Effects of Dietary Fibre in Irritable Bowel Syndrome (IBS)

• ClinicalTrials.gov Identifier: NCT03803319
• Recruitment Status: Completed
• First Posted: January 14, 2019
• Last Update Posted: February 6, 2020
• Sponsor: King's College London
• Collaborators: Guy's and St Thomas' NHS Foundation Trust; Universidad Veracruzana; University of Liverpool
• Information provided by (Responsible Party): King's College London

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Irritable Bowel Syndrome	Dietary Supplement: Fibre 1 (combined fibres); Dietary Supplement: Fibre 2 (natural fibres); Dietary Supplement: Dietary Supplement: placebo	Not Applicable

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 135 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: multi-centre, 3 treatment, placebo-controlled trial
• Masking: Double (Participant, Investigator)
• Masking Description: Participants and Investigators will be blinded to the fibre provided over the 8-week intervention period.
• Primary Purpose: Treatment
• Official Title: Microbiological and Physiological Effects of Dietary Supplementation With Fibre in Irritable Bowel Syndrome: a Randomised Controlled Trial
• Actual Study Start Date: January 2, 2019
• Actual Primary Completion Date: January 11, 2020
• Actual Study Completion Date: January 11, 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Fibre 1 (combined fibres); Ingestion of 150mls water with 7.5g fibre (two times a day)	Dietary Supplement: Fibre 1 (combined fibres); Dietary fibre supplement
Active Comparator: Fibre 2 (natural fibres); Ingestion of 150mls water with 15g fibre (two times a day)	Dietary Supplement: Fibre 2 (natural fibres); Dietary fibre supplement
Placebo Comparator: Dietary Supplement (placebo); Ingestion of 150mls water with 7.5g (two times a day)	Dietary Supplement: Dietary Supplement: placebo; Dietary supplement

Outcome Measures

Primary Outcome Measures :

1. Relative abundance of faecal bifidobacteria as assessed using 16S rRNA community profiling (Illumina Miseq) of bacterial genomic DNA isolated from stool samples [ Time Frame: 0, 4, 8 weeks ]
   Change from baseline in relative abundance of bifidobacteria between the three groups at 8 weeks
2. IBS symptoms as assessed using the Global Symptom Question (GSQ) [ Time Frame: 0, 4, 8 weeks ]
   Change from baseline in the GSQ between the three groups at 8 weeks

Secondary Outcome Measures :

