<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/NCT03275467</url>
  </required_header>
  <id_info>
    <org_study_id>2017/072</org_study_id>
    <nct_id>NCT03275467</nct_id>
  </id_info>
  <brief_title>Faecal Microbiota Transplantation in Patients With Microscopic Colitis</brief_title>
  <official_title>Faecal Microbiota Transplantation in Patients With Microscopic Colitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Örebro University, Sweden</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Region Örebro County</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Örebro University, Sweden</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>
      Microscopic colitis (MC) is a disease with chronic inflammation of the colon that is mostly&#xD;
      diagnosed in middle-aged or elderly women. Patients suffer from chronic watery diarrhoea,&#xD;
      abdominal pain and weight loss. The aetiology of MC is still unknown but it is hypothesized&#xD;
      that MC is caused by a deregulated immune response to a luminal agent in predisposed&#xD;
      individuals, and an important role of the intestinal microbiota is suggested.&#xD;
&#xD;
      In the current proof-of-concept study, the effect of faecal microbiota transfer (FMT) in 10&#xD;
      MC patients will be evaluated. FMT consists in the infusion of suspended stool from a healthy&#xD;
      donor into the intestine of a patient with the aim to restore a disturbed intestinal&#xD;
      microbiota.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be an intervention pilot study with a 12-week and an optional 6-months follow-up&#xD;
      period. It will be investigated if the infusion of suspended stool from healthy donors&#xD;
      improves the symptoms of MC patients by restoring their disturbed intestinal microbiota. This&#xD;
      procedure is known as faecal microbiota transplantation (FMT).&#xD;
&#xD;
      MC patients (n=10) will be randomised to receive FMT using stool from one of two healthy&#xD;
      donors.&#xD;
&#xD;
      At baseline, blood samples and mucosal biopsies will be obtained from the descending colon.&#xD;
      In addition, faecal samples will be collected and patients will complete symptom&#xD;
      questionnaires. The first FMT will be administered by colonoscopy, FMT 2-3 by enemas. Faecal&#xD;
      samples will be collected and questionnaires will be completed at different time points&#xD;
      during the study. The patients will be followed-up at 6 weeks, 8 weeks, 12 weeks and 6 months&#xD;
      after receiving FMT 1, however, the follow-up after 6 months will be optional. Additional&#xD;
      biopsies from the descending colon and blood samples will be collected 6 weeks after the&#xD;
      first FMT.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2017</start_date>
  <completion_date type="Actual">October 31, 2019</completion_date>
  <primary_completion_date type="Actual">June 5, 2019</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of MC patients in remission six weeks after the first FMT.</measure>
    <time_frame>6 weeks</time_frame>
    <description>Remission is defined as &lt;3 stools per day and a mean of less than one watery stool per day.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in general health and symptom questionnaire scores</measure>
    <time_frame>6 weeks, 8 weeks, 12 weeks, 6 months</time_frame>
    <description>SHS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in general health questionnaire scores</measure>
    <time_frame>6 weeks, 8 weeks, 12 weeks, 6 months</time_frame>
    <description>SF-36</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in quality of life questionnaire scores</measure>
    <time_frame>6 weeks, 8 weeks, 12 weeks, 6 months</time_frame>
    <description>EG-5D-5L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in gastrointestinal symptom questionnaire scores</measure>
    <time_frame>6 weeks, 8 weeks, 12 weeks, 6 months</time_frame>
    <description>GSRS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in hospital and anxiety depression scores</measure>
    <time_frame>6 weeks, 8 weeks, 12 weeks, 6 months</time_frame>
    <description>HADS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in number and form of bowel movements</measure>
    <time_frame>6 weeks, 8 weeks, 12 weeks, 6 months</time_frame>
    <description>1-week-diaries</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in faecal and mucosal microbiota composition</measure>
    <time_frame>faecal: 6 weeks, 8 weeks, 12 weeks, 6 months; mucosal: 6 weeks</time_frame>
