Clinical trial NCT03803319: Effects of Dietary Fibre in Irritable Bowel Syndrome (IBS)
Official title: Microbiological and Physiological Effects of Dietary Supplementation With Fibre in Irritable Bowel Syndrome: a Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Irritable Bowel Syndrome
Keywords: dietary fibre
Lead sponsor: King's College London
Sponsor class: OTHER
Collaborators: name: Guy's and St Thomas' NHS Foundation Trust
name: Universidad Veracruzana
name: University of Liverpool
First posted: 2019-01-14
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: multi-centre, 3 treatment, placebo-controlled trial
Primary purpose: TREATMENT

Brief summary: The aim of the study is to investigate how different dietary fibre combinations affects physiological and microbiological outcomes, in addition to symptoms in those with IBS. The study will also explore the differences in responses between different fibres in different sub-types of IBS (e.g. constipation-predominant, diarrhoea-predominant and mixed).

Detailed description: Currently, national and international guidelines are based upon trials of dietary fibre in IBS symptoms that report opposing effects. For this reason, recommendations regarding dietary fibre food supplementation in IBS are often conflicting. Indeed, the confusion surrounding dietary fibre recommendations in IBS is a consequence of the limited understanding of the different types of dietary fibres used, their physiology and their functions in different sub-groups of IBS.

Different fibres have different characteristics (e.g. solubility, viscosity and fermentability) which drive different functionalities (stool forming, fermentation) in the gastrointestinal tract, yet it is currently unknown whether administration of dietary fibre combinations will result in symptomatic improvement in people with IBS.

Participants will be randomised to one of three parallel arms for a duration of 8 weeks.

The study will consist of 4 visits in total. The first visit will involve taking consent and assessing eligibility. Participants will complete the Rome IV diagnostic criteria as part of their eligibility assessment. Participants will be asked to complete a food and symptom diary for the next 7 days. Diary data will be used to confirm frequency and severity of IBS symptoms and ensure there is no discrepancy between participant report on the Rome IV diagnostic criteria.

Visit 2: Baseline (approx 1.5 hours). Height and weight will be recorded. Participants will complete 7 questionnaires, provide a stool sample, a blood sample and will ingest the SmartPill (wireless motility capsule). Participants will blinded to the intervention and will be provided with sachets containing either fibre 1 (combined fibres), fibre 2 (natural fibres) or placebo to consume over an 8-week period.

Visit 3: Mid-point (approx 1 hour). Participants will complete 5 questionnaires and provide a stool sample.

Visit 4: Endpoint (approx 1.5 hours). Height and weight will be recorded. Participants will complete 7 questionnaires, provide a stool sample, a blood sample and will ingest the SmartPill (wireless motility capsule).

Eligibility criteria: Inclusion Criteria:

* Interested in taking part
* Ability to give informed consent
* Men and women aged 18-65 years with diarrhoea-predominant IBS (IBS-D), constipation-dominant IBS (IBS-C), or mixed (IBS-M), based on fulfilment of the Rome IV criteria for irritable bowel syndrome who do not have a major medical condition (e.g. diabetes, psychiatric or current eating disorders), severe oesophagitis, gastritis or duodenitis, gastrointestinal disease (inflammatory bowel disease, coeliac disease, active diverticulitis), or history of previous GI surgery (excluding appendicectomy, cholecystectomy and haemorrhoidectomy), severe renal, cardiac, pulmonary, or other chronic diseases likely to affect motility, history of gastric bezoars.

Exclusion Criteria:

* Females who report to be pregnant or lactating
* Body Mass Index (BMI) \>40 kg/m2
* Use of unpermitted medications in the last 4 weeks prior to, or during the study including: Antibiotics within the last 4weeks, dietary fibre food supplements within the last 4 weeks (e.g. Fybogel, Lactulose), prebiotics or probiotics (in food products or as supplements) within the last 4 weeks, other dietary supplements that may affect the luminal microenvironment of the intestine (e.g. Orlistat)
* Use of drugs known to alter GI motility, transit or gastric pH (e.g. mebeverine, opiates, monoamine oxidase inhibitors, phenothiazines) in the last 1 week
* Full bowel preparation for a diagnostic procedure within the last 4 weeks
* Changes to IBS medications or dose in the 4 weeks prior to the study
* Changes to anti-depressant medications or dose in the 12 weeks prior to the study
* Swallowing disorders (physical or psychological)
* Use of implantable and/or medical devices such as pacemakers
* Individuals following extreme diets e.g. 8 or more caffeinated serves per day, 4 or more bottles of wine (40 or more units of alcohol per week) or equivalent per week as assessed by diet questionnaires or changes to smoking habits
* Individuals who have participated in other intervention trials within 3 months prior to screening
* Allergies to components (soy) of the SmartBar (required for SmartPill protocol)
* Abdominal pain for less than 2 days in the screening week (based on the GSRS mild to severe)
* Those who report adequate relief of symptoms at baseline using the GSQ

Primary outcomes:
measure: Relative abundance of faecal bifidobacteria as assessed using 16S rRNA community profiling (Illumina Miseq) of bacterial genomic DNA isolated from stool samples
timeFrame: 0, 4, 8 weeks
measure: IBS symptoms as assessed using the Global Symptom Question (GSQ)
timeFrame: 0, 4, 8 weeks
Secondary outcomes:
measure: Whole gut and regional gut transit time as assessed using a telemetric device (wireless motility capsule: SmartPill)
timeFrame: 0 and 8 weeks
measure: Colonic pH units as assessed using a telemetric device (wireless motility capsule: SmartPill)
timeFrame: 0 and 8 weeks
measure: Pressure (mmHg) as assessed using a telemetric device (wireless motility capsule: SmartPill)
timeFrame: 0 and 8 weeks
measure: Faecal short-chain fatty acids (SCFAs) as assessed using gas-liquid chromatography
timeFrame: 0, 4, 8 weeks
measure: Faecal gut microbiota (α and β diversity) as assessed using 16S rRNA community profiling (Illumina Miseq) of bacterial genomic DNA isolated from stool samples
timeFrame: 0, 4, 8 weeks
measure: Faecal volatile organic compounds (VOCs) as assessed using gas chromatography sensor device
timeFrame: 0 and 8 weeks
measure: Serum/plasma appetite hormones (ghrelin, pg/ml) as determined by enzyme-linked immunosorbent assay (ELISA)
timeFrame: 0 and 8 weeks
measure: Serum/plasma (leptin, pg/ml) as determined by enzyme-linked immunosorbent assay (ELISA)
timeFrame: 0 and 8 weeks
measure: Serum/plasma metabolites as determined using metabolomics
timeFrame: 0 and 8 weeks
measure: Stool consistency as assessed using the Bristol Stool Form Scale (BSFS) (7 point scale; Type 1 to Type 7)
timeFrame: 0 and 8 weeks
measure: Gastrointestinal symptoms as assessed using the Gastrointestinal Symptom Rating Scale (GSRS) over 7 days (absent - severe)
timeFrame: 0 and 8 weeks
measure: Gastrointestinal symptoms as assessed using the Irritable Bowel Syndrome Symptom Severity Scale (IBS-SSS) (visual analogue scale: no pain - severe)
timeFrame: 0, 4, 8 weeks
measure: Quality of Life (QoL) general as assessed using the SF-36
timeFrame: 0, 4, 8 weeks
measure: Disease-specific QoL as assessed using the IBS-QoL (5 point scale: not at all - a great deal)
timeFrame: 0, 4, 8 weeks
measure: Perceived stress as assessed using the Perceived Stress Score (PSS) (5 point scale: never- very often)
timeFrame: 0, 4, 8 weeks
measure: Dietary fibre acceptability as assessed using an acceptability questionnaire (5 point scale: not at all acceptable - extremely acceptable)
timeFrame: 8 weeks
measure: Nutrient intake as assessed using a 7-day food diary
timeFrame: 0 and 8 weeks
measure: Physical activity as assessed using the International Physical Activity Questionnaire (IPAQ)
timeFrame: 0 weeks
measure: Waist circumference as assessed using a standard measuring tape (inches)
timeFrame: 0 and 8 weeks
measure: Hydrogen/methane breath testing as assessed using the Gastrocheck Gastrolyzer V9.0 in parts per million
timeFrame: 0 and 8 weeks
Other outcomes:
measure: Visceral sensitivity as assessed using the Visceral Sensitivity Index (VSI) (6 point scale: strongly agree - strongly disagree)
timeFrame: 0 and 8 weeks
Locations:
city: London
country: United Kingdom
facility: King's College London
Study officials:
affiliation: King's College London
name: Kevin C Whelan, PhD
role: STUDY_DIRECTOR
References: