<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/NCT03822299</url>
  </required_header>
  <id_info>
    <org_study_id>HelseFonna</org_study_id>
    <nct_id>NCT03822299</nct_id>
  </id_info>
  <brief_title>Effects of Faecal Microbiota Transplantation in Patients With IBS</brief_title>
  <official_title>Effects of Faecal Microbiota Transplantation in Patients With Irritable Bowel Syndrome: A Randomised, Double-blind Placebo-controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Helse Fonna</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Helse Vest</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Helse Fonna</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Irritable bowel syndrom (IBS) is a common chronic gastrointestinal disorder that affects&#xD;
      10-20% of the world population. The prevalence of IBS in Norway is between 8% and 25%. The&#xD;
      pathophysiology of IBS is incompletely understood, and there is no effective treatment for&#xD;
      this condition. Imbalance (dysbiosis) of the gut microbiome has been found in patients with&#xD;
      IBS. In the absence of effective method to restore the dysbiosis, transplantation of a&#xD;
      microbiome from healthy individuals with well-functioning gut (FMT) to those with IBS has&#xD;
      been performed. Two randomized double blind placebo-controlled (RCT) studies have been&#xD;
      published recently. Whereas it was reported in one study that FMT reduced symptom and&#xD;
      improved quality of life in patients with IBS, FMT had no effect in the other study. In order&#xD;
      to clarify these contradictory results, a new RCT study that enrolled larger number of&#xD;
      patients is required. In this study, the investigators intend to recruit 170 IBS patients&#xD;
      from those attending outdoor clinic at Stord hospital in a randomized, double blind placebo&#xD;
      trial. A single healthy donor with well-characterized microbiome is going to be used. The&#xD;
      effects on symptoms, quality of life, fatigue as well as dysbiosis before and after FMT are&#xD;
      going to be investigated. The possible mechanisms behind the effects if any of FMT such as&#xD;
      changes in intestinal stem cells, enteroendocrine cells and local immune defense shall be&#xD;
      also investigated. The patients are going to be randomized either to placebo (own faces), 30&#xD;
      g or 60 g of the donor faces in ratio 1:1:1.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study design Patients One hundred and seventy patients who fulfill the following inclusion&#xD;
      criteria and lack the exclusion criteria shall be included. In addition, the patients are&#xD;
      examined physically, and blood tests are taken to exclude inflammation, and liver, kidney and&#xD;
      thyroid diseases. They undergo further gastroscopy with duodenal biopsies to exclude coeliac&#xD;
      disease. They undergo also colonoscopy to exclude malignity, or inflammatory bowel disease&#xD;
      (IBD). Microscopic colitis is excluded by examining tissue obtained by colonoscopy with&#xD;
      segmental biopsy sampling.&#xD;
&#xD;
      Donor selection and screening:&#xD;
&#xD;
      A single donor shall be selected and screened according to the European and international&#xD;
      guidelines. The donor should not be a first-degree relative to any of the patients, as the&#xD;
      intestinal microbiota is affected by the genetic composition, and similarity between the&#xD;
      donor and recipient in the fecal microbiota may occur.&#xD;
&#xD;
      Protocol&#xD;
&#xD;
      Feces collection, preparation and administration:&#xD;
&#xD;
      Feces from both the donors and recipients were collected and stored at - 80•. Frozen feces&#xD;
      (30 or 60g) from the donor or patients (placebo), thawed at 5° C and were dissolved in 50 mL&#xD;
      of 0.9% sterile saline per 30 g feces. The dissolved stool is administrated to the patients,&#xD;
      after overnight fast, through working channel of gastroduodeno-scope in pars descendent&#xD;
      duodenum distal to the papilla of Vater.&#xD;
&#xD;
      Sigmoidoscopy: After administration of faeces, a sigmoidoscopy is performed during which 4&#xD;
      biopsies from the sigmoid colon about 30 cm from anus, and 4 biopsies from the rectum about&#xD;
      15 cm from anus are taken. Sigmoidoscopy is repeated in the same way 1 month after FMT.&#xD;
&#xD;
      Methods Questionnaires&#xD;
&#xD;
        1. IBS symptom severity Scale (IBS-SSS) questionnaire.&#xD;
&#xD;
        2. Birmingham Symptom scale questionnaires.&#xD;
&#xD;
        3. IBSQoL questionnaire.&#xD;
