<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/NCT03006809</url>
  </required_header>
  <id_info>
    <org_study_id>16-20066</org_study_id>
    <nct_id>NCT03006809</nct_id>
  </id_info>
  <brief_title>Optimal Fecal Microbiota Transplant Dosing for Mild to Moderate Ulcerative Colitis</brief_title>
  <official_title>Optimal Fecal Microbiota Transplant Dosing for Mild to Moderate Ulcerative Colitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Najwa Elnachef</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of California, San Francisco</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a prospective unblinded, randomized trial for the use of Fecal Microbiota&#xD;
      Transplantation (FMT) for the treatment of Ulcerative Colitis (UC), in combination with or&#xD;
      without antibiotic pretreatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective open-label, randomized trial for the use of Fecal Microbiota&#xD;
      Transplantation (FMT) for the treatment of Ulcerative Colitis (UC), in combination with or&#xD;
      without antibiotic pretreatment.&#xD;
&#xD;
      This trial involves 11 study visits at UCSF in San Francisco, CA.&#xD;
&#xD;
      The routes of administration will be via colonoscopy for all subjects with maintenance&#xD;
      therapy administered orally (i.e. using encapsulated FMT) for half of the subjects and per&#xD;
      rectum by enema in the other half of the subjects. Additionally, the utility of pretreatment&#xD;
      antibiotics will be assessed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 2, 2017</start_date>
  <completion_date type="Actual">April 4, 2021</completion_date>
  <primary_completion_date type="Actual">May 4, 2020</primary_completion_date>
  <phase>Phase 1</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The occurrence of a Serious Adverse event (SAE), solicited and unsolicited AE, new gastrointestinal medical condition and diagnoses from FMT treatment or new infection from FMT treatment</measure>
    <time_frame>up to 1 year</time_frame>
    <description>safety endpoint</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Steroid-free Clinical Remission at week 9 + endoscopic remission or response defined as total Mayo score ≤ 2 with all four sub-scores ≤ 1 and a ≥ 1 point reduction in endoscopy sub-score</measure>
    <time_frame>8 weeks post initial treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in microbiome with FMT therapy. Changes in the microbiome: assessed by frequent stool sampling for 16S rRNA analysis prior to each FMT therapy and after the last capsule/enema dose</measure>
    <time_frame>up to 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Response: decrease in Mayo score by ≥ 3 points, decrease in bleeding subscore by ≥ 1, or absolute subscore of 0-1</measure>
    <time_frame>8 weeks post initial treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression of disease defined by initiation of anti-TNF agents or Corticosteroids: Initiation of anti-TNF agents (such as infliximab, adalimumab, certolizumab, vedolizumab and steroids). Includes time gap until additional agents are started.</measure>
    <time_frame>2, 4 and 8 weeks post initial FMT</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression of disease defined by increase in dosages of current UC medications</measure>
    <time_frame>2, 4 and 8 weeks post initial FMT</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression of disease defined by time to colectomy</measure>
    <time_frame>up to one year post initial FMT</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to death secondary to UC</measure>
    <time_frame>up to one year post initial FMT</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression of disease defined by clinical flare (Time to next flare)</measure>
    <time_frame>2, 4 and 8 weeks post initial FMT</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Increase in Quality of Life (based on RAND SF-36 survey and score)</measure>
    <time_frame>8 weeks post initial FMT</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Mood/Depression Score (based on PHQ-9 survey and score)</measure>
    <time_frame>8 weeks post initial FMT</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Ulcerative Colitis</condition>
  <arm_group>
    <arm_group_label>1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>pretreatment antibiotics + FMT delivered by colonoscopy + FMT capsules per week x 6 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>no antibiotics, FMT delivered by colonoscopy + FMT capsules per week x 6 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>pretreatment antibiotics + FMT delivered by colonoscopy + FMT delivered by enema once per week x 6 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>no antibiotics, FMT delivered by colonoscopy + FMT delivered by enema once per week x 6 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Fecal Microbiota Transplantation (FMT), OpenBiome</intervention_name>
    <description>Delivered by colonoscopy, enema or orally (as capsules)</description>
    <arm_group_label>1</arm_group_label>
    <arm_group_label>2</arm_group_label>
    <arm_group_label>3</arm_group_label>
    <arm_group_label>4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>pretreatment antibiotics</intervention_name>
    <description>5 day course (vancomycin PO 500mg bid, metronidazole PO 500mg bid, and neomycin PO 500mg bid) starting 6 days prior FMT</description>
    <arm_group_label>1</arm_group_label>
    <arm_group_label>3</arm_group_label>
    <other_name>vancomycin, metronidazole, neomycin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with history of mild to moderate Ulcerative Colitis confirmed by endoscopy&#xD;
