- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03265002
Fibre and Gas in Irritable Bowel Syndrome (EFIGI)
Effects of Fibre on Intestinal Volume and Gas in Irritable Bowel Syndrome
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).
Study Overview
Status
Conditions
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:
- 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).
- Measurement of breath hydrogen and methane content from a single forced exhalation, using the GastroCheck device (Bedfont, UK).
- 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
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Nottinghamshire
-
Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
- University of Nottingham
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
Ingestion of 500ml water with 50ml lemon juice and 20g dextrose
|
Ingestion of 500ml water with 50ml lemon juice and 20g dextrose
|
Experimental: Inulin
Ingestion of 500ml water with 50ml lemon juice and 20g inulin
|
Ingestion of 500ml water with 50ml lemon juice and 20g inulin
|
Active Comparator: Psyllium
Ingestion of 500ml water with 50ml lemon juice and 20g psyllium
|
Ingestion of 500ml water with 50ml lemon juice and 20g psyllium
|
Active Comparator: Inulin and Psyllium
Ingestion of 500ml water with 50ml lemon juice and 20g inulin and 20g psyllium
|
Ingestion of 500ml water with 50ml lemon juice and 20g inulin and 20g psyllium
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
baseline, 0, 1, 2, 3, 4, 5 and 6 hours post ingestion of the fibre drink
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
baseline, 0, 1, 2, 3, 4, 5 and 6 hours post ingestion of the fibre drink
|
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
|
baseline, 0, 1, 2, 3, 4, 5 and 6 hours post ingestion of the fibre drink
|
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
|
baseline, 0mins, 30mins, 1 hour, 90mins, 2 hours, 3, 4, 5 and 6 hours post ingestion of fibre drink
|
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
|
baseline, 0mins, 30mins, 1 hour, 90mins, 2 hours, 3, 4, 5 and 6 hours post ingestion of fibre drink
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Product acceptability
Time Frame: throughout the study completion, measured after the 6 hour postprandial measurements.
|
gained by questionnaire
|
throughout the study completion, measured after the 6 hour postprandial measurements.
|
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
|
baseline, 0, 1, 2, 3, 4, 5 and 6 hours post ingestion of the fibre drink
|
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
|
baseline, 0mins, 30mins, 1 hour, 90mins, 2 hours, 3, 4, 5 and 6 hours post ingestion of fibre drink
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Robin Spiller, Ph, BMBS, University of Nottingham
Publications and helpful links
General Publications
- 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.
- Gunn D, Abbas Z, Harris HC, Major G, Hoad C, Gowland P, Marciani L, Gill SK, Warren FJ, Rossi M, Remes-Troche JM, Whelan K, Spiller RC. Psyllium reduces inulin-induced colonic gas production in IBS: MRI and in vitro fermentation studies. Gut. 2022 May;71(5):919-927. doi: 10.1136/gutjnl-2021-324784. Epub 2021 Aug 5.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 17056
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Irritable Bowel Syndrome
-
ProgenaBiomeRecruitingIrritable Bowel Syndrome | Irritable Bowel Syndrome With Diarrhea | Irritable Bowel Syndrome With Constipation | Irritable Bowel Syndrome Characterized by Constipation | Irritable Bowel Syndrome Mixed | Irritable Bowel Syndrome Without Diarrhea | Irritable Bowel | Irritable Bowel Syndrome Aggravated and other conditionsUnited States
-
ClasadoCR2O B.V.RecruitingIrritable Bowel Syndrome | Irritable Bowel Syndrome - Constipation | Irritable Bowel Syndrome - Diarrhoea | Irritable Bowel Syndrome - MixedBelgium, Netherlands, United Kingdom
-
Istanbul Medipol University HospitalTepecik Training and Research Hospital; Bozyaka Training and Research Hospital and other collaboratorsRecruitingIrritable Bowel Syndrome | Irritable Bowel Syndrome With Diarrhea | Irritable Bowel Syndrome With Constipation | Irritable Bowel Syndrome MixedTurkey
-
Federal Stare Budgetary Scientific Institution,...I.M. Sechenov First Moscow State Medical University; RML INVEST, Torkhovsky...CompletedIrritable Bowel Syndrome | Irritable Bowel Syndrome With Diarrhea | Irritable Bowel Syndrome With Constipation | Irritable Bowel Syndrome MixedRussian Federation
-
University of California, Los AngelesCompletedIrritable Bowel Syndrome With Diarrhea | Irritable Bowel Syndrome With Mixed Bowel HabitsUnited States
-
University of ViennaCompleted
-
Thomayer University HospitalCharles University, Czech RepublicActive, not recruitingIrritable Bowel Syndrome With Diarrhea | Irritable Bowel Syndrome MixedCzechia
-
Shahid Beheshti University of Medical SciencesCompletedIrritable Bowel DiseaseIran, Islamic Republic of
-
Universidad Autonoma de ChihuahuaNot yet recruitingIrritable Bowel Syndrome | Constipation-predominant Irritable Bowel Syndrome | Diarrhea- Irritable Bowel Syndrome
-
Vasily IsakovRussian Science Foundation; Azbuka vkusa; Federal Research Centre of Nutrition...CompletedIrritable Bowel Syndrome With Constipation | Constipation-predominant Irritable Bowel SyndromeRussian Federation
Clinical Trials on Placebo
-
SamA Pharmaceutical Co., LtdUnknownAcute Bronchitis | Acute Upper Respiratory Tract InfectionKorea, Republic of
-
National Institute on Drug Abuse (NIDA)CompletedCannabis UseUnited States
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyCompletedMale Subjects With Type II Diabetes (T2DM)Germany
-
Heptares Therapeutics LimitedCompletedPharmacokinetics | Safety IssuesUnited Kingdom
-
GlaxoSmithKlineCompletedPulmonary Disease, Chronic ObstructiveUnited Kingdom, Netherlands
-
ItalfarmacoCompletedBecker Muscular DystrophyNetherlands, Italy
-
Shijiazhuang Yiling Pharmaceutical Co. LtdXuanwu Hospital, BeijingCompleted
-
GlaxoSmithKlineCompletedInfections, BacterialUnited States
-
West Penn Allegheny Health SystemCompletedAsthma | Allergic RhinitisUnited States