    <description>16S rRNA-based next generation sequencing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in lymphocyte infiltration</measure>
    <time_frame>6 weeks</time_frame>
    <description>Immunohistochemistry and flow cytometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in subepithelial collagen layer</measure>
    <time_frame>6 weeks</time_frame>
    <description>Immunohistochemistry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in immune cell composition of colonic biopsies</measure>
    <time_frame>6 weeks</time_frame>
    <description>Immunohistochemistry and flow cytometry</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Changes in inflammation markers in faecal samples such as faecal calprotectin</measure>
    <time_frame>6 weeks, 8 weeks, 12 weeks, 6 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Changes in metabolite profile in faecal samples and blood</measure>
    <time_frame>faecal: 6 weeks, 8 weeks, 12 weeks, 6 months; blood: 6 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Changes in gene expression in mucosal biopsies</measure>
    <time_frame>6 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Changes in barrier function markers in colonic biopsies</measure>
    <time_frame>6 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Changes in gene expression of butyrate transporters in colonic biopsies</measure>
    <time_frame>6 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Changes in markers of inflammation and intestinal barrier function in blood</measure>
    <time_frame>6 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Changes in plasma levels of cardiovascular disease markers and platelet responsiveness and aggregation</measure>
    <time_frame>6 weeks</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Microscopic Colitis</condition>
  <arm_group>
    <arm_group_label>Faecal microbiota transfer (FMT)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Suspended stool from a healthy donor</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Faecal microbiota transfer (FMT)</intervention_name>
    <description>Suspended stool from a healthy donor</description>
    <arm_group_label>Faecal microbiota transfer (FMT)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria for patients:&#xD;
&#xD;
          1. Signed informed consent&#xD;
&#xD;
          2. Active MC diagnosis, defined as &gt;3 stools a day from which at least one should be&#xD;
             watery&#xD;
&#xD;
          3. Willingness to stop budesonide treatment during participation in the trial&#xD;
&#xD;
          4. Age: 18-70 years&#xD;
&#xD;
        Exclusion criteria for patients&#xD;
&#xD;
          1. Previous complicated gastrointestinal surgery&#xD;
&#xD;
          2. Malignant disease except non-melanoma skin cancer&#xD;
&#xD;
          3. Dementia, severe depression, major psychiatric disorder, or other incapacity for&#xD;
             adequate cooperation&#xD;
&#xD;
          4. C. difficile or other current gastroenteritis&#xD;
&#xD;
          5. Females who are pregnant or breast-feeding&#xD;
&#xD;
          6. Severe endometriosis&#xD;
&#xD;
          7. Antimicrobial treatment 4 weeks prior to first screening visit&#xD;
&#xD;
          8. Antimicrobial prophylaxis (eg. acne, urinary tract infection)&#xD;
&#xD;
          9. Regular consumption of probiotic products 4 weeks prior to randomization&#xD;
&#xD;
         10. Recently diagnosed lactose intolerance (less than 6 months prior to first screening&#xD;
             visit)&#xD;
&#xD;
         11. Recently diagnosed coeliac disease (less than 6 months prior to first screening visit)&#xD;
&#xD;
         12. Regular intake of NSAIDs (non steroidal anti-inflammatory drugs)&#xD;
&#xD;
         13. Abuse of alcohol or drugs&#xD;
&#xD;
         14. Any clinically significant disease/condition which in the investigator's opinion could&#xD;
             interfere with the results of the trial&#xD;
&#xD;
        Inclusion criteria for donors&#xD;
&#xD;
          1. Signed informed consent&#xD;
&#xD;
          2. High-butyrate producing microbiota in faecal samples&#xD;
&#xD;
          3. Age: 18-65 years&#xD;
&#xD;
        Exclusion criteria for donors&#xD;
&#xD;
          1. Known organic gastrointestinal disease (e.g. IBD, IBS, chronic diarrhoea or&#xD;
             constipation)&#xD;
&#xD;
          2. First degree relative with IBD&#xD;
&#xD;
          3. History of or present gastrointestinal malignancy or polyposis&#xD;
&#xD;
          4. Recent (gastrointestinal) infection (within last 6 months)&#xD;