&#xD;
        4. Short form of Nepean Dyspepsia Index (SF-NDI) questionnaire.&#xD;
&#xD;
        5. Fatigue Assessment Scale (FAS).&#xD;
&#xD;
      Microbiome analysis Gut microbiota analysis was performed using the GA-mapTM Dysbiosis test&#xD;
      (Genetic Analysis AS, Oslo, Norway) by algorithmically assessing fecal bacterial abundance&#xD;
      and profile (dysbiosis index, DI), and potential deviation in the microbiome from&#xD;
      normobiosis. GA-map test is based on fecal homogenization, mechanical bacterial cell&#xD;
      disruption and automated total bacterial genomic DNA extraction using magnetic beads. DI is&#xD;
      based on 54 DNA probes targeting more than 300 bacterial strains based on their 16S rRNA&#xD;
      sequence in seven variable regions (V3-V9). Twenty-six bacteria probes are species specific,&#xD;
      19 detect bacteria on genus level, and 9 probes detect bacteria at higher taxonomic levels.&#xD;
      Probe labeling is by single nucleotide extension and hybridization to complementary probes&#xD;
      coupled to magnetic beads, and signal detection by using Bio Code 1000A 128-Plex Analyzer&#xD;
      (Applied Bio Code, Santa Fe Springs, CA, USA). A DI above 2 shows a microbiota profile that&#xD;
      differs from that of the normobiotic reference collection (DI 1-2: non-dysbiosis, DI:&#xD;
      moderate, DI 4-5: severe dysbiosis).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2018</start_date>
  <completion_date type="Actual">May 5, 2019</completion_date>
  <primary_completion_date type="Actual">April 30, 2019</primary_completion_date>
  <phase>N/A</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>Intervention. Dietary supplement: fecal suspension. Healthy donor or own faeces (placebo) administrated through working canal of a gastroscope.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>A research nurse, not involved in the trial, create the allocation sequence using a website. This was done in blocks of 21 patients.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Global improvement in IBS symptoms as assessed by IBS Symptom Severity Scale (IBS-SSS)</measure>
    <time_frame>3 months.</time_frame>
    <description>IBS-SSS is a visual assessment scale (VAS) rating from 0 to 100, with total scores ranging from 0 to 500. Lower scores indicate improvement.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Global improvement in IBS symptoms as assessed by Birmingham Symptom scale questionnaire</measure>
    <time_frame>3 months.</time_frame>
    <description>This questionnaire consists of 11 question. measured on a six-point Likert scale ranging from 0 to 5. Lower scores indicate improvement.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Quality of life as assessed by IBS quality of life (IBSQoL) questionnaire</measure>
    <time_frame>3 months</time_frame>
    <description>IBSQoL consist of 34- questions measured on a five-point Likert scale ranging from 0 to 5. Higher scores indicate improvement.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Quality of life as assessed by Short form of Nepean Dyspepsia Index (SF-NDI) questionnaires</measure>
    <time_frame>3 months</time_frame>
    <description>SF-NDI is a five-point Likert scale ranging from 0 to 5. Lower scores indicate improvement.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Fatigue as assessed by: Fatigue Assessment Scale (FAS) questionnaire</measure>
    <time_frame>3 months</time_frame>
    <description>FAS is a five-point Likert scale ranging from 0 to 5. Lower scores indicate improvement.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Stool microbiota changes as assessed by the Dysbiosis index (DI)</measure>
    <time_frame>3 months.</time_frame>
    <description>DI is a 5-point scale: DI 1-2: non-dysbiosis, DI: moderate, DI 4-5: severe dysbiosis). Higer scores indicate improvement.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Adverse events</measure>
    <time_frame>up to the end point (3 months)</time_frame>
    <description>Patients are encouraged to keep a diary of any adverse events such as diarrhea, constipation, abdominal pain/ if any.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">164</enrollment>
  <condition>Irritable Bowel Syndrome</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients receive suspension of their own feces.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>30 g donor dose</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receiving 30 g of a healthy donor feces.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>60 g donor dose</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receiving 60 g of a healthy donor feces.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>healthy feces microbiota</intervention_name>
    <description>Suspension of healthy feces microbiota in sterile saline solution</description>
    <arm_group_label>30 g donor dose</arm_group_label>
    <arm_group_label>60 g donor dose</arm_group_label>
    <other_name>placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. Patients between who fulfill Rome IV criteria for the diagnosis of IBS.&#xD;
&#xD;
          2. Patients with moderate to severe IBS symptoms (IBS-SSS ≥ 175).&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Pregnant, planning pregnancy or lactating women.&#xD;
&#xD;
          2. The use of antibiotics or probiotics within 1 month prior to FMT.&#xD;
&#xD;
          3. Patients who had undergone any abdominal surgery, with the exception of appendectomy,&#xD;
             cholecystectomy, Caesarean section or hysterectomy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Haldis Lier, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Head of Research Department at Helse Finna HF</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Helse Fonna</name>
      <address>
        <city>Haugesund</city>
        <zip>5504</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Norway</country>
  </location_countries>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>December 21, 2018</study_first_submitted>
  <study_first_submitted_qc>January 27, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <last_update_submitted>May 5, 2019</last_update_submitted>
  <last_update_submitted_qc>May 5, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 7, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Helse Fonna</investigator_affiliation>
    <investigator_full_name>Magdy El-Salhy, MD, PhD</investigator_full_name>
    <investigator_title>Professor/Consultant gatroenterologist</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Irritable Bowel Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>All data are stored at Helse Vest server. Anonymous patients data is available to other research on demand.</ipd_description>
  </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/NCT03822299
org study id: HelseFonna
nct id: NCT03822299
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Irritable bowel syndrom (IBS) is a common chronic gastrointestinal disorder that affects
      10-20% of the world population. The prevalence of IBS in Norway is between 8% and 25%. The
      pathophysiology of IBS is incompletely understood, and there is no effective treatment for
      this condition. Imbalance (dysbiosis) of the gut microbiome has been found in patients with
      IBS. In the absence of effective method to restore the dysbiosis, transplantation of a
      microbiome from healthy individuals with well-functioning gut (FMT) to those with IBS has
      been performed. Two randomized double blind placebo-controlled (RCT) studies have been
      published recently. Whereas it was reported in one study that FMT reduced symptom and
      improved quality of life in patients with IBS, FMT had no effect in the other study. In order
      to clarify these contradictory results, a new RCT study that enrolled larger number of
      patients is required. In this study, the investigators intend to recruit 170 IBS patients
      from those attending outdoor clinic at Stord hospital in a randomized, double blind placebo
      trial. A single healthy donor with well-characterized microbiome is going to be used. The
      effects on symptoms, quality of life, fatigue as well as dysbiosis before and after FMT are
      going to be investigated. The possible mechanisms behind the effects if any of FMT such as
      changes in intestinal stem cells, enteroendocrine cells and local immune defense shall be
      also investigated. The patients are going to be randomized either to placebo (own faces), 30
      g or 60 g of the donor faces in ratio 1:1:1.
Study design Patients One hundred and seventy patients who fulfill the following inclusion
      criteria and lack the exclusion criteria shall be included. In addition, the patients are
      examined physically, and blood tests are taken to exclude inflammation, and liver, kidney and
      thyroid diseases. They undergo further gastroscopy with duodenal biopsies to exclude coeliac
      disease. They undergo also colonoscopy to exclude malignity, or inflammatory bowel disease
      (IBD). Microscopic colitis is excluded by examining tissue obtained by colonoscopy with
      segmental biopsy sampling.

