Fibre and Gas in Irritable Bowel Syndrome
Condition: Irritable Bowel Syndrome
MeSH terms: Irritable Bowel Syndrome; Syndrome
Study type: Interventional

Summary: 
      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).
    

Detailed description: 
      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.
    

Intervention name(s): Placebo; Inulin; Psyllium; Inulin and psyllium
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): Ingestion of 500ml water with 50ml lemon juice and 20g dextrose; Ingestion of 500ml water with 50ml lemon juice and 20g inulin; Ingestion of 500ml water with 50ml lemon juice and 20g psyllium; Ingestion of 500ml water with 50ml lemon juice and 20g inulin and 20g psyllium
Intervention MeSH terms: Psyllium; Calcium polycarbophil
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: single-centre, 4 period, 4 treatment, placebo-controlled crossover trial.
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: fibre; inulin; psyllium; small bowel MRI