&#xD;
          5. History of major gastrointestinal surgery (e.g. gastric bypass)&#xD;
&#xD;
          6. Eosinophilic disorders of the gastrointestinal tract&#xD;
&#xD;
          7. Current communicable disease (e.g. upper respiratory tract infection)&#xD;
&#xD;
          8. Malignant disease and/or patients who are receiving systemic anti-neoplastic agents&#xD;
&#xD;
          9. Psychiatric diseases (e.g. dementia, depression, schizophrenia, autism, Asperger&#xD;
             Syndrome) or other incapacity for adequate cooperation&#xD;
&#xD;
         10. Chronic neurological/neurodegenerative diseases (e.g. Parkinson's disease, multiple&#xD;
             sclerosis)&#xD;
&#xD;
         11. Autoimmune disease and/or patients receiving immunosuppressive medications&#xD;
&#xD;
         12. Major relevant allergies (e.g. food allergy, multiple allergies)&#xD;
&#xD;
         13. Chronic pain syndromes (e.g. fibromyalgia)&#xD;
&#xD;
         14. Chronic fatigue syndrome&#xD;
&#xD;
         15. HIV, hepatitis A, B, C or known exposure within the recent 12 months&#xD;
&#xD;
         16. Obesity (BMI&gt;30) or metabolic syndrome&#xD;
&#xD;
         17. Antimicrobial treatment or prophylaxis within the last 3 months&#xD;
&#xD;
         18. Other chronic use of drugs that may affect the microbiome, e.g. proton pump inhibitors&#xD;
&#xD;
         19. First degree relative with cardiovascular thrombosis before 50 years of age&#xD;
&#xD;
         20. Females who are pregnant or breast-feeding&#xD;
&#xD;
         21. Known clinically significant abnormal laboratory values&#xD;
&#xD;
         22. Participation in high-risk sexual behaviours&#xD;
&#xD;
         23. Abuse of alcohol or drugs&#xD;
&#xD;
         24. Tattoo or body piercing within the last 6 months&#xD;
&#xD;
         25. Travelling in countries with low hygiene or high infection risk for endemic diarrhoea&#xD;
             within the last 6 months&#xD;
&#xD;
         26. Positive stool testing for C. difficile, ova and parasites (e.g. Cyclospora, Isospora,&#xD;
             Cryptosporidium), enteric pathogens (e.g. enterohaemorrhagic E. coli, Salmonella,&#xD;
             Shigella, Yersinia, Campylobacter, Giarda antigen, amoebas)&#xD;
&#xD;
         27. Positive stool testing for multiresistant bacteria (e.g. extended-spectrum beta-&#xD;
             lactamase (ESBL) producing organisms, multi-resistant Gram-negative bacilli (MRGN) 3&#xD;
             and 4, vancomycin-resistant enterococci (VRE) or methicillin-resistant Staphylococcus&#xD;
             aureus (MRSA))&#xD;
&#xD;
         28. Calprotectin &gt; 50 μg/g of faeces&#xD;
&#xD;
         29. Positive blood testing for HIV, Hepatitis A, B, C, syphilis, Human T-lymphotropic&#xD;
             virus (HTLV), cytomegalovirus (CMV) and Epstein Barr Virus (EBV)&#xD;
&#xD;
         30. Any clinically significant disease/condition which in the investigator's opinion could&#xD;
             interfere with the results of the trial&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Robert J Brummer, Professor, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Örebro University, Sweden</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Örebro</name>
      <address>
        <city>Örebro</city>
        <state>Örebro County</state>
        <zip>70185</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>August 28, 2017</study_first_submitted>
  <study_first_submitted_qc>September 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 7, 2017</study_first_posted>
  <last_update_submitted>February 20, 2020</last_update_submitted>
  <last_update_submitted_qc>February 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 21, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Örebro University, Sweden</investigator_affiliation>
    <investigator_full_name>Robert Brummer</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>Colitis</mesh_term>
    <mesh_term>Colitis, Microscopic</mesh_term>
  </condition_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/NCT03275467
org study id: 2017/072
nct id: NCT03275467
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Microscopic colitis (MC) is a disease with chronic inflammation of the colon that is mostly
      diagnosed in middle-aged or elderly women. Patients suffer from chronic watery diarrhoea,
      abdominal pain and weight loss. The aetiology of MC is still unknown but it is hypothesized
      that MC is caused by a deregulated immune response to a luminal agent in predisposed
      individuals, and an important role of the intestinal microbiota is suggested.