      Donor selection and screening:

      A single donor shall be selected and screened according to the European and international
      guidelines. The donor should not be a first-degree relative to any of the patients, as the
      intestinal microbiota is affected by the genetic composition, and similarity between the
      donor and recipient in the fecal microbiota may occur.

      Protocol

      Feces collection, preparation and administration:

      Feces from both the donors and recipients were collected and stored at - 80•. Frozen feces
      (30 or 60g) from the donor or patients (placebo), thawed at 5° C and were dissolved in 50 mL
      of 0.9% sterile saline per 30 g feces. The dissolved stool is administrated to the patients,
      after overnight fast, through working channel of gastroduodeno-scope in pars descendent
      duodenum distal to the papilla of Vater.

      Sigmoidoscopy: After administration of faeces, a sigmoidoscopy is performed during which 4
      biopsies from the sigmoid colon about 30 cm from anus, and 4 biopsies from the rectum about
      15 cm from anus are taken. Sigmoidoscopy is repeated in the same way 1 month after FMT.

      Methods Questionnaires

        1. IBS symptom severity Scale (IBS-SSS) questionnaire.

        2. Birmingham Symptom scale questionnaires.

        3. IBSQoL questionnaire.

        4. Short form of Nepean Dyspepsia Index (SF-NDI) questionnaire.

        5. Fatigue Assessment Scale (FAS).

      Microbiome analysis Gut microbiota analysis was performed using the GA-mapTM Dysbiosis test
      (Genetic Analysis AS, Oslo, Norway) by algorithmically assessing fecal bacterial abundance
      and profile (dysbiosis index, DI), and potential deviation in the microbiome from
      normobiosis. GA-map test is based on fecal homogenization, mechanical bacterial cell
      disruption and automated total bacterial genomic DNA extraction using magnetic beads. DI is
      based on 54 DNA probes targeting more than 300 bacterial strains based on their 16S rRNA
      sequence in seven variable regions (V3-V9). Twenty-six bacteria probes are species specific,
      19 detect bacteria on genus level, and 9 probes detect bacteria at higher taxonomic levels.
      Probe labeling is by single nucleotide extension and hybridization to complementary probes
      coupled to magnetic beads, and signal detection by using Bio Code 1000A 128-Plex Analyzer
      (Applied Bio Code, Santa Fe Springs, CA, USA). A DI above 2 shows a microbiota profile that
      differs from that of the normobiotic reference collection (DI 1-2: non-dysbiosis, DI:
      moderate, DI 4-5: severe dysbiosis).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Intervention. Dietary supplement: fecal suspension. Healthy donor or own faeces (placebo) administrated through working canal of a gastroscope.
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: A research nurse, not involved in the trial, create the allocation sequence using a website. This was done in blocks of 21 patients.
measure: Global improvement in IBS symptoms as assessed by IBS Symptom Severity Scale (IBS-SSS)
time frame: 3 months.
description: IBS-SSS is a visual assessment scale (VAS) rating from 0 to 100, with total scores ranging from 0 to 500. Lower scores indicate improvement.
measure: Global improvement in IBS symptoms as assessed by Birmingham Symptom scale questionnaire
time frame: 3 months.
description: This questionnaire consists of 11 question. measured on a six-point Likert scale ranging from 0 to 5. Lower scores indicate improvement.
measure: Quality of life as assessed by IBS quality of life (IBSQoL) questionnaire
time frame: 3 months
description: IBSQoL consist of 34- questions measured on a five-point Likert scale ranging from 0 to 5. Higher scores indicate improvement.
measure: Quality of life as assessed by Short form of Nepean Dyspepsia Index (SF-NDI) questionnaires
time frame: 3 months
description: SF-NDI is a five-point Likert scale ranging from 0 to 5. Lower scores indicate improvement.
measure: Fatigue as assessed by: Fatigue Assessment Scale (FAS) questionnaire
time frame: 3 months
description: FAS is a five-point Likert scale ranging from 0 to 5. Lower scores indicate improvement.
measure: Stool microbiota changes as assessed by the Dysbiosis index (DI)
time frame: 3 months.
description: DI is a 5-point scale: DI 1-2: non-dysbiosis, DI: moderate, DI 4-5: severe dysbiosis). Higer scores indicate improvement.
measure: Adverse events
time frame: up to the end point (3 months)
description: Patients are encouraged to keep a diary of any adverse events such as diarrhea, constipation, abdominal pain/ if any.
arm group label: Placebo
arm group type: No Intervention
description: Patients receive suspension of their own feces.
arm group label: 30 g donor dose
arm group type: Active Comparator
description: Patients receiving 30 g of a healthy donor feces.
arm group label: 60 g donor dose
arm group type: Active Comparator
description: Patients receiving 60 g of a healthy donor feces.
intervention type: Dietary Supplement
intervention name: healthy feces microbiota
description: Suspension of healthy feces microbiota in sterile saline solution
arm group label: 30 g donor dose
arm group label: 60 g donor dose
other name: placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Haldis Lier, MD, PhD
role: Study Director
affiliation: Head of Research Department at Helse Finna HF
facility: 
country: Norway
responsible party type: Principal Investigator
investigator affiliation: Helse Fonna
investigator full name: Magdy El-Salhy, MD, PhD
investigator title: Professor/Consultant gatroenterologist
mesh term: Irritable Bowel Syndrome
mesh term: Syndrome
sharing ipd: No
ipd description: All data are stored at Helse Vest server. Anonymous patients data is available to other research on demand.