 software for individual bacterial proteins/enzymes and pathways. . A linear mixed model will be used to compare RPK associated with pathways and individual proteins between each timepoint (FMT) and each disease group (Group). P-values less than 0.05 were considered as statistically significant.Linear mixed models analyses on the RPK associated with individual genes and pathways will be analyzed using linear mixed models between timepoints before and after FMT [pre-transplant recipient, 1-wk. post-FMT recipient, 3-mos. post-FMT recipient] and each disease group, a generalized linear mixed model (GLMM) or generalized estimating equation (GEE) were used by taking the actual RPK as the outcomes that will be assumed to follow a negative binomial distribution.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To measure the effect of fecal microbial transplantation on microbial function using bacterial metatranscriptomic sequencing</measure>
    <time_frame>10 years</time_frame>
    <description>Fecal RNA samples will undergo bacterial metatranscriptomic RNA sequencing. After removing human sequences, the Reads per kilobase transcript (RKP) will be calculated for individual bacterial proteins/enzymes and pathways. A linear mixed model will be used to compare RPK associated with pathways and individual proteins between each timepoint (FMT) and each disease group (Group). P-values less than 0.05 were considered as statistically significant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To measure the effect of fecal microbial transplantation on microbial function using targeted metabolomic assays.</measure>
    <time_frame>10 years</time_frame>
    <description>Fecal samples will undergo extraction for targeted metabolomics analysis of short chain fatty acids (micrograms/gram stool) using gas chromatography-mass spectrometry, and of bile acids (microgram/gram stool) using liquid chromatography-mass spectrometry. A linear mixed model will be used to compare respectively short chain fatty acid and bile acid metabolites between each timepoint (FMT) and each disease group (Group). P-values less than 0.05 were considered as statistically significant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine if FMT causes a statistically significant change in recipient fecal calprotectin levels</measure>
    <time_frame>10 years</time_frame>
    <description>Fecal calprotectin (microgram/gram stool) levels will be measured as in the recipient at baseline pre-FMT, 1 week, and 12 weeks post FMT. A linear mixed model will be used to compare fecal calprotectin levels between each timepoint (FMT) and each disease group (Group). P-values less than 0.05 were considered as statistically significant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine number of C. difficile recipients who have recurrent C. difficile within a year after fecal microbial transplant</measure>
    <time_frame>10 years</time_frame>
    <description>Currently the efficacy of colonoscopic FMT is approximately 90% after 12 weeks. However it may be lower with patients who also have inflammatory bowel disease. We will quantify the efficacy of fecal microbial transplant on C. difficile recurrence within a year in patients with C. difficile without inflammatory bowel diseases, C. difficile with Crohn's disease and C. difficile with ulcerative or indeterminate colitis.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Clostridium Difficile Infection</condition>
  <condition>Ulcerative Colitis</condition>
  <condition>Indeterminate Colitis</condition>
  <arm_group>
    <arm_group_label>Fecal microbial transplantation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treated with fecal microbial transplantation</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Fecal Microbial Transplantation</intervention_name>
    <description>Fecal microbial transplant is offered as treatment option to eligible patients. Donors selected by the patients will be screened by questionnaire and by blood and stool tests for potential transmissible pathogens.&#xD;
The stool filtrate will be administered in the ileum and/or cecum via colonoscopy</description>
    <arm_group_label>Fecal microbial transplantation</arm_group_label>
    <other_name>FMT</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        For C. difficile patients/recipients only:&#xD;
&#xD;
        Inclusion:&#xD;
&#xD;
        1. Patient is 7 years of age or older. 2. One of the following: 2a. At least two&#xD;
        recurrences (total three CDI infections) of mild to moderate C. difficile (&lt;6 diarrheal&#xD;
        stools/day) diagnosed by positive toxin PCR or EIA after completing standard medical&#xD;
        therapy with metronidazole, vancomycin or fidaxomicin.&#xD;
&#xD;
        2b. At least two episodes of severe C. difficile infection (&gt;6 diarrheal stools/day&#xD;
        requiring hospitalization and associated with significant morbidity).&#xD;
&#xD;
        2c. Moderate C. difficile infection (3-6 diarrheal stools/day not responding to successive&#xD;
        standard therapy, e.g. metronidazole, vancomycin and/or fidaxomicin) lasting at least 28&#xD;
        days.&#xD;
&#xD;
        2d. Severe and/or fulminant C. difficile colitis (&gt; 6 diarrheal stools/day) with no&#xD;
        response to standard therapy after 48 hours.&#xD;
&#xD;
        Exclusion:&#xD;
&#xD;
          1. younger than 7 year old&#xD;
&#xD;
          2. scheduled for abdominal surgery within the next 12 weeks&#xD;
&#xD;
          3. had major abdominal surgery within the past 3 months&#xD;
&#xD;
          4. pregnancy&#xD;
&#xD;
          5. Hemoglobin &lt; 6 g/dL&#xD;
&#xD;
          6. absolute neutrophil count less than 1500/mm3&#xD;
&#xD;
          7. known diagnosis of graft vs. host disease&#xD;
&#xD;
          8. used an investigational drug within the past 2 months&#xD;
&#xD;
          9. used a TNFα agonist within the past 2 weeks&#xD;
&#xD;
         10. diagnosed with Bacteremia within the past 4 weeks&#xD;
&#xD;
        For patients with ulcerative and indeterminate colitis only:&#xD;
&#xD;
        Inclusion:&#xD;
&#xD;
          1. Patient is 7 years of age or older.&#xD;
&#xD;
          2. One of the following:&#xD;
&#xD;
        2a. treated with steroid therapy for at least one month. 2b. treated with immunomodulatory&#xD;
        therapy for at least one month 2c. treated with biological therapy for at least one month.&#xD;
&#xD;
        Exclusion:&#xD;
&#xD;
          1. younger than 7 years old&#xD;
&#xD;
          2. scheduled for abdominal surgery within the next 12 weeks&#xD;
&#xD;
          3. had major abdominal surgery within the past 3 months&#xD;
&#xD;
          4. pregnancy&#xD;
&#xD;
          5. Hemoglobin &lt; 6 g/dL&#xD;
&#xD;
          6. absolute neutrophil count less than 1500/mm3&#xD;
&#xD;
          7. known diagnosis of graft vs. host disease&#xD;
&#xD;
          8. used an investigational drug within the past 2 months&#xD;
&#xD;
          9. used a TNFα agonist within the past 2 weeks&#xD;
&#xD;
         10. diagnosed with Bacteremia within the past 4 weeks&#xD;
&#xD;
         11. previous FMT&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>7 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anupama Chawla, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stony Brook Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stony Brook University Hospital</name>
      <address>
        <city>Stony Brook</city>
        <state>New York</state>
        <zip>11794</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Mintz M, Khair S, Grewal S, LaComb JF, Park J, Channer B, Rajapakse R, Bucobo JC, Buscaglia JM, Monzur F, Chawla A, Yang J, Robertson CE, Frank DN, Li E. Longitudinal microbiome analysis of single donor fecal microbiota transplantation in patients with recurrent Clostridium difficile infection and/or ulcerative colitis. PLoS One. 2018 Jan 31;13(1):e0190997. doi: 10.1371/journal.pone.0190997. eCollection 2018.</citation>
    <PMID>29385143</PMID>
  </results_reference>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>March 22, 2016</study_first_submitted>
  <study_first_submitted_qc>August 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 31, 2017</study_first_posted>
  <last_update_submitted>February 21, 2022</last_update_submitted>
  <last_update_submitted_qc>February 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 22, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stony Brook University</investigator_affiliation>
    <investigator_full_name>Anupama Chawla</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Clostridium Infections</mesh_term>
    <mesh_term>Colitis</mesh_term>
    <mesh_term>Colitis, Ulcerative</mesh_term>
    <mesh_term>Ulcer</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 25, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/13/NCT03268213/Prot_ICF_002.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03268213
org study id: 479696
nct id: NCT03268213
lead sponsor: 
has dmc: Yes
Fecal Microbiota Transplantation will be offered to eligible C. difficile patients (does not
      require Investigational New Drug designation) and to eligible ulcerative colitis or
      indeterminate colitis patients as Investigational New Drug treatment
The following hypothesis will be tested in this study:

