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Fibre and Gas in Irritable Bowel Syndrome (EFIGI)

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ClinicalTrials.gov Identifier: NCT03265002
Recruitment Status : Completed
First Posted : August 29, 2017
Last Update Posted : March 25, 2020
Sponsor:
Information provided by (Responsible Party):
University of Nottingham

Tracking Information
First Submitted Date  ICMJE August 23, 2017
First Posted Date  ICMJE August 29, 2017
Last Update Posted Date March 25, 2020
Actual Study Start Date  ICMJE March 8, 2018
Actual Primary Completion Date October 16, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 28, 2017)
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 ]
in arbitrary units measured by MRI
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 28, 2017)
  • 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 ]
    in mL measured by MRI
  • 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 ]
    in mL measured by MRI
  • 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 ]
    in parts per million using the GastroCheck device
  • 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 ]
    assessed by the Gastrointestinal Symptom Rating Scale, using a 7-point scale
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: August 28, 2017)
  • Product acceptability [ Time Frame: throughout the study completion, measured after the 6 hour postprandial measurements. ]
    gained by questionnaire
  • 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 ]
    assessed by the MRI motility index
  • breath methane [ Time Frame: baseline, 0mins, 30mins, 1 hour, 90mins, 2 hours, 3, 4, 5 and 6 hours post ingestion of fibre drink ]
    in parts per million using the GastroCheck device
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Fibre and Gas in Irritable Bowel Syndrome
Official Title  ICMJE Effects of Fibre on Intestinal Volume and Gas in Irritable Bowel Syndrome
Brief 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
single-centre, 4 period, 4 treatment, placebo-controlled crossover trial.
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.

Primary Purpose: Basic Science
Condition  ICMJE Irritable Bowel Syndrome
Intervention  ICMJE
  • Dietary Supplement: Placebo
    Ingestion of 500ml water with 50ml lemon juice and 20g dextrose
  • Dietary Supplement: Inulin
    Ingestion of 500ml water with 50ml lemon juice and 20g inulin
  • Dietary Supplement: Psyllium
    Ingestion of 500ml water with 50ml lemon juice and 20g psyllium
  • Dietary Supplement: Inulin and psyllium
    Ingestion of 500ml water with 50ml lemon juice and 20g inulin and 20g psyllium
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Ingestion of 500ml water with 50ml lemon juice and 20g dextrose
    Intervention: Dietary Supplement: Placebo
  • Experimental: Inulin
    Ingestion of 500ml water with 50ml lemon juice and 20g inulin
    Intervention: Dietary Supplement: Inulin
  • Active Comparator: Psyllium
    Ingestion of 500ml water with 50ml lemon juice and 20g psyllium
    Intervention: Dietary Supplement: Psyllium
  • Active Comparator: Inulin and Psyllium
    Ingestion of 500ml water with 50ml lemon juice and 20g inulin and 20g psyllium
    Intervention: Dietary Supplement: Inulin and psyllium
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 24, 2020)
19
Original Estimated Enrollment  ICMJE
 (submitted: August 28, 2017)
25
Actual Study Completion Date  ICMJE October 16, 2019
Actual Primary Completion Date October 16, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Ability to give informed consent
  • Fulfilment of the Rome IV criteria for Irritable Bowel Syndrome for at least 3 months:

    • Abdominal pain at least two or more days per week.
    • Pain associated with two or more of the following:

      • Related to defecation on at least ≥30% of occasions
      • Associated with a change in frequency of stool on ≥30% of occasions
      • Associated with a change in form (appearance) of stool on ≥30% of occasions
    • Symptom onset at least 6 months prior to diagnosis

Exclusion Criteria:

  • Pregnancy declared by candidate
  • Contraindications for MRI scanning i.e. metallic implants, pacemakers, history of metallic foreign body in eye(s) and penetrating eye injury
  • Inability to lie flat or exceed scanner limits of weight <120kg
  • Unwilling to cease use of supplementary fibre or osmotic laxatives for the duration of the study
  • Unable to stop drugs known to alter GI motility or transit including mebeverine, opiates, monoamine oxidase inhibitors, phenothiazines, benzodiazepines, calcium channel antagonists or osmotic laxatives for 2 days before, and during, MRI study days.

    • Selective serotonin reuptake inhibitors and low dose tricyclic antidepressants will be recorded but will not be an exclusion criteria
  • Reported alcohol intake of >28 units/ week with daily drinking
  • Intention to change smoking behaviour during the study
  • History declared by the candidate of other pre-existing gastrointestinal disorders, including but not limited to:

    • Inflammatory Bowel Disease
    • Coeliac Disease
    • Pancreatitis
    • Gallstone disease (biliary colic, cholecystitis; asymptomatic presence of gallstones permitted)
    • Complicated diverticulitis (asymptomatic presence of diverticula permitted)
    • Cancer of the gastrointestinal tract
    • Gastroparesis
    • Other functional gastrointestinal disorders will be permitted as they frequently co-exist with IBS.
  • Any reported history of gastrointestinal resection (excluding appendicectomy or cholecystectomy)
  • Presence of an intestinal stoma
  • Poor understanding of English language
  • Participation of any medical trials for the past 3 months
  • Judgement by the PI that the candidate who will be unable to comply with the full study protocol e.g. Diabetes, severe COPD
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years to 65 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03265002
Other Study ID Numbers  ICMJE 17056
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Nottingham
Study Sponsor  ICMJE University of Nottingham
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Robin Spiller, Ph, BMBS University of Nottingham
PRS Account University of Nottingham
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP