<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/NCT03273465</url>
  </required_header>
  <id_info>
    <org_study_id>0268-16-ASF</org_study_id>
    <nct_id>NCT03273465</nct_id>
  </id_info>
  <brief_title>Fecal Microbiota Transplantation in Ulcerative Colitis</brief_title>
  <official_title>Fecal Microbiota Transplantation in Newly Diagnosed Patients With Ulcerative Colitis - a Double Blind, Placebo-Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assaf-Harofeh Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assaf-Harofeh Medical Center</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Fecal Microbiota Transplantation(FMT) - reconstitution of normal flora by a stool transplant&#xD;
      from a healthy individual, is increasingly being recognized as a therapeutic modality for&#xD;
      diseases that are associated with gut dysbiosis.&#xD;
&#xD;
      This is a placebo-controlled, double blinded interventional study evaluating multiple, oral,&#xD;
      fecal microbiota transplantation, administered in newly diagnosed adult patients with&#xD;
      mild-moderate UC.&#xD;
&#xD;
      The primary objective is to assess the safety and feasibility of multiple, oral, fecal&#xD;
      microbiota transplantation,in newly diagnosed adult patients with mild-moderate UC.&#xD;
&#xD;
      All processing will occur at the Center for Microbiome Research at Assaf Harofeh Medical&#xD;
      Center, under GMP conditions.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 27, 2017</start_date>
  <completion_date type="Anticipated">April 2021</completion_date>
  <primary_completion_date type="Anticipated">April 2020</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>
    <intervention_model_description>This is a placebo-controlled, double blinded interventional study evaluating oral, fecal microbiota transplantation, administered in patients with mild-moderate UC.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>Double Blind (Subject, Caregiver, Investigator)</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>UC remission</measure>
    <time_frame>12 weeks</time_frame>
    <description>UC remission at week 12 defined as a Simple Clinical Colitis Activity Index&lt;3</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Improvement in UC symptoms</measure>
    <time_frame>12 weeks</time_frame>
    <description>defined as improvement in SCCAI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement in UC endoscopic score</measure>
    <time_frame>12 weeks, 6 months and 12 months</time_frame>
    <description>Mayo-score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>markers of inflammation</measure>
    <time_frame>12 weeks, 6 months and 12 months</time_frame>
    <description>Laboratory markers of inflammation - CRP, WBC, ANC, stool calprotectin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in gut microbiome</measure>
    <time_frame>12 weeks, 6 and 12 months.</time_frame>
    <description>Diversity and variability of gut microbiome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>use of treatments for UC</measure>
    <time_frame>6+12 months</time_frame>
    <description>such as glucocorticoids, immunosuppressive therapy (eg, azathioprine), or tumor necrosis factor antagonists.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Extra-intestinal disease manifestations</measure>
    <time_frame>6 and 12 month</time_frame>
    <description>Extra-intestinal disease manifestations</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Ulcerative Colitis</condition>
  <arm_group>
    <arm_group_label>Fecal transplantation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Fecal transplantation of feces from healthy donor via capsules. Oral application.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo capsules</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Fecal transplantation</intervention_name>
    <description>Fecal transplantation administered orally via frozen capsules.</description>
    <arm_group_label>Fecal transplantation</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women of child-bearing potential and men must agree to use adequate contraception&#xD;
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for&#xD;
             the duration of study participation. Should a woman become pregnant or suspect she is&#xD;
             pregnant while she or her partner is participating in this study, she should inform&#xD;
             her treating physician immediately. Women of childbearing potential will have a urine&#xD;
             pregnancy test, which must be negative, on Study Day 1, prior to receiving FMT. Men&#xD;
             treated or enrolled on this protocol must also agree to use adequate contraception&#xD;
             prior to the study and for 3 months after FMT.&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document,&#xD;
             including the willingness to accept risk of unrelated donor stool.&#xD;
&#xD;
          -  Ability to swallow oral medications.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe, uncontrolled ulcerative colitis.&#xD;
&#xD;
          -  Patients with active or uncontrolled bacterial, viral, or fungal infection(s)&#xD;
             requiring systemic therapy.&#xD;
&#xD;
          -  Delayed gastric emptying syndrome&#xD;
&#xD;
          -  Known chronic aspiration&#xD;
&#xD;
          -  Patients with a history of significant allergy to foods not excluded from the donor&#xD;
             diet (excluded foods are tree nuts, peanuts, shellfish, eggs)&#xD;
&#xD;
          -  Pregnant and breast-feeding women&#xD;
&#xD;
          -  Participants who are unable to swallow pills.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Ilan Youngster, Dr.</last_name>
    <phone>972-50-6301191</phone>
    <email>yongsteri@asaf.health.gov.il</email>
  </overall_contact>
  <location>
    <facility>
      <name>Assaf-HarofehMC</name>
      <address>
        <city>Zerifin</city>
        <zip>70300</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ilan Youngster, Dr.</last_name>
      <phone>972-50-6301191</phone>
      <email>youngsteri@asaf.health.gov.il</email>
    </contact>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <reference>
    <citation>Drekonja D, Reich J, Gezahegn S, Greer N, Shaukat A, MacDonald R, Rutks I, Wilt TJ. Fecal Microbiota Transplantation for Clostridium difficile Infection: A Systematic Review. Ann Intern Med. 2015 May 5;162(9):630-8. doi: 10.7326/M14-2693.</citation>
    <PMID>25938992</PMID>
  </reference>
  <reference>
    <citation>Li SS, Zhu A, Benes V, Costea PI, Hercog R, Hildebrand F, Huerta-Cepas J, Nieuwdorp M, Salojarvi J, Voigt AY, Zeller G, Sunagawa S, de Vos WM, Bork P. Durable coexistence of donor and recipient strains after fecal microbiota transplantation. Science. 2016 Apr 29;352(6285):586-9. doi: 10.1126/science.aad8852.</citation>
    <PMID>27126044</PMID>
  </reference>
  <reference>
    <citation>Rossen NG, MacDonald JK, de Vries EM, D'Haens GR, de Vos WM, Zoetendal EG, Ponsioen CY. Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review. World J Gastroenterol. 2015 May 7;21(17):5359-71. doi: 10.3748/wjg.v21.i17.5359.</citation>
    <PMID>25954111</PMID>
  </reference>
  <reference>
    <citation>Khoruts A, Sadowsky MJ. Understanding the mechanisms of faecal microbiota transplantation. Nat Rev Gastroenterol Hepatol. 2016 Sep;13(9):508-16. doi: 10.1038/nrgastro.2016.98. Epub 2016 Jun 22.</citation>
    <PMID>27329806</PMID>
  </reference>
  <reference>
    <citation>Drekonja D, Reich J, Gezahegn S, Greer N, Shaukat A, MacDonald R, Rutks I, Wilt T. Fecal Microbiota Transplantation for Clostridium Difficile Infection: A Systematic Review of the Evidence [Internet]. Washington (DC): Department of Veterans Affairs (US); 2014 Jul. Available from http://www.ncbi.nlm.nih.gov/books/NBK299000/</citation>
    <PMID>26042318</PMID>
  </reference>
  <reference>
    <citation>Scaldaferri F, Pecere S, Petito V, Zambrano D, Fiore L, Lopetuso LR, Schiavoni E, Bruno G, Gerardi V, Laterza L, Pizzoferrato M, Ianiro G, Stojanovic J, Poscia A, Papa A, Paroni Sterbini F, Sanguinetti M, Masucci L, Cammarota G, Gasbarrini A. Efficacy and Mechanisms of Action of Fecal Microbiota Transplantation in Ulcerative Colitis: Pitfalls and Promises From a First Meta-Analysis. Transplant Proc. 2016 Mar;48(2):402-7. doi: 10.1016/j.transproceed.2015.12.040. Erratum In: Transplant Proc. 2018 Jan - Feb;50(1):305.</citation>
    <PMID>27109966</PMID>
  </reference>
  <reference>
    <citation>Moayyedi P, Surette MG, Kim PT, Libertucci J, Wolfe M, Onischi C, Armstrong D, Marshall JK, Kassam Z, Reinisch W, Lee CH. Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial. Gastroenterology. 2015 Jul;149(1):102-109.e6. doi: 10.1053/j.gastro.2015.04.001. Epub 2015 Apr 7.</citation>
    <PMID>25857665</PMID>
  </reference>
  <reference>
    <citation>Rossen NG, Fuentes S, van der Spek MJ, Tijssen JG, Hartman JH, Duflou A, Lowenberg M, van den Brink GR, Mathus-Vliegen EM, de Vos WM, Zoetendal EG, D'Haens GR, Ponsioen CY. Findings From a Randomized Controlled Trial of Fecal Transplantation for Patients With Ulcerative Colitis. Gastroenterology. 2015 Jul;149(1):110-118.e4. doi: 10.1053/j.gastro.2015.03.045. Epub 2015 Mar 30.</citation>
    <PMID>25836986</PMID>
  </reference>
  <reference>
    <citation>Youngster I, Russell GH, Pindar C, Ziv-Baran T, Sauk J, Hohmann EL. Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection. JAMA. 2014 Nov 5;312(17):1772-8. doi: 10.1001/jama.2014.13875. Erratum In: JAMA. 2015 Feb 17;313(7):729.</citation>
