<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/NCT02259465</url>
  </required_header>
  <id_info>
    <org_study_id>SoM A14082014 FOG</org_study_id>
    <nct_id>NCT02259465</nct_id>
  </id_info>
  <brief_title>The Effect of the Low FODMAP Diet and Dietary Oligofructose on Gastrointestinal Form, Function and Microbiota</brief_title>
  <acronym>FOG</acronym>
  <official_title>A Randomised Controlled Trial of the Effect of the Low FODMAP Diet and Dietary Oligofructose on Gastrointestinal Form, Function and Microbiota in Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Nottingham</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>King's College London</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Nottingham</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Some carbohydrates, complex sugars, which are found in grains, fruit and vegetables, cannot&#xD;
      be digested by humans. When eaten they pass through the small bowel to the large bowel, or&#xD;
      colon. Some bacteria that live in the colon are able to digest these carbohydrates, and use&#xD;
      them as an energy source. This releases energy that humans can absorb, and may have other&#xD;
      effects on health as well. The process also releases gases such as hydrogen and methane into&#xD;
      the colon, which will eventually be released as flatulence.&#xD;
&#xD;
      There is some evidence in animals, and humans, that changing the carbohydrate content of the&#xD;
      diet may increase the numbers of bacteria in the colon that can use this energy source.&#xD;
      Recent work has looked at how changes in colon bacteria and carbohydrate in the diet affect&#xD;
      transit, the speed at which food and stool moves through the stomach and bowels.&#xD;
&#xD;
      This undergraduate project will use techniques in Magnetic Resonance Imaging developed in&#xD;
      Nottingham to investigate how a prolonged change in dietary carbohydrate might affect speed&#xD;
      of transit through the bowel and gas production in the colon, and whether there is any immune&#xD;
      reaction to the carbohydrate from the bowel wall.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Oligofructose (OF) is a fructose- based oligosaccharide and defined in the European Union as&#xD;
      a dietary fibre. Enzymatically derived from the longer chain inulin in chicory, it is&#xD;
      commonly used in processed food to improve mouth feel in fat-free products. OF is poorly&#xD;
      digested and absorbed in the small bowel so passes to the colon where it is fermented by the&#xD;
      bacteria usually resident in the colon, termed the microbiota. This process produces gases&#xD;
      such as hydrogen and sometimes methane, and short-chain fatty acids (SCFAs) which have a&#xD;
      variety of roles including nutrition to colonocytes, immunological effects and modulation of&#xD;
      intestinal motility. Its presence in the colon alters the composition of the microbiota, with&#xD;
      reported potential benefits to health, leading to its description as a 'prebiotic'.&#xD;
&#xD;
      Recently, however, such poorly digested carbohydrates grouped together by the term FODMAP&#xD;
      (fermentable oligo-, di-, mono-saccharides and polyols) have been proposed to exacerbate&#xD;
      symptoms of irritable bowel syndrome (IBS) such as abdominal discomfort and bloating. Dietary&#xD;
      exclusion of foods containing FODMAPs, such as wheat, dairy and certain fruit and vegetables,&#xD;
      has been proposed as a treatment for IBS, with some evidence to support this. FODMAPs are&#xD;
      thought to induce symptoms either by drawing water into the small bowel by osmosis, or&#xD;
      through gaseous distension of the large bowel or a combination of these along with metabolite&#xD;
      effects on motility.&#xD;
&#xD;
      The Nottingham GI MRI group has been at the forefront of elucidating the actual effects of&#xD;
      FODMAPs on gastrointestinal (GI) physiology. We have published techniques to measure small&#xD;
      bowel water content, colonic volume and gas volume and whole gut transit time. We have&#xD;
      recently demonstrated that a single, large (40g) dose of inulin leads to an increase in&#xD;
      colonic volume, mainly through an increase in colonic gas. Such a dose is beyond the usual&#xD;
      range of dietary variation, however. Last year we piloted a model more similar to dietary&#xD;
      practice. Participants supplemented their usual diet with 5g OF twice daily for a week. The&#xD;
      most striking result was an 18% increase in fasting colonic volume. This could not be&#xD;
      explained by changes in colonic gas and may represent proliferation, and increased mass, of&#xD;
      the microbiota. That study was an open label, uncontrolled case series so we now wish to test&#xD;
      the hypothesis in a double-blind, randomised controlled trial. For explanatory purposes we&#xD;
      will also measure whole gut transit, colonic gas volume and hydrogen and methane expired in&#xD;