      In the current proof-of-concept study, the effect of faecal microbiota transfer (FMT) in 10
      MC patients will be evaluated. FMT consists in the infusion of suspended stool from a healthy
      donor into the intestine of a patient with the aim to restore a disturbed intestinal
      microbiota.
This will be an intervention pilot study with a 12-week and an optional 6-months follow-up
      period. It will be investigated if the infusion of suspended stool from healthy donors
      improves the symptoms of MC patients by restoring their disturbed intestinal microbiota. This
      procedure is known as faecal microbiota transplantation (FMT).

      MC patients (n=10) will be randomised to receive FMT using stool from one of two healthy
      donors.

      At baseline, blood samples and mucosal biopsies will be obtained from the descending colon.
      In addition, faecal samples will be collected and patients will complete symptom
      questionnaires. The first FMT will be administered by colonoscopy, FMT 2-3 by enemas. Faecal
      samples will be collected and questionnaires will be completed at different time points
      during the study. The patients will be followed-up at 6 weeks, 8 weeks, 12 weeks and 6 months
      after receiving FMT 1, however, the follow-up after 6 months will be optional. Additional
      biopsies from the descending colon and blood samples will be collected 6 weeks after the
      first FMT.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of MC patients in remission six weeks after the first FMT.
time frame: 6 weeks
description: Remission is defined as <3 stools per day and a mean of less than one watery stool per day.
measure: Changes in general health and symptom questionnaire scores
time frame: 6 weeks, 8 weeks, 12 weeks, 6 months
description: SHS
measure: Changes in general health questionnaire scores
time frame: 6 weeks, 8 weeks, 12 weeks, 6 months
description: SF-36
measure: Changes in quality of life questionnaire scores
time frame: 6 weeks, 8 weeks, 12 weeks, 6 months
description: EG-5D-5L
measure: Changes in gastrointestinal symptom questionnaire scores
time frame: 6 weeks, 8 weeks, 12 weeks, 6 months
description: GSRS
measure: Changes in hospital and anxiety depression scores
time frame: 6 weeks, 8 weeks, 12 weeks, 6 months
description: HADS
measure: Changes in number and form of bowel movements
time frame: 6 weeks, 8 weeks, 12 weeks, 6 months
description: 1-week-diaries
measure: Changes in faecal and mucosal microbiota composition
time frame: faecal: 6 weeks, 8 weeks, 12 weeks, 6 months; mucosal: 6 weeks
description: 16S rRNA-based next generation sequencing
measure: Changes in lymphocyte infiltration
time frame: 6 weeks
description: Immunohistochemistry and flow cytometry
measure: Changes in subepithelial collagen layer
time frame: 6 weeks
description: Immunohistochemistry
measure: Changes in immune cell composition of colonic biopsies
time frame: 6 weeks
description: Immunohistochemistry and flow cytometry
measure: Changes in inflammation markers in faecal samples such as faecal calprotectin
time frame: 6 weeks, 8 weeks, 12 weeks, 6 months
measure: Changes in metabolite profile in faecal samples and blood
time frame: faecal: 6 weeks, 8 weeks, 12 weeks, 6 months; blood: 6 weeks
measure: Changes in gene expression in mucosal biopsies
time frame: 6 weeks
measure: Changes in barrier function markers in colonic biopsies
time frame: 6 weeks
measure: Changes in gene expression of butyrate transporters in colonic biopsies
time frame: 6 weeks
measure: Changes in markers of inflammation and intestinal barrier function in blood
time frame: 6 weeks
measure: Changes in plasma levels of cardiovascular disease markers and platelet responsiveness and aggregation
time frame: 6 weeks
arm group label: Faecal microbiota transfer (FMT)
arm group type: Experimental
description: Suspended stool from a healthy donor
intervention type: Other
intervention name: Faecal microbiota transfer (FMT)
description: Suspended stool from a healthy donor
arm group label: Faecal microbiota transfer (FMT)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Robert J Brummer, Professor, MD
role: Principal Investigator
affiliation: Örebro University, Sweden
facility: 
country: Sweden
responsible party type: Principal Investigator
investigator affiliation: Örebro University, Sweden
investigator full name: Robert Brummer
investigator title: Professor
mesh term: Colitis
mesh term: Colitis, Microscopic
sharing ipd: No