             and pathology.&#xD;
&#xD;
          -  Total Mayo score 4-9, endoscopic subscore ≥1; patients who have not had endoscopic&#xD;
             evaluation within one year of enrollment will have flexible sigmoidoscopy for&#xD;
             evaluation.&#xD;
&#xD;
          -  Age 18 - 64 and deemed otherwise healthy at the discretion of the investigator.&#xD;
&#xD;
          -  Concurrent therapies with mesalamine (stable x 4 weeks), immunomodulators (stable x 3&#xD;
             months), and biologic agents (stable x 3 months) will be allowed to continue during&#xD;
             study.&#xD;
&#xD;
          -  If patient is on prednisone, the dose must be ≤ 10mg/day at the time of treatment and&#xD;
             will be weaned by 2.5mg/week during the study period.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe or refractory UC defined as Mayo score ≥10, endoscopic disease activity score 3&#xD;
&#xD;
          -  Untreated enteric infection (positive stool test for any of the following: Clostridium&#xD;
             difficile, Salmonella, Shigella, Yersinia, Campylobacter, enteropathogenic E. coli or&#xD;
             other enteric infection at the discretion of the investigator.&#xD;
&#xD;
          -  History of colectomy&#xD;
&#xD;
          -  Disease limited to distal proctitis&#xD;
&#xD;
          -  Patients taking probiotics within 6 weeks of planned FMT therapy.&#xD;
&#xD;
          -  Severe immunodeficiency, inherited or acquired (e.g. HIV, chemotherapy or radiation&#xD;
             therapy)&#xD;
&#xD;
          -  Patients with the following laboratory abnormalities: absolute neutrophil count (ANC)&#xD;
             &lt; 1000 / µl, platelets &lt;50 x 10^9 /L,, hemoglobin &lt;6.5 g/dL..&#xD;
&#xD;
          -  History of anaphylaxis (severe allergic reaction) to food allergens (e.g. tree nuts,&#xD;
             shellfish)&#xD;
&#xD;
          -  Dysphagia (oropharyngeal, esophageal, functional, neuromuscular)&#xD;
&#xD;
          -  History of recurrent aspiration episodes&#xD;
&#xD;
          -  Documented severe gastroparesis&#xD;
&#xD;
          -  Active intestinal obstruction&#xD;
&#xD;
          -  Patients with renal insufficiency (GFR &lt; 50ml/min)&#xD;
&#xD;
          -  Allergy to the following generally regarded as safe ingredients (GRAS): glycerol, acid&#xD;
             resistant HPMC, gellan gum, cocoa butter, titanium dioxide&#xD;
&#xD;
          -  Adverse event attributable to any previous FMT&#xD;
&#xD;
          -  Allergy/intolerance to proton pump inhibitor therapy&#xD;
&#xD;
          -  Allergy/intolerance to vancomycin, metronidazole, or neomycin.&#xD;
&#xD;
          -  Non-steroidal inflammatory medications (NSAIDs) as long-term treatment, defined as use&#xD;
             for at least 4 days a week each month.&#xD;
&#xD;
          -  Cholestyramine use&#xD;
&#xD;
          -  Any condition in which the investigator thinks the FMT treatment may pose a health&#xD;
             risk (e.g. severely immunocompromised)&#xD;
&#xD;
          -  Simultaneous participation in another interventional clinical trial&#xD;
&#xD;
          -  Patients who are pregnant, breast feeding or planning pregnancy during study trial&#xD;
             period.&#xD;
&#xD;
          -  During the trial period until one week after the trial end: Non-use of appropriate&#xD;
             contraceptives in females of childbearing potential (e.g. condoms, intrauterine device&#xD;
             (IUD), hormonal contraception, or other means considered adequate by the responsible&#xD;
             investigator) or in males with a child-fathering potential (condoms, or other means&#xD;
             considered adequate by the responsible investigator during treatment) or well-founded&#xD;
             doubt about the patient's cooperation&#xD;
&#xD;
          -  Patients with any other significant medical condition that could confound or interfere&#xD;
             with evaluation of safety, tolerability or prevent compliance with the study protocol&#xD;
             at the discretion of the investigator&#xD;
&#xD;
          -  Life expectancy &lt;6 months&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>64 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>UCSF Division of Gastroenterology at Mount Zion</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>December 21, 2016</study_first_submitted>
  <study_first_submitted_qc>December 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 30, 2016</study_first_posted>
  <last_update_submitted>April 26, 2021</last_update_submitted>
  <last_update_submitted_qc>April 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of California, San Francisco</investigator_affiliation>
    <investigator_full_name>Najwa Elnachef</investigator_full_name>
    <investigator_title>Assistant Clinical Professor</investigator_title>
  </responsible_party>
  <keyword>Ulcerative colitis</keyword>
  <keyword>FMT</keyword>
  <keyword>fecal transplant</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colitis</mesh_term>
    <mesh_term>Colitis, Ulcerative</mesh_term>
    <mesh_term>Ulcer</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anti-Bacterial Agents</mesh_term>
    <mesh_term>Metronidazole</mesh_term>
    <mesh_term>Vancomycin</mesh_term>
    <mesh_term>Neomycin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03006809
org study id: 16-20066
nct id: NCT03006809
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a prospective unblinded, randomized trial for the use of Fecal Microbiota
      Transplantation (FMT) for the treatment of Ulcerative Colitis (UC), in combination with or
      without antibiotic pretreatment.
This is a prospective open-label, randomized trial for the use of Fecal Microbiota
      Transplantation (FMT) for the treatment of Ulcerative Colitis (UC), in combination with or
      without antibiotic pretreatment.

      This trial involves 11 study visits at UCSF in San Francisco, CA.

      The routes of administration will be via colonoscopy for all subjects with maintenance
      therapy administered orally (i.e. using encapsulated FMT) for half of the subjects and per
      rectum by enema in the other half of the subjects. Additionally, the utility of pretreatment
      antibiotics will be assessed.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The occurrence of a Serious Adverse event (SAE), solicited and unsolicited AE, new gastrointestinal medical condition and diagnoses from FMT treatment or new infection from FMT treatment
time frame: up to 1 year
description: safety endpoint
measure: Steroid-free Clinical Remission at week 9 + endoscopic remission or response defined as total Mayo score ≤ 2 with all four sub-scores ≤ 1 and a ≥ 1 point reduction in endoscopy sub-score
time frame: 8 weeks post initial treatment
measure: Changes in microbiome with FMT therapy. Changes in the microbiome: assessed by frequent stool sampling for 16S rRNA analysis prior to each FMT therapy and after the last capsule/enema dose
time frame: up to 1 year
measure: Clinical Response: decrease in Mayo score by ≥ 3 points, decrease in bleeding subscore by ≥ 1, or absolute subscore of 0-1
time frame: 8 weeks post initial treatment
measure: Progression of disease defined by initiation of anti-TNF agents or Corticosteroids: Initiation of anti-TNF agents (such as infliximab, adalimumab, certolizumab, vedolizumab and steroids). Includes time gap until additional agents are started.
time frame: 2, 4 and 8 weeks post initial FMT
measure: Progression of disease defined by increase in dosages of current UC medications
time frame: 2, 4 and 8 weeks post initial FMT
measure: Progression of disease defined by time to colectomy
time frame: up to one year post initial FMT
measure: Time to death secondary to UC
time frame: up to one year post initial FMT
measure: Progression of disease defined by clinical flare (Time to next flare)
time frame: 2, 4 and 8 weeks post initial FMT
measure: Increase in Quality of Life (based on RAND SF-36 survey and score)
time frame: 8 weeks post initial FMT
measure: Changes in Mood/Depression Score (based on PHQ-9 survey and score)
time frame: 8 weeks post initial FMT
arm group label: 1
arm group type: Experimental
description: pretreatment antibiotics + FMT delivered by colonoscopy + FMT capsules per week x 6 weeks
arm group label: 2
arm group type: Experimental
description: no antibiotics, FMT delivered by colonoscopy + FMT capsules per week x 6 weeks
arm group label: 3
arm group type: Experimental
description: pretreatment antibiotics + FMT delivered by colonoscopy + FMT delivered by enema once per week x 6 weeks
arm group label: 4
arm group type: Experimental
description: no antibiotics, FMT delivered by colonoscopy + FMT delivered by enema once per week x 6 weeks
intervention type: Biological
intervention name: Fecal Microbiota Transplantation (FMT), OpenBiome
description: Delivered by colonoscopy, enema or orally (as capsules)
arm group label: 1
arm group label: 2
arm group label: 3
arm group label: 4
intervention type: Other
intervention name: pretreatment antibiotics
description: 5 day course (vancomycin PO 500mg bid, metronidazole PO 500mg bid, and neomycin PO 500mg bid) starting 6 days prior FMT
arm group label: 1
arm group label: 3
other name: vancomycin, metronidazole, neomycin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 64 Years
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of California, San Francisco
investigator full name: Najwa Elnachef
investigator title: Assistant Clinical Professor
mesh term: Colitis
mesh term: Colitis, Ulcerative
mesh term: Ulcer
mesh term: Anti-Bacterial Agents
mesh term: Metronidazole
mesh term: Vancomycin
mesh term: Neomycin
sharing ipd: No