      the breath. For exploratory purposes we will also collect stool and urine samples to allow&#xD;
      assessment of the effect on microbiota and their metabolic output.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">December 2014</completion_date>
  <primary_completion_date type="Actual">December 2014</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>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in colonic volume</measure>
    <time_frame>one week</time_frame>
    <description>Percentage change from baseline in fasting colonic volume after one week of intervention, as measured by Magnetic Resonance Imaging (MRI)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in whole gut transit time</measure>
    <time_frame>one week</time_frame>
    <description>Change in whole gut transit time (WGTT) after one week of intervention, as determined by Weighted Average Position Score (WAPS) of MRI transit markers 24 hours after ingestion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in colonic gas volume</measure>
    <time_frame>one week</time_frame>
    <description>Percentage change in fasting colonic gas volume after one week of intervention, as measured by MRI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in fasting breath hydrogen</measure>
    <time_frame>one week</time_frame>
    <description>Change in fasting breath hydrogen concentration after one week of intervention, measured in parts per million</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in fasting breath methane</measure>
    <time_frame>one week</time_frame>
    <description>Change in fasting breath methane concentration after one week of intervention, measured in parts per million</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in urinary metabolites</measure>
    <time_frame>one week</time_frame>
    <description>Exploratory work to assess change in urinary metabolite concentrations after one week of intervention</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in faecal microbiota</measure>
    <time_frame>one week</time_frame>
    <description>Exploratory work to assess change in faecal microbiota concentrations after one week of intervention</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in faecal short-chain fatty acids</measure>
    <time_frame>one week</time_frame>
    <description>Exploratory work to assess change in faecal short-chain fatty acid concentrations after one week of intervention</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Irritable Bowel Syndrome</condition>
  <arm_group>
    <arm_group_label>Oligofructose</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will be asked to follow the low FODMAP diet for a week, supplementing the diet with oligofructose, 7grams twice daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Maltodextrin</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will be asked to follow the low FODMAP diet for a week, supplementing the diet with maltodextrin, 7grams twice daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>low FODMAP diet</intervention_name>
    <description>Participants will attend a one-hour group session on how to follow the low FODMAP diet, run by a dietitian trained in the diet. They will be asked to follow the diet for 7 days while keeping a food diary.</description>
    <arm_group_label>Maltodextrin</arm_group_label>
    <arm_group_label>Oligofructose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Oligofructose</intervention_name>
    <description>Participants will supplement their diet with 7 grams of OF twice daily for the week that they follow the low FODMAP diet.</description>
    <arm_group_label>Oligofructose</arm_group_label>
    <other_name>OraftiP95, OF</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Maltodextrin</intervention_name>
    <description>Participants will supplement their diet with 7 grams of maltodextrin twice daily for the week that they follow the low FODMAP diet.</description>
    <arm_group_label>Maltodextrin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Aged 18 or older&#xD;
&#xD;
          -  Able to give informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Self-declared vegetarian, vegan or kosher/ halal diet who cannot eat carmine red dye&#xD;
&#xD;
          -  Pregnancy declared by candidate&#xD;
&#xD;
          -  History declared by the candidate of pre-existing gastrointestinal disorder that may&#xD;
             affect bowel function&#xD;
&#xD;
          -  A positive diagnosis of irritable bowel syndrome based on the Rome III criteria&#xD;
             questionnaire&#xD;
&#xD;
          -  Reported history of previous resection of the oesophagus, stomach or intestine&#xD;
             (excluding appendix)&#xD;
&#xD;
          -  Intestinal stoma&#xD;
&#xD;
          -  Any medical condition making participation potentially compromising participation in&#xD;
             the study e.g. diabetes mellitus, respiratory disease limiting ability to lie in the&#xD;
             scanner&#xD;
&#xD;
          -  Contraindications for MRI scanning i.e. metallic implants, pacemakers, history of&#xD;
             metallic foreign body in eye(s) and penetrating eye injury&#xD;
&#xD;
          -  Will not limit alcohol intake to ≤ 35 units/ week and ≤ 8 units per day during trial&#xD;
&#xD;
          -  Unable to stop drugs known to alter GI motility including mebeverine, opiates,&#xD;
             monoamine oxidase inhibitors, phenothiazines, benzodiazepines, calcium channel&#xD;
             antagonists for the duration of the study (Selective serotonin reuptake inhibitors and&#xD;
             low dose tricyclic antidepressants will be recorded but will not be an exclusion&#xD;
             criteria)&#xD;
&#xD;
          -  Antibiotic or prescribed probiotic treatment in the past 8 weeks&#xD;
&#xD;
          -  Inability to lie flat or exceed scanner limits of weight &lt;120kg&#xD;
&#xD;
          -  Poor understanding of English language&#xD;
&#xD;
          -  Participation in night shift work the week prior to the study day. Night work is&#xD;
             defined as working between midnight and 6.00 AM&#xD;
&#xD;
          -  Participation in any medical trials for the past 3 months&#xD;
&#xD;
          -  Anyone who in the opinion of the investigator is unlikely to be able to comply with&#xD;
             the protocol e.g. cognitive dysfunction, chaotic lifestyle related to substance abuse&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Robin C Spiller, MD FRCP</last_name>
    <role>Study Chair</role>
    <affiliation>University of Nottingham</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Giles AD Major, BMBCh MRCP</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Nottingham</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nottingham Digestive Diseases Centre</name>
      <address>
        <city>Nottingham</city>
        <zip>NG7 2UH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <link>
    <url>http://www.nddcbru.org.uk</url>
    <description>Related Info</description>
  </link>
  <link>
    <url>https://www.facebook.com/UoN.Gastrointestinal.MRI</url>
    <description>Related Info</description>
  </link>
  <verification_date>March 2015</verification_date>
  <study_first_submitted>October 3, 2014</study_first_submitted>
  <study_first_submitted_qc>October 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 8, 2014</study_first_posted>
  <last_update_submitted>March 17, 2015</last_update_submitted>
  <last_update_submitted_qc>March 17, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 18, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>microbiota</keyword>
  <keyword>FODMAP</keyword>
  <keyword>oligofructose</keyword>
  <keyword>Magnetic Resonance Imaging</keyword>
  <keyword>Metabolomics</keyword>
  <keyword>Diet</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Irritable Bowel Syndrome</mesh_term>
  </condition_browse>
  <!-- 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/NCT02259465
org study id: SoM A14082014 FOG
nct id: NCT02259465
lead sponsor: 
collaborator: 
has dmc: No
Some carbohydrates, complex sugars, which are found in grains, fruit and vegetables, cannot
      be digested by humans. When eaten they pass through the small bowel to the large bowel, or
      colon. Some bacteria that live in the colon are able to digest these carbohydrates, and use
      them as an energy source. This releases energy that humans can absorb, and may have other
      effects on health as well. The process also releases gases such as hydrogen and methane into
      the colon, which will eventually be released as flatulence.

      There is some evidence in animals, and humans, that changing the carbohydrate content of the
      diet may increase the numbers of bacteria in the colon that can use this energy source.
      Recent work has looked at how changes in colon bacteria and carbohydrate in the diet affect
      transit, the speed at which food and stool moves through the stomach and bowels.

      This undergraduate project will use techniques in Magnetic Resonance Imaging developed in
      Nottingham to investigate how a prolonged change in dietary carbohydrate might affect speed
      of transit through the bowel and gas production in the colon, and whether there is any immune
      reaction to the carbohydrate from the bowel wall.
Oligofructose (OF) is a fructose- based oligosaccharide and defined in the European Union as
      a dietary fibre. Enzymatically derived from the longer chain inulin in chicory, it is
      commonly used in processed food to improve mouth feel in fat-free products. OF is poorly
      digested and absorbed in the small bowel so passes to the colon where it is fermented by the
      bacteria usually resident in the colon, termed the microbiota. This process produces gases
      such as hydrogen and sometimes methane, and short-chain fatty acids (SCFAs) which have a
      variety of roles including nutrition to colonocytes, immunological effects and modulation of
      intestinal motility. Its presence in the colon alters the composition of the microbiota, with
      reported potential benefits to health, leading to its description as a 'prebiotic'.

      Recently, however, such poorly digested carbohydrates grouped together by the term FODMAP
      (fermentable oligo-, di-, mono-saccharides and polyols) have been proposed to exacerbate
      symptoms of irritable bowel syndrome (IBS) such as abdominal discomfort and bloating. Dietary
      exclusion of foods containing FODMAPs, such as wheat, dairy and certain fruit and vegetables,
      has been proposed as a treatment for IBS, with some evidence to support this. FODMAPs are
      thought to induce symptoms either by drawing water into the small bowel by osmosis, or
      through gaseous distension of the large bowel or a combination of these along with metabolite
      effects on motility.

      The Nottingham GI MRI group has been at the forefront of elucidating the actual effects of
      FODMAPs on gastrointestinal (GI) physiology. We have published techniques to measure small
      bowel water content, colonic volume and gas volume and whole gut transit time. We have
      recently demonstrated that a single, large (40g) dose of inulin leads to an increase in
      colonic volume, mainly through an increase in colonic gas. Such a dose is beyond the usual
      range of dietary variation, however. Last year we piloted a model more similar to dietary
      practice. Participants supplemented their usual diet with 5g OF twice daily for a week. The
      most striking result was an 18% increase in fasting colonic volume. This could not be
      explained by changes in colonic gas and may represent proliferation, and increased mass, of
      the microbiota. That study was an open label, uncontrolled case series so we now wish to test
      the hypothesis in a double-blind, randomised controlled trial. For explanatory purposes we
      will also measure whole gut transit, colonic gas volume and hydrogen and methane expired in
      the breath. For exploratory purposes we will also collect stool and urine samples to allow
      assessment of the effect on microbiota and their metabolic output.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in colonic volume
time frame: one week
description: Percentage change from baseline in fasting colonic volume after one week of intervention, as measured by Magnetic Resonance Imaging (MRI)
measure: Change in whole gut transit time
time frame: one week
description: Change in whole gut transit time (WGTT) after one week of intervention, as determined by Weighted Average Position Score (WAPS) of MRI transit markers 24 hours after ingestion
measure: Change in colonic gas volume
time frame: one week
description: Percentage change in fasting colonic gas volume after one week of intervention, as measured by MRI
measure: Change in fasting breath hydrogen
time frame: one week
description: Change in fasting breath hydrogen concentration after one week of intervention, measured in parts per million
measure: Change in fasting breath methane
time frame: one week
description: Change in fasting breath methane concentration after one week of intervention, measured in parts per million
measure: Change in urinary metabolites
time frame: one week
description: Exploratory work to assess change in urinary metabolite concentrations after one week of intervention
measure: Change in faecal microbiota
time frame: one week
description: Exploratory work to assess change in faecal microbiota concentrations after one week of intervention
measure: Change in faecal short-chain fatty acids
time frame: one week
description: Exploratory work to assess change in faecal short-chain fatty acid concentrations after one week of intervention
arm group label: Oligofructose
arm group type: Active Comparator
description: Participants will be asked to follow the low FODMAP diet for a week, supplementing the diet with oligofructose, 7grams twice daily
arm group label: Maltodextrin
arm group type: Placebo Comparator
description: Participants will be asked to follow the low FODMAP diet for a week, supplementing the diet with maltodextrin, 7grams twice daily
intervention type: Behavioral
intervention name: low FODMAP diet
description: Participants will attend a one-hour group session on how to follow the low FODMAP diet, run by a dietitian trained in the diet. They will be asked to follow the diet for 7 days while keeping a food diary.
arm group label: Maltodextrin
arm group label: Oligofructose
intervention type: Dietary Supplement
intervention name: Oligofructose
description: Participants will supplement their diet with 7 grams of OF twice daily for the week that they follow the low FODMAP diet.
arm group label: Oligofructose
other name: OraftiP95, OF
intervention type: Dietary Supplement
intervention name: Maltodextrin
description: Participants will supplement their diet with 7 grams of maltodextrin twice daily for the week that they follow the low FODMAP diet.
arm group label: Maltodextrin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Robin C Spiller, MD FRCP
role: Study Chair
affiliation: University of Nottingham
last name: Giles AD Major, BMBCh MRCP
role: Principal Investigator
affiliation: University of Nottingham
facility: 
country: United Kingdom
url: http://www.nddcbru.org.uk
description: Related Info
url: https://www.facebook.com/UoN.Gastrointestinal.MRI
description: Related Info
responsible party type: Sponsor
mesh term: Irritable Bowel Syndrome