        1. Fecal microbiota transplantation is a safe, tolerable, and efficacious procedure for C.
           difficile patients and is a safe and tolerable procedure for ulcerative colitis and
           indeterminate colitis patients.

        2. The fecal microbial diversity, composition and function in stool recipients after fecal
           transplantation will change to a similar microbial diversity, composition and
           functionality as found in donor stool.

      Primary objectives:

      1. To determine the short term safety and tolerability of fecal microbiota transplantation in
      patients with recurrent or refractory Clostridium difficile and medication refractory
      Ulcerative colitis or indeterminate colitis up to 12 weeks post-transplant.

      Secondary objectives:

      1a. To determine the long term safety and tolerability of fecal microbiota transplantation up
      to 1 year post-transplant in patients with recurrent or refractory Clostridium difficile and
      medication refractory Ulcerative colitis or indeterminate colitis.

      1b. To determine the efficacy of fecal microbiota transplantation in patients with recurrent
      or refractory Clostridium difficile defined as no recurrence of C. difficile within one year.

      2. To compare microbial diversity in healthy donor stools compared to pre-FMT recipient
      stools collected from patients (recipients) with recurrent or refractory Clostridium
      difficile and medication refractory Ulcerative colitis or indeterminate colitis.

      3. To compare microbial composition in healthy donor stools compared to pre-FMT recipient
      stools from patients (recipients) with recurrent or refractory Clostridium difficile and
      medication refractory Ulcerative colitis or indeterminate colitis.

      4. To compare microbial function in healthy donor stools compared to pre-FMT recipient stools
      from patients (recipients) with recurrent or refractory Clostridium difficile and medication
      refractory Ulcerative colitis or indeterminate colitis.

      5. To compare microbial diversity in healthy donor stools and pre-FMT recipient stools with 1
      week post-transplant recipient stool samples collected from patients (recipients) with
      recurrent or refractory Clostridium difficile and medication refractory Ulcerative colitis or
      indeterminate colitis.

      6. To compare microbial composition in healthy donor stools and pre-FMT recipient stools with
      1 week post-transplant recipient stool samples collected from patients (recipients) with
      recurrent or refractory Clostridium difficile and medication refractory Ulcerative colitis or
      indeterminate colitis.

      7. To compare microbial function in healthy donor stools and pre-FMT recipient stools with 1
      week post-transplant recipient stool samples collected from patients (recipients) with
      recurrent or refractory Clostridium difficile and medication refractory Ulcerative colitis or
      indeterminate colitis.

      8. To compare microbial diversity in healthy donor stools and pre-FMT recipient stools with
      12 week post transplant recipient stool samples collected from patients (recipients) with
      recurrent or refractory Clostridium difficile and medication refractory Ulcerative colitis or
      indeterminate colitis.

      9. To compare microbial composition in healthy donor stools and pre-FMT recipient stools with
      12 week post transplant recipient stool samples collected from patients (recipients) with
      recurrent or refractory Clostridium difficile and medication refractory Ulcerative colitis or
      indeterminate colitis.

      10. To compare microbial function in healthy donor stools and pre-FMT recipient stools with
      12 week post transplant recipient stool samples collected from patients (recipients) with
      recurrent or refractory Clostridium difficile and medication refractory Ulcerative colitis or
      indeterminate colitis.

      11. Stool calprotectin levels will be measured in the recipient at baseline pre-FMT, 1 week
      and 12 weeks post FMT to determine if FMT causes a statistically significant change.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: FMT is offered as a treatment to eligible patients
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
time frame: 9 years
description: Number of participants with treatment-related adverse events with grade greater than 2 within one year after FMT will be reported.
Safety will be assessed as a report of no new medical condition after the transplant, Tolerability, as recorded by report of no serious adverse events after the transplant and Efficacy of the procedure will be recorded as improvement in clinical symptoms during any clinically indicated colonoscopies after the transplant as compared to before transplant
C. Diff patients will have a negative C. diff test report after the transplant as an out come measure.
measure: To measure the effect of fecal microbial transplantation on microbial diversity in healthy donor stools compared to pre-FMT, 1 week post FMT, and 12 weeks post-FMT recipient stools.
time frame: 10 years
description: Fecal DNA samples will undergo V3-V4 16S rRNA sequencing. Operational taxonomic units (OTUs) will be produced by clustering sequences with identical taxonomic assignments. Alpha diversity indices (e.g. Chao1, Shannon complexity H, Shannon Evenness H/Hmax) will be calculated inferred through 1000 replicate resamplings using Explicet. Beta diversity (Bray-Curtis and Jaccard distances) will be calculated for the recipient Pre-FMT, 1 week post-FMT and 12 weeks post-FMT as compared to their pared donor using the adonis function in the R vegan package at the phyla, family and genus level. A linear mixed model will be used to compare alpha-diversity (ShannonH) and beta-diversity (Bray-Curtis and Jaccard distance) between each timepoint (FMT) and each disease group (Group). P-values less than 0.05 were considered as statistically significant.
measure: To measure the effect of fecal microbial transplantation on microbial composition in healthy donor stools compared to pre-FMT, 1 week post FMT, and 12 weeks post-FMT recipient stools.
time frame: 10 years
description: Fecal DNA samples will undergo V3-V4 16S rRNA sequencing. Operational taxonomic units (OTUs) will be produced by clustering sequences with identical taxonomic assignments. Linear mixed models analyses on individual OTUs at the genus level will be conducted on 105 OTUs after eliminating OTUs with an average relative abundance of < 0.001% in the donor and recipient pre-FMT samples, and after discarding OTUs where more than 75% of the samples had a zero count. To compare the relative abundance of each OTU between timepoints before and after FMT [pre-transplant recipient, 1-wk. post-FMT recipient, 3-mos. post-FMT recipient] and each disease group, a generalized linear mixed model (GLMM) or generalized estimating equation (GEE) will be used by taking the actual counts of each OTU as the outcomes that were assumed to follow a negative binomial distribution. The p-values will be adjusted for multiple comparisons by the Bonferroni correction or by the Benjamin-Hochberg method (FDR < 0.05).
measure: To measure the effect of fecal microbial transplantation on microbial function using shotgun DNA metagenomic in healthy donor stools compared to pre-FMT, 1 week post FMT, and 12 weeks post-FMT recipient stools.
time frame: 10 years
description: Fecal DNA samples will undergo shotgun DNA metagenomics sequencing. After removing human sequences, the Reads per kilobase gene length (RKP) will be calculated using HUMANN2 software for individual bacterial proteins/enzymes and pathways. . A linear mixed model will be used to compare RPK associated with pathways and individual proteins between each timepoint (FMT) and each disease group (Group). P-values less than 0.05 were considered as statistically significant.Linear mixed models analyses on the RPK associated with individual genes and pathways will be analyzed using linear mixed models between timepoints before and after FMT [pre-transplant recipient, 1-wk. post-FMT recipient, 3-mos. post-FMT recipient] and each disease group, a generalized linear mixed model (GLMM) or generalized estimating equation (GEE) were used by taking the actual RPK as the outcomes that will be assumed to follow a negative binomial distribution.
measure: To measure the effect of fecal microbial transplantation on microbial function using bacterial metatranscriptomic sequencing
time frame: 10 years
description: Fecal RNA samples will undergo bacterial metatranscriptomic RNA sequencing. After removing human sequences, the Reads per kilobase transcript (RKP) will be calculated for individual bacterial proteins/enzymes and pathways. A linear mixed model will be used to compare RPK associated with pathways and individual proteins between each timepoint (FMT) and each disease group (Group). P-values less than 0.05 were considered as statistically significant.
measure: To measure the effect of fecal microbial transplantation on microbial function using targeted metabolomic assays.
time frame: 10 years
description: Fecal samples will undergo extraction for targeted metabolomics analysis of short chain fatty acids (micrograms/gram stool) using gas chromatography-mass spectrometry, and of bile acids (microgram/gram stool) using liquid chromatography-mass spectrometry. A linear mixed model will be used to compare respectively short chain fatty acid and bile acid metabolites between each timepoint (FMT) and each disease group (Group). P-values less than 0.05 were considered as statistically significant.
measure: Determine if FMT causes a statistically significant change in recipient fecal calprotectin levels
time frame: 10 years
description: Fecal calprotectin (microgram/gram stool) levels will be measured as in the recipient at baseline pre-FMT, 1 week, and 12 weeks post FMT. A linear mixed model will be used to compare fecal calprotectin levels between each timepoint (FMT) and each disease group (Group). P-values less than 0.05 were considered as statistically significant.
measure: Determine number of C. difficile recipients who have recurrent C. difficile within a year after fecal microbial transplant
time frame: 10 years
description: Currently the efficacy of colonoscopic FMT is approximately 90% after 12 weeks. However it may be lower with patients who also have inflammatory bowel disease. We will quantify the efficacy of fecal microbial transplant on C. difficile recurrence within a year in patients with C. difficile without inflammatory bowel diseases, C. difficile with Crohn's disease and C. difficile with ulcerative or indeterminate colitis.
arm group label: Fecal microbial transplantation
arm group type: Experimental
description: Treated with fecal microbial transplantation
intervention type: Biological
intervention name: Fecal Microbial Transplantation
description: Fecal microbial transplant is offered as treatment option to eligible patients. Donors selected by the patients will be screened by questionnaire and by blood and stool tests for potential transmissible pathogens.
The stool filtrate will be administered in the ileum and/or cecum via colonoscopy
arm group label: Fecal microbial transplantation
other name: FMT
criteria: 
gender: All
minimum age: 7 Years
maximum age: N/A
healthy volunteers: No
last name: Anupama Chawla, MD
role: Principal Investigator
affiliation: Stony Brook Medicine
facility: 
country: United States
citation: Mintz M, Khair S, Grewal S, LaComb JF, Park J, Channer B, Rajapakse R, Bucobo JC, Buscaglia JM, Monzur F, Chawla A, Yang J, Robertson CE, Frank DN, Li E. Longitudinal microbiome analysis of single donor fecal microbiota transplantation in patients with recurrent Clostridium difficile infection and/or ulcerative colitis. PLoS One. 2018 Jan 31;13(1):e0190997. doi: 10.1371/journal.pone.0190997. eCollection 2018.
PMID: 29385143
responsible party type: Principal Investigator
investigator affiliation: Stony Brook University
investigator full name: Anupama Chawla
investigator title: Professor
mesh term: Clostridium Infections
mesh term: Colitis
mesh term: Colitis, Ulcerative
mesh term: Ulcer
sharing ipd: No
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