1. Whole gut and regional gut transit time as assessed using a telemetric device (wireless motility capsule: SmartPill) [ Time Frame: 0 and 8 weeks ]
   Change from baseline in whole and regional gut transit time between the three groups at 8 weeks
2. Colonic pH units as assessed using a telemetric device (wireless motility capsule: SmartPill) [ Time Frame: 0 and 8 weeks ]
   Change from baseline in colonic pH units between the three groups at 8 weeks
3. Pressure (mmHg) as assessed using a telemetric device (wireless motility capsule: SmartPill) [ Time Frame: 0 and 8 weeks ]
   Change from baseline in pressure (mmHg) between the three groups at 8 weeks
4. Faecal short-chain fatty acids (SCFAs) as assessed using gas-liquid chromatography [ Time Frame: 0, 4, 8 weeks ]
   Change from baseline in microbial metabolites between the three groups at 8 weeks
5. Faecal gut microbiota (α and β diversity) as assessed using 16S rRNA community profiling (Illumina Miseq) of bacterial genomic DNA isolated from stool samples [ Time Frame: 0, 4, 8 weeks ]
   Change from baseline in faecal gut microbiota (α and β diversity) between the three groups at 8 weeks
6. Faecal volatile organic compounds (VOCs) as assessed using gas chromatography sensor device [ Time Frame: 0 and 8 weeks ]
   Change from baseline in VOCs between the three groups at 8 weeks
7. Serum/plasma appetite hormones (ghrelin, pg/ml) as determined by enzyme-linked immunosorbent assay (ELISA) [ Time Frame: 0 and 8 weeks ]
   Change from baseline in ghrelin concentrations between the three groups at 8 weeks
8. Serum/plasma (leptin, pg/ml) as determined by enzyme-linked immunosorbent assay (ELISA) [ Time Frame: 0 and 8 weeks ]
   Change from baseline in leptin concentrations between the three groups at 8 weeks
9. Serum/plasma metabolites as determined using metabolomics [ Time Frame: 0 and 8 weeks ]
   Change from baseline in plasma/serum metabolites between the three groups at 8 weeks
10. Stool consistency as assessed using the Bristol Stool Form Scale (BSFS) (7 point scale; Type 1 to Type 7) [ Time Frame: 0 and 8 weeks ]
    Change from baseline in stool consistency and stool frequency between the three groups at 8 weeks
11. Gastrointestinal symptoms as assessed using the Gastrointestinal Symptom Rating Scale (GSRS) over 7 days (absent - severe) [ Time Frame: 0 and 8 weeks ]
    Change from baseline in gastrointestinal symptoms between the three groups at 8 weeks
12. Gastrointestinal symptoms as assessed using the Irritable Bowel Syndrome Symptom Severity Scale (IBS-SSS) (visual analogue scale: no pain - severe) [ Time Frame: 0, 4, 8 weeks ]
    Change from baseline in the severity of gastrointestinal symptoms between the three groups at 8 weeks
13. Quality of Life (QoL) general as assessed using the SF-36 [ Time Frame: 0, 4, 8 weeks ]
    Change from baseline in general QoL between the three groups at 8 weeks
14. Disease-specific QoL as assessed using the IBS-QoL (5 point scale: not at all - a great deal) [ Time Frame: 0, 4, 8 weeks ]
    Change from baseline in disease-specific QoL between the three groups at 8 weeks
15. Perceived stress as assessed using the Perceived Stress Score (PSS) (5 point scale: never- very often) [ Time Frame: 0, 4, 8 weeks ]
    Change from baseline in perceived stress between the three groups at 8 weeks
16. Dietary fibre acceptability as assessed using an acceptability questionnaire (5 point scale: not at all acceptable - extremely acceptable) [ Time Frame: 8 weeks ]
    Dietary fibre acceptability between the three groups at 8 weeks
17. Nutrient intake as assessed using a 7-day food diary [ Time Frame: 0 and 8 weeks ]
    7-day food diary
18. Physical activity as assessed using the International Physical Activity Questionnaire (IPAQ) [ Time Frame: 0 weeks ]
    Physical activity
19. Waist circumference as assessed using a standard measuring tape (inches) [ Time Frame: 0 and 8 weeks ]
    Change from baseline in waist circumference between the three groups at 8 weeks
20. Hydrogen/methane breath testing as assessed using the Gastrocheck Gastrolyzer V9.0 in parts per million [ Time Frame: 0 and 8 weeks ]
    Hydrogen/methane breath testing

Other Outcome Measures:

1. Visceral sensitivity as assessed using the Visceral Sensitivity Index (VSI) (6 point scale: strongly agree - strongly disagree) [ Time Frame: 0 and 8 weeks ]
   Change from baseline in visceral sensitivity between the three groups at 8 weeks

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United Kingdom

King's College London

London, United Kingdom, SE1 9NH

Sponsors and Collaborators

King's College London

Guy's and St Thomas' NHS Foundation Trust

Universidad Veracruzana

University of Liverpool

Investigators

• Study Director: Kevin C Whelan, PhD; King's College London

More Information

• Responsible Party: King's College London
• ClinicalTrials.gov Identifier: NCT03803319
• Other Study ID Numbers: 18/WA/0313
• First Posted: January 14, 2019
• Last Update Posted: February 6, 2020
• Last Verified: January 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Participant information will only be available to the Investigators undertaking the study.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by King's College London:

dietary fibre

Additional relevant MeSH terms:

Irritable Bowel Syndrome; Syndrome; Disease; Pathologic Processes; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases