<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/NCT03265002</url>
  </required_header>
  <id_info>
    <org_study_id>17056</org_study_id>
    <nct_id>NCT03265002</nct_id>
  </id_info>
  <brief_title>Fibre and Gas in Irritable Bowel Syndrome</brief_title>
  <acronym>EFIGI</acronym>
  <official_title>Effects of Fibre on Intestinal Volume and Gas in Irritable Bowel Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Nottingham</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Nottingham</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of the study is to investigate how dietary fibre combinations affects gut physiology,&#xD;
      particularly colonic gas production. Comparisons will be made between a single fermentable&#xD;
      fibre (inulin), a non-fermentable fibre (psyllium) and a combination of the two. The study&#xD;
      will also explore differences in response between diarrhoea-predominant and&#xD;
      constipation-predominant IBS (IBS-D and IBS-C) respectively.&#xD;
&#xD;
      The participants will have a preliminary meeting to ensure they are eligible, then will&#xD;
      attend the MRI department on 4 occasions separated by at least 1 week. They will ingest a&#xD;
      drink with the fibre product mixed in, and will have 8 MRI scans (each lasting approximately&#xD;
      15 minutes).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The aim of the study is to investigate how dietary fibre combinations affects gut physiology,&#xD;
      particularly colonic gas production. Comparisons will be made between a single fermentable&#xD;
      fibre (inulin), a non-fermentable fibre (psyllium) and a combination of the two. The study&#xD;
      will also explore differences in response between diarrhoea-predominant and&#xD;
      constipation-predominant IBS (IBS-D and IBS-C) respectively.&#xD;
&#xD;
      This is a single-centre, 4-period, 4-treatment, placebo-controlled, crossover trial. Each&#xD;
      treatment will be taken once by each participant, with randomisation of treatment order.&#xD;
&#xD;
      The staff responsible for preparing this food will be members of the digestive diseases unit&#xD;
      at the NIHR Nottingham Biomedical Research Centre and will not be involved in the study&#xD;
      otherwise. The investigators responsible for MRI and symptom analysis will be kept blind to&#xD;
      the intervention as data will be coded by date of study day, rather than by product received.&#xD;
      Additionally MRI data will be assigned a 'scanning number' through the Sir Peter Mansfield&#xD;
      Imaging Centre. This will pseudo-anonymise MRI data within the study so that associations&#xD;
      between participants and scans will not be immediately obvious.&#xD;
&#xD;
      Randomisation All participants will take all 4 fibre/ placebo preparations in this crossover&#xD;
      trial but the order in which the participants take them will be randomised. The randomisation&#xD;
      will be undertaken by a member of the research division who is independent of the study using&#xD;
      the remote, online, open source software www.randomization.com. The resulting code will be&#xD;
      retained by staff responsible for food preparation in paper form, and will not be shared with&#xD;
      the investigator team. A paper copy will be kept by the CI in a sealed envelope.&#xD;
&#xD;
      On enrolment to the study, participants will be allotted the next available randomization&#xD;
      sequence. No stratification is needed as in a crossover design participants act as their own&#xD;
      controls. There will be a washout period of at least one week between each study day to&#xD;
      minimise any carryover effect.&#xD;
&#xD;
      Expected duration of participant participation Study participants will be participating in&#xD;
      the study for 6-8 weeks. Women will not be scanned during their menstrual period to avoid&#xD;
      confounding of symptom responses.&#xD;
&#xD;
      The study consists of 5 visits to the Queens Medical Centre, Nottingham (QMC). Visits will be&#xD;
      in University departments embedded in the hospital, either in the Nottingham Digestive&#xD;
      Diseases Centre (NDDC) or the Level A annex of the Sir Peter Mansfield Imaging Centre&#xD;
      (SPMIC).&#xD;
&#xD;
      The first visit will be to take consent, assess eligibility and record baseline covariates of&#xD;
      interest. All subsequent visits will MRI study days, where participants will undergo a series&#xD;
      of MRI scans and other assessments.&#xD;
&#xD;
      Visit 1 This visit will last around 30 minutes. The researcher will confirm that the&#xD;
      potential participant has understood the information sheet and answer any remaining&#xD;
      questions. The participant will then be assessed for eligibility against the criteria&#xD;
      previously set out. If eligibility is confirmed, participants will be asked for details of&#xD;
      current medication use including contraception, smoking status, and significant past medical&#xD;
      history. Height and weight will be recorded. Participants will complete the Hospital Anxiety&#xD;
      and Depression Scale and the Patient Health Questionnaire-12. These questionnaires measure&#xD;
      psychological traits that have been associated with symptom response in IBS and so will be&#xD;
      relevant covariates.&#xD;
&#xD;
      Participants will then begin a 7-day screening diary of bowel habit and symptoms. This will&#xD;
      be used to confirm frequency of IBS symptoms and IBS subtype. Participants will complete the&#xD;
      Rome IV diagnostic questionnaire as part of their eligibility assessment. If there is a&#xD;
      discrepancy between diary data and participant report on the Rome IV questionnaire, then the&#xD;
      PI may decide to exclude the participant. To reduce patient burden, it will be acceptable to&#xD;
      return completed diaries by post (prepaid envelope), by electronic communication (scan or&#xD;
      photo), or in person.&#xD;
&#xD;
      Participants will also be informed that their GP will be contacted, both to inform them of&#xD;
      the subject's participation and to confirm medical details where required.&#xD;
&#xD;
      Once eligibility has been confirmed, the Participant will be enrolled and randomised to a&#xD;
      sequence of treatments. These will be administered during Visits 2 - 5. Participants will be&#xD;
      asked to minimise their intake of fermentable carbohydrates on the day preceding each of&#xD;
      these visits in addition to having a standardised evening meal. A dietary advice sheet will&#xD;
      be provided.&#xD;
&#xD;
      Visits 2 - 5: MRI Study Days MRI study days will take place in the level A annex of the&#xD;
      SPMIC, in the QMC. Visits will be at least 1 week apart to minimise any carryover effect.&#xD;
      Participants will fast from 8pm on the evening before the Study Day. Water will be permitted&#xD;
      after 8pm. On the morning of the Study Day participants will not eat or drink, other than a&#xD;
      few sips of water to assist swallowing of essential medicines.&#xD;
&#xD;
      It will be confirmed that participants remain safe, eligible and willing to take part. The&#xD;
      participants will change into surgical scrubs, in line with scanning policy and will then&#xD;
      complete the first set of assessments.&#xD;
&#xD;
      The assessments will be:&#xD;
&#xD;
        1. Report of gastrointestinal symptoms. Symptoms of wind/ flatulence, bloating and&#xD;
           abdominal pain will be scored on a 7-point scale, 0 - 3 in half-integer intervals(5).&#xD;
&#xD;
        2. Measurement of breath hydrogen and methane content from a single forced exhalation,&#xD;
           using the GastroCheck device (Bedfont, UK).&#xD;
&#xD;
        3. An MRI scan including various scan sequences (See MRI Analysis section)&#xD;
&#xD;
      After fasting assessment participants will ingest a Test Drink. This will comprise still&#xD;
      water made up to 500mL with 50mL lemon juice (PLj, Holland&amp;Barrett, UK), into which the test&#xD;
      supplement will be mixed.&#xD;
&#xD;
      The Test Fibres used will be:&#xD;
&#xD;
      A. 20g Inulin B. 20g Inulin and 20g psyllium C. 20g psyllium D. 20g dextrose (0g fibre&#xD;
      content - placebo control)&#xD;
&#xD;
      The test drink will be administered in 2 x 250mL portions to prevent swelling of fibres.&#xD;
      Participants will be given 10 minutes to consume the total 500mls.&#xD;
&#xD;
      Assessments will be repeated immediately after ingestion, then at intervals post-ingestion as&#xD;
      shown in the schematic. Breath symptoms will be measured every 30 minutes for 2 hours, then&#xD;
      hourly. MRIs will be taken immediately post ingestion, then hourly for 6 hours. After 3 hours&#xD;
      a meal will be provided, designed to be low in fermentable carbohydrate and fibre. This will&#xD;
      stimulate gut motility and movement of small bowel content into the colon. The whole Study&#xD;
      Day will last around 8 hours.&#xD;
&#xD;
      At the end of the Study Day participants will be asked for an overall rating of their&#xD;
      symptoms throughout the day, and an assessment of product acceptability on the basis of their&#xD;
      experience (0 - 100 visual analogue scale).&#xD;
&#xD;
      In between assessments participants will be provided with a comfortable sitting area which is&#xD;
      part of the level A annex. The participants will be advised to bring material such as&#xD;
      magazines, books or electronic devices for entertainment. Guest access to the university's&#xD;
      wireless internet (wifi) network will be available.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 8, 2018</start_date>
  <completion_date type="Actual">October 16, 2019</completion_date>
  <primary_completion_date type="Actual">October 16, 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>Crossover Assignment</intervention_model>
    <intervention_model_description>single-centre, 4 period, 4 treatment, placebo-controlled crossover trial.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>Participants will be blind to the fibre product taken on each study visit. Masking will be assisted by adding lemon juice to the vehicle drink.&#xD;
The staff responsible for preparing this food will be members of the digestive diseases unit at the NIHR Nottingham Biomedical Research Centre and will not be involved in the study otherwise. The investigators responsible for MRI and symptom analysis will be kept blind to the intervention as data will be coded by date of study day, rather than by product received. Additionally MRI data will be assigned a 'scanning number' through the Sir Peter Mansfield Imaging Centre. This will pseudo-anonymise MRI data within the study so that associations between participants and scans will not be immediately obvious.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change from the baseline in colonic gas</measure>
    <time_frame>baseline, 0, 1, 2, 3, 4, 5 and 6 hours post ingestion of the fibre drink</time_frame>
    <description>in arbitrary units measured by MRI</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from the baseline in colonic volume</measure>
    <time_frame>baseline, 0, 1, 2, 3, 4, 5 and 6 hours post ingestion of the fibre drink</time_frame>
    <description>in mL measured by MRI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from the baseline in small bowel water content</measure>
    <time_frame>baseline, 0, 1, 2, 3, 4, 5 and 6 hours post ingestion of the fibre drink</time_frame>
    <description>in mL measured by MRI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from the baseline in breath hydrogen</measure>
    <time_frame>baseline, 0mins, 30mins, 1 hour, 90mins, 2 hours, 3, 4, 5 and 6 hours post ingestion of fibre drink</time_frame>
    <description>in parts per million using the GastroCheck device</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from the baseline in severity of pain, bloating and flatulence</measure>
    <time_frame>baseline, 0mins, 30mins, 1 hour, 90mins, 2 hours, 3, 4, 5 and 6 hours post ingestion of fibre drink</time_frame>
    <description>assessed by the Gastrointestinal Symptom Rating Scale, using a 7-point scale</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Product acceptability</measure>
    <time_frame>throughout the study completion, measured after the 6 hour postprandial measurements.</time_frame>
    <description>gained by questionnaire</description>
  </other_outcome>
  <other_outcome>
    <measure>Change from the baseline in contractility of the ascending colon</measure>
    <time_frame>baseline, 0, 1, 2, 3, 4, 5 and 6 hours post ingestion of the fibre drink</time_frame>
    <description>assessed by the MRI motility index</description>
  </other_outcome>
  <other_outcome>
    <measure>breath methane</measure>
    <time_frame>baseline, 0mins, 30mins, 1 hour, 90mins, 2 hours, 3, 4, 5 and 6 hours post ingestion of fibre drink</time_frame>
    <description>in parts per million using the GastroCheck device</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Irritable Bowel Syndrome</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Ingestion of 500ml water with 50ml lemon juice and 20g dextrose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Inulin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ingestion of 500ml water with 50ml lemon juice and 20g inulin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Psyllium</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ingestion of 500ml water with 50ml lemon juice and 20g psyllium</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Inulin and Psyllium</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ingestion of 500ml water with 50ml lemon juice and 20g inulin and 20g psyllium</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Ingestion of 500ml water with 50ml lemon juice and 20g dextrose</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Inulin</intervention_name>
    <description>Ingestion of 500ml water with 50ml lemon juice and 20g inulin</description>
    <arm_group_label>Inulin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Psyllium</intervention_name>
    <description>Ingestion of 500ml water with 50ml lemon juice and 20g psyllium</description>
    <arm_group_label>Psyllium</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Inulin and psyllium</intervention_name>
    <description>Ingestion of 500ml water with 50ml lemon juice and 20g inulin and 20g psyllium</description>
    <arm_group_label>Inulin and Psyllium</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ability to give informed consent&#xD;
&#xD;
          -  Fulfilment of the Rome IV criteria for Irritable Bowel Syndrome for at least 3 months:&#xD;
&#xD;
               -  Abdominal pain at least two or more days per week.&#xD;
&#xD;
               -  Pain associated with two or more of the following:&#xD;
&#xD;
                    -  Related to defecation on at least ≥30% of occasions&#xD;
&#xD;
                    -  Associated with a change in frequency of stool on ≥30% of occasions&#xD;
&#xD;
                    -  Associated with a change in form (appearance) of stool on ≥30% of occasions&#xD;
&#xD;
               -  Symptom onset at least 6 months prior to diagnosis&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy declared by candidate&#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;
          -  Inability to lie flat or exceed scanner limits of weight &lt;120kg&#xD;
&#xD;
          -  Unwilling to cease use of supplementary fibre or osmotic laxatives for the duration of&#xD;
             the study&#xD;
&#xD;
          -  Unable to stop drugs known to alter GI motility or transit including mebeverine,&#xD;
             opiates, monoamine oxidase inhibitors, phenothiazines, benzodiazepines, calcium&#xD;
             channel antagonists or osmotic laxatives for 2 days before, and during, MRI study&#xD;
             days.&#xD;
&#xD;
               -  Selective serotonin reuptake inhibitors and low dose tricyclic antidepressants&#xD;
                  will be recorded but will not be an exclusion criteria&#xD;
&#xD;
          -  Reported alcohol intake of &gt;28 units/ week with daily drinking&#xD;
&#xD;
          -  Intention to change smoking behaviour during the study&#xD;
&#xD;
          -  History declared by the candidate of other pre-existing gastrointestinal disorders,&#xD;
             including but not limited to:&#xD;
&#xD;
               -  Inflammatory Bowel Disease&#xD;
&#xD;
               -  Coeliac Disease&#xD;
&#xD;
               -  Pancreatitis&#xD;
&#xD;
               -  Gallstone disease (biliary colic, cholecystitis; asymptomatic presence of&#xD;
                  gallstones permitted)&#xD;
&#xD;
               -  Complicated diverticulitis (asymptomatic presence of diverticula permitted)&#xD;
&#xD;
               -  Cancer of the gastrointestinal tract&#xD;
&#xD;
               -  Gastroparesis&#xD;
&#xD;
               -  Other functional gastrointestinal disorders will be permitted as they frequently&#xD;
                  co-exist with IBS.&#xD;
&#xD;
          -  Any reported history of gastrointestinal resection (excluding appendicectomy or&#xD;
             cholecystectomy)&#xD;
&#xD;
          -  Presence of an intestinal stoma&#xD;
&#xD;
          -  Poor understanding of English language&#xD;
&#xD;
          -  Participation of any medical trials for the past 3 months&#xD;
&#xD;
          -  Judgement by the PI that the candidate who will be unable to comply with the full&#xD;
             study protocol e.g. Diabetes, severe COPD&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Robin Spiller, Ph, BMBS</last_name>
    <role>Study Chair</role>
    <affiliation>University of Nottingham</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Nottingham</name>
      <address>
        <city>Nottingham</city>
        <state>Nottinghamshire</state>
        <zip>NG7 2UH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Major G, Pritchard S, Murray K, Alappadan JP, Hoad CL, Marciani L, Gowland P, Spiller R. Colon Hypersensitivity to Distension, Rather Than Excessive Gas Production, Produces Carbohydrate-Related Symptoms in Individuals With Irritable Bowel Syndrome. Gastroenterology. 2017 Jan;152(1):124-133.e2. doi: 10.1053/j.gastro.2016.09.062. Epub 2016 Oct 14.</citation>
    <PMID>27746233</PMID>
  </reference>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>August 23, 2017</study_first_submitted>
  <study_first_submitted_qc>August 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 29, 2017</study_first_posted>
  <last_update_submitted>March 24, 2020</last_update_submitted>
  <last_update_submitted_qc>March 24, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 25, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>fibre</keyword>
  <keyword>inulin</keyword>
  <keyword>psyllium</keyword>
  <keyword>small bowel MRI</keyword>
  <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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Psyllium</mesh_term>
    <mesh_term>Calcium polycarbophil</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/NCT03265002
org study id: 17056
nct id: NCT03265002
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
The aim of the study is to investigate how dietary fibre combinations affects gut physiology,
      particularly colonic gas production. Comparisons will be made between a single fermentable
      fibre (inulin), a non-fermentable fibre (psyllium) and a combination of the two. The study
      will also explore differences in response between diarrhoea-predominant and
      constipation-predominant IBS (IBS-D and IBS-C) respectively.

      The participants will have a preliminary meeting to ensure they are eligible, then will
      attend the MRI department on 4 occasions separated by at least 1 week. They will ingest a
      drink with the fibre product mixed in, and will have 8 MRI scans (each lasting approximately
      15 minutes).
The aim of the study is to investigate how dietary fibre combinations affects gut physiology,
      particularly colonic gas production. Comparisons will be made between a single fermentable
      fibre (inulin), a non-fermentable fibre (psyllium) and a combination of the two. The study
      will also explore differences in response between diarrhoea-predominant and
      constipation-predominant IBS (IBS-D and IBS-C) respectively.

      This is a single-centre, 4-period, 4-treatment, placebo-controlled, crossover trial. Each
      treatment will be taken once by each participant, with randomisation of treatment order.

      The staff responsible for preparing this food will be members of the digestive diseases unit
      at the NIHR Nottingham Biomedical Research Centre and will not be involved in the study
      otherwise. The investigators responsible for MRI and symptom analysis will be kept blind to
      the intervention as data will be coded by date of study day, rather than by product received.
      Additionally MRI data will be assigned a 'scanning number' through the Sir Peter Mansfield
      Imaging Centre. This will pseudo-anonymise MRI data within the study so that associations
      between participants and scans will not be immediately obvious.

      Randomisation All participants will take all 4 fibre/ placebo preparations in this crossover
      trial but the order in which the participants take them will be randomised. The randomisation
      will be undertaken by a member of the research division who is independent of the study using
      the remote, online, open source software www.randomization.com. The resulting code will be
      retained by staff responsible for food preparation in paper form, and will not be shared with
      the investigator team. A paper copy will be kept by the CI in a sealed envelope.

      On enrolment to the study, participants will be allotted the next available randomization
      sequence. No stratification is needed as in a crossover design participants act as their own
      controls. There will be a washout period of at least one week between each study day to
      minimise any carryover effect.

      Expected duration of participant participation Study participants will be participating in
      the study for 6-8 weeks. Women will not be scanned during their menstrual period to avoid
      confounding of symptom responses.

      The study consists of 5 visits to the Queens Medical Centre, Nottingham (QMC). Visits will be
      in University departments embedded in the hospital, either in the Nottingham Digestive
      Diseases Centre (NDDC) or the Level A annex of the Sir Peter Mansfield Imaging Centre
      (SPMIC).

      The first visit will be to take consent, assess eligibility and record baseline covariates of
      interest. All subsequent visits will MRI study days, where participants will undergo a series
      of MRI scans and other assessments.

      Visit 1 This visit will last around 30 minutes. The researcher will confirm that the
      potential participant has understood the information sheet and answer any remaining
      questions. The participant will then be assessed for eligibility against the criteria
      previously set out. If eligibility is confirmed, participants will be asked for details of
      current medication use including contraception, smoking status, and significant past medical
      history. Height and weight will be recorded. Participants will complete the Hospital Anxiety
      and Depression Scale and the Patient Health Questionnaire-12. These questionnaires measure
      psychological traits that have been associated with symptom response in IBS and so will be
      relevant covariates.

      Participants will then begin a 7-day screening diary of bowel habit and symptoms. This will
      be used to confirm frequency of IBS symptoms and IBS subtype. Participants will complete the
      Rome IV diagnostic questionnaire as part of their eligibility assessment. If there is a
      discrepancy between diary data and participant report on the Rome IV questionnaire, then the
      PI may decide to exclude the participant. To reduce patient burden, it will be acceptable to
      return completed diaries by post (prepaid envelope), by electronic communication (scan or
      photo), or in person.

      Participants will also be informed that their GP will be contacted, both to inform them of
      the subject's participation and to confirm medical details where required.

      Once eligibility has been confirmed, the Participant will be enrolled and randomised to a
      sequence of treatments. These will be administered during Visits 2 - 5. Participants will be
      asked to minimise their intake of fermentable carbohydrates on the day preceding each of
      these visits in addition to having a standardised evening meal. A dietary advice sheet will
      be provided.

      Visits 2 - 5: MRI Study Days MRI study days will take place in the level A annex of the
      SPMIC, in the QMC. Visits will be at least 1 week apart to minimise any carryover effect.
      Participants will fast from 8pm on the evening before the Study Day. Water will be permitted
      after 8pm. On the morning of the Study Day participants will not eat or drink, other than a
      few sips of water to assist swallowing of essential medicines.

      It will be confirmed that participants remain safe, eligible and willing to take part. The
      participants will change into surgical scrubs, in line with scanning policy and will then
      complete the first set of assessments.

      The assessments will be:

        1. Report of gastrointestinal symptoms. Symptoms of wind/ flatulence, bloating and
           abdominal pain will be scored on a 7-point scale, 0 - 3 in half-integer intervals(5).

        2. Measurement of breath hydrogen and methane content from a single forced exhalation,
           using the GastroCheck device (Bedfont, UK).

        3. An MRI scan including various scan sequences (See MRI Analysis section)

      After fasting assessment participants will ingest a Test Drink. This will comprise still
      water made up to 500mL with 50mL lemon juice (PLj, Holland&Barrett, UK), into which the test
      supplement will be mixed.

      The Test Fibres used will be:

      A. 20g Inulin B. 20g Inulin and 20g psyllium C. 20g psyllium D. 20g dextrose (0g fibre
      content - placebo control)

      The test drink will be administered in 2 x 250mL portions to prevent swelling of fibres.
      Participants will be given 10 minutes to consume the total 500mls.

      Assessments will be repeated immediately after ingestion, then at intervals post-ingestion as
      shown in the schematic. Breath symptoms will be measured every 30 minutes for 2 hours, then
      hourly. MRIs will be taken immediately post ingestion, then hourly for 6 hours. After 3 hours
      a meal will be provided, designed to be low in fermentable carbohydrate and fibre. This will
      stimulate gut motility and movement of small bowel content into the colon. The whole Study
      Day will last around 8 hours.

      At the end of the Study Day participants will be asked for an overall rating of their
      symptoms throughout the day, and an assessment of product acceptability on the basis of their
      experience (0 - 100 visual analogue scale).

      In between assessments participants will be provided with a comfortable sitting area which is
      part of the level A annex. The participants will be advised to bring material such as
      magazines, books or electronic devices for entertainment. Guest access to the university's
      wireless internet (wifi) network will be available.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: single-centre, 4 period, 4 treatment, placebo-controlled crossover trial.
primary purpose: Basic Science
masking: Double (Participant, Investigator)
masking description: Participants will be blind to the fibre product taken on each study visit. Masking will be assisted by adding lemon juice to the vehicle drink.
The staff responsible for preparing this food will be members of the digestive diseases unit at the NIHR Nottingham Biomedical Research Centre and will not be involved in the study otherwise. The investigators responsible for MRI and symptom analysis will be kept blind to the intervention as data will be coded by date of study day, rather than by product received. Additionally MRI data will be assigned a 'scanning number' through the Sir Peter Mansfield Imaging Centre. This will pseudo-anonymise MRI data within the study so that associations between participants and scans will not be immediately obvious.
measure: Change from the baseline in colonic gas
time frame: baseline, 0, 1, 2, 3, 4, 5 and 6 hours post ingestion of the fibre drink
description: in arbitrary units measured by MRI
measure: Change from the baseline in colonic volume
time frame: baseline, 0, 1, 2, 3, 4, 5 and 6 hours post ingestion of the fibre drink
description: in mL measured by MRI
measure: Change from the baseline in small bowel water content
time frame: baseline, 0, 1, 2, 3, 4, 5 and 6 hours post ingestion of the fibre drink
description: in mL measured by MRI
measure: Change from the baseline in breath hydrogen
time frame: baseline, 0mins, 30mins, 1 hour, 90mins, 2 hours, 3, 4, 5 and 6 hours post ingestion of fibre drink
description: in parts per million using the GastroCheck device
measure: Change from the baseline in severity of pain, bloating and flatulence
time frame: baseline, 0mins, 30mins, 1 hour, 90mins, 2 hours, 3, 4, 5 and 6 hours post ingestion of fibre drink
description: assessed by the Gastrointestinal Symptom Rating Scale, using a 7-point scale
measure: Product acceptability
time frame: throughout the study completion, measured after the 6 hour postprandial measurements.
description: gained by questionnaire
measure: Change from the baseline in contractility of the ascending colon
time frame: baseline, 0, 1, 2, 3, 4, 5 and 6 hours post ingestion of the fibre drink
description: assessed by the MRI motility index
measure: breath methane
time frame: baseline, 0mins, 30mins, 1 hour, 90mins, 2 hours, 3, 4, 5 and 6 hours post ingestion of fibre drink
description: in parts per million using the GastroCheck device
arm group label: Placebo
arm group type: Placebo Comparator
description: Ingestion of 500ml water with 50ml lemon juice and 20g dextrose
arm group label: Inulin
arm group type: Experimental
description: Ingestion of 500ml water with 50ml lemon juice and 20g inulin
arm group label: Psyllium
arm group type: Active Comparator
description: Ingestion of 500ml water with 50ml lemon juice and 20g psyllium
arm group label: Inulin and Psyllium
arm group type: Active Comparator
description: Ingestion of 500ml water with 50ml lemon juice and 20g inulin and 20g psyllium
intervention type: Dietary Supplement
intervention name: Placebo
description: Ingestion of 500ml water with 50ml lemon juice and 20g dextrose
arm group label: Placebo
intervention type: Dietary Supplement
intervention name: Inulin
description: Ingestion of 500ml water with 50ml lemon juice and 20g inulin
arm group label: Inulin
intervention type: Dietary Supplement
intervention name: Psyllium
description: Ingestion of 500ml water with 50ml lemon juice and 20g psyllium
arm group label: Psyllium
intervention type: Dietary Supplement
intervention name: Inulin and psyllium
description: Ingestion of 500ml water with 50ml lemon juice and 20g inulin and 20g psyllium
arm group label: Inulin and Psyllium
criteria: 
gender: All
minimum age: 16 Years
maximum age: 65 Years
healthy volunteers: No
last name: Robin Spiller, Ph, BMBS
role: Study Chair
affiliation: University of Nottingham
facility: 
country: United Kingdom
citation: Major G, Pritchard S, Murray K, Alappadan JP, Hoad CL, Marciani L, Gowland P, Spiller R. Colon Hypersensitivity to Distension, Rather Than Excessive Gas Production, Produces Carbohydrate-Related Symptoms in Individuals With Irritable Bowel Syndrome. Gastroenterology. 2017 Jan;152(1):124-133.e2. doi: 10.1053/j.gastro.2016.09.062. Epub 2016 Oct 14.
PMID: 27746233
responsible party type: Sponsor
mesh term: Irritable Bowel Syndrome
mesh term: Syndrome
mesh term: Psyllium
mesh term: Calcium polycarbophil
sharing ipd: No