    <PMID>25322359</PMID>
  </reference>
  <reference>
    <citation>Kelly CR, Ihunnah C, Fischer M, Khoruts A, Surawicz C, Afzali A, Aroniadis O, Barto A, Borody T, Giovanelli A, Gordon S, Gluck M, Hohmann EL, Kao D, Kao JY, McQuillen DP, Mellow M, Rank KM, Rao K, Ray A, Schwartz MA, Singh N, Stollman N, Suskind DL, Vindigni SM, Youngster I, Brandt L. Fecal microbiota transplant for treatment of Clostridium difficile infection in immunocompromised patients. Am J Gastroenterol. 2014 Jul;109(7):1065-71. doi: 10.1038/ajg.2014.133. Epub 2014 Jun 3.</citation>
    <PMID>24890442</PMID>
  </reference>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>September 4, 2017</study_first_submitted>
  <study_first_submitted_qc>September 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 6, 2017</study_first_posted>
  <last_update_submitted>September 5, 2017</last_update_submitted>
  <last_update_submitted_qc>September 5, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Assaf-Harofeh Medical Center</investigator_affiliation>
    <investigator_full_name>Assaf Harofeh MC</investigator_full_name>
    <investigator_title>Dr.</investigator_title>
  </responsible_party>
  <keyword>IBD</keyword>
  <keyword>Colitis</keyword>
  <keyword>fecal</keyword>
  <keyword>FMT</keyword>
  <keyword>microbiota</keyword>
  <keyword>transplantation</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>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <study_docs>
    <study_doc>
      <doc_type>Clinical Study Report</doc_type>
      <doc_url>https://www.ncbi.nlm.nih.gov/pubmed/25938992</doc_url>
    </study_doc>
  </study_docs>
  <!-- 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/NCT03273465
org study id: 0268-16-ASF
nct id: NCT03273465
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Fecal Microbiota Transplantation(FMT) - reconstitution of normal flora by a stool transplant
      from a healthy individual, is increasingly being recognized as a therapeutic modality for
      diseases that are associated with gut dysbiosis.

      This is a placebo-controlled, double blinded interventional study evaluating multiple, oral,
      fecal microbiota transplantation, administered in newly diagnosed adult patients with
      mild-moderate UC.

      The primary objective is to assess the safety and feasibility of multiple, oral, fecal
      microbiota transplantation,in newly diagnosed adult patients with mild-moderate UC.

      All processing will occur at the Center for Microbiome Research at Assaf Harofeh Medical
      Center, under GMP conditions.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a placebo-controlled, double blinded interventional study evaluating oral, fecal microbiota transplantation, administered in patients with mild-moderate UC.
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: Double Blind (Subject, Caregiver, Investigator)
measure: UC remission
time frame: 12 weeks
description: UC remission at week 12 defined as a Simple Clinical Colitis Activity Index<3
measure: Improvement in UC symptoms
time frame: 12 weeks
description: defined as improvement in SCCAI
measure: Improvement in UC endoscopic score
time frame: 12 weeks, 6 months and 12 months
description: Mayo-score
measure: markers of inflammation
time frame: 12 weeks, 6 months and 12 months
description: Laboratory markers of inflammation - CRP, WBC, ANC, stool calprotectin
measure: change in gut microbiome
time frame: 12 weeks, 6 and 12 months.
description: Diversity and variability of gut microbiome
measure: use of treatments for UC
time frame: 6+12 months
description: such as glucocorticoids, immunosuppressive therapy (eg, azathioprine), or tumor necrosis factor antagonists.
measure: Extra-intestinal disease manifestations
time frame: 6 and 12 month
description: Extra-intestinal disease manifestations
arm group label: Fecal transplantation
arm group type: Experimental
description: Fecal transplantation of feces from healthy donor via capsules. Oral application.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo capsules
intervention type: Other
intervention name: Fecal transplantation
description: Fecal transplantation administered orally via frozen capsules.
arm group label: Fecal transplantation
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: No
last name: Ilan Youngster, Dr.
phone: 972-50-6301191
email: yongsteri@asaf.health.gov.il
facility: 
status: Recruiting
contact: 
country: Israel
citation: Drekonja D, Reich J, Gezahegn S, Greer N, Shaukat A, MacDonald R, Rutks I, Wilt TJ. Fecal Microbiota Transplantation for Clostridium difficile Infection: A Systematic Review. Ann Intern Med. 2015 May 5;162(9):630-8. doi: 10.7326/M14-2693.
PMID: 25938992
citation: Li SS, Zhu A, Benes V, Costea PI, Hercog R, Hildebrand F, Huerta-Cepas J, Nieuwdorp M, Salojarvi J, Voigt AY, Zeller G, Sunagawa S, de Vos WM, Bork P. Durable coexistence of donor and recipient strains after fecal microbiota transplantation. Science. 2016 Apr 29;352(6285):586-9. doi: 10.1126/science.aad8852.
PMID: 27126044
citation: Rossen NG, MacDonald JK, de Vries EM, D'Haens GR, de Vos WM, Zoetendal EG, Ponsioen CY. Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review. World J Gastroenterol. 2015 May 7;21(17):5359-71. doi: 10.3748/wjg.v21.i17.5359.
PMID: 25954111
citation: Khoruts A, Sadowsky MJ. Understanding the mechanisms of faecal microbiota transplantation. Nat Rev Gastroenterol Hepatol. 2016 Sep;13(9):508-16. doi: 10.1038/nrgastro.2016.98. Epub 2016 Jun 22.
PMID: 27329806
citation: Drekonja D, Reich J, Gezahegn S, Greer N, Shaukat A, MacDonald R, Rutks I, Wilt T. Fecal Microbiota Transplantation for Clostridium Difficile Infection: A Systematic Review of the Evidence [Internet]. Washington (DC): Department of Veterans Affairs (US); 2014 Jul. Available from http://www.ncbi.nlm.nih.gov/books/NBK299000/
PMID: 26042318
citation: Scaldaferri F, Pecere S, Petito V, Zambrano D, Fiore L, Lopetuso LR, Schiavoni E, Bruno G, Gerardi V, Laterza L, Pizzoferrato M, Ianiro G, Stojanovic J, Poscia A, Papa A, Paroni Sterbini F, Sanguinetti M, Masucci L, Cammarota G, Gasbarrini A. Efficacy and Mechanisms of Action of Fecal Microbiota Transplantation in Ulcerative Colitis: Pitfalls and Promises From a First Meta-Analysis. Transplant Proc. 2016 Mar;48(2):402-7. doi: 10.1016/j.transproceed.2015.12.040. Erratum In: Transplant Proc. 2018 Jan - Feb;50(1):305.
PMID: 27109966
citation: Moayyedi P, Surette MG, Kim PT, Libertucci J, Wolfe M, Onischi C, Armstrong D, Marshall JK, Kassam Z, Reinisch W, Lee CH. Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial. Gastroenterology. 2015 Jul;149(1):102-109.e6. doi: 10.1053/j.gastro.2015.04.001. Epub 2015 Apr 7.
PMID: 25857665
citation: Rossen NG, Fuentes S, van der Spek MJ, Tijssen JG, Hartman JH, Duflou A, Lowenberg M, van den Brink GR, Mathus-Vliegen EM, de Vos WM, Zoetendal EG, D'Haens GR, Ponsioen CY. Findings From a Randomized Controlled Trial of Fecal Transplantation for Patients With Ulcerative Colitis. Gastroenterology. 2015 Jul;149(1):110-118.e4. doi: 10.1053/j.gastro.2015.03.045. Epub 2015 Mar 30.
PMID: 25836986
citation: Youngster I, Russell GH, Pindar C, Ziv-Baran T, Sauk J, Hohmann EL. Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection. JAMA. 2014 Nov 5;312(17):1772-8. doi: 10.1001/jama.2014.13875. Erratum In: JAMA. 2015 Feb 17;313(7):729.
PMID: 25322359
citation: Kelly CR, Ihunnah C, Fischer M, Khoruts A, Surawicz C, Afzali A, Aroniadis O, Barto A, Borody T, Giovanelli A, Gordon S, Gluck M, Hohmann EL, Kao D, Kao JY, McQuillen DP, Mellow M, Rank KM, Rao K, Ray A, Schwartz MA, Singh N, Stollman N, Suskind DL, Vindigni SM, Youngster I, Brandt L. Fecal microbiota transplant for treatment of Clostridium difficile infection in immunocompromised patients. Am J Gastroenterol. 2014 Jul;109(7):1065-71. doi: 10.1038/ajg.2014.133. Epub 2014 Jun 3.
PMID: 24890442
responsible party type: Principal Investigator
investigator affiliation: Assaf-Harofeh Medical Center
investigator full name: Assaf Harofeh MC
investigator title: Dr.
mesh term: Colitis
mesh term: Colitis, Ulcerative
mesh term: Ulcer
sharing ipd: Undecided
study doc: 