Clinical trial NCT05911347: Effect of Modified Cellulose on Colonic Fermentation of Inulin
Official title: Effect of Modified Cellulose on Colonic Fermentation of Inulin (COCOA2)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Irritable Bowel Syndrome
Keywords: FODMAP
Inulin
Psyllium
Cellulose
Lead sponsor: University of Nottingham
Sponsor class: OTHER
Collaborators: name: University of East Anglia
First posted: 2023-06-22
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 3 way cross-over
Primary purpose: BASIC_SCIENCE

Brief summary: A 3-way randomised cross-over study to test the hypothesis that combining either psyllium or methylcellulose to form a gel incorporating inulin will reduce gas production as compared to inulin given with a placebo, maltodextrin. Subjects will attend on 3 separate days separated by a minimum of one week an consume one of 3 test meals. Serial breath samples with be obtained to measure hydrogen and methane over the next 24 hours. Primary endpoint: Area under curve (AUC) from time 0-6 hours (AUC 0-6) of breath hydrogen (ppm.hour) after treatment intake. The investigators will also assess whole gut transit time using the blue muffin and correlate breath hydrogen production with in vitro fermentation results.

Detailed description: A 3-way randomised cross-over study to test the hypothesis that combining either psyllium or methylcellulose to form a gel incorporating inulin will reduce gas production as compared to inulin given with a placebo, maltodextrin. Subjects will attend on 3 separate days separated by a minimum of one week an consume one of 3 test meals. Serial breath samples with be obtained to measure hydrogen and methane over the next 24 hours.

Primary endpoint: Area under curve (AUC) from time 0-6 hours (AUC 0-6) of breath hydrogen (ppm.hour) after treatment intake. Whole gut transit time will be assessed from the time that stool turns blue after ingestion of a muffin labelled with blue food colouring.

Secondary endpoint:

1. AUC (0-24h) breath hydrogen / methane
2. Oro-cecal transit time and whole gut transit time.
3. Gas production/ metabolites/ microbiota during in vitro fermentation studies at Quadram
4. Effect of habitual dietary FODMAPs intake on breath hydrogen response to inulin.

The interventions will be dietary interventions, using all food grade materials (sugars and fibres) provided in commonly used doses:

Breath hydrogen will be correlated with in vitro carbohydrate fermentation profile assessed using stool samples collected before intervention

Eligibility criteria: Inclusion Criteria:

* Aged 18 or older.
* Able to give informed consent.
* Scoring ≤5 (i.e., mild, or less) for symptoms of flatulence, bloating, abdominal pain, loose stool, and hard stool in previous 2 weeks using a modified Gastrointestinal Symptom Rating Scale (5).
* Agrees to consume the meals provided.
* Agrees to not smoke during the breath sampling period.

Exclusion Criteria:

* Pregnancy declared by candidate.
* History declared by the candidate of pre-existing gastrointestinal disorder that may affect bowel function.
* Reported history of previous resection of the oesophagus, stomach, or intestine (excluding appendix).
* Intestinal stoma.
* Any medical condition making participation potentially compromising participation in the study e.g., diabetes mellitus, respiratory disease limiting ability to use breath hydrogen analyser, known intolerance to one of the test substances.
* Will not agree to dietary restrictions required.
* Unable to stop drugs known to alter GI motility including mebeverine, opiates, monoamine oxidase inhibitors, phenothiazines, benzodiazepines, calcium channel antagonists for the duration of the study (Selective serotonin reuptake inhibitors, low dose tricyclic antidepressants, antihistamines, and oral contraceptive pill will be recorded in the CRF but will not be an exclusion criteria).
* Participants who are taking antibiotics or probiotics as it might alters gut microbiota.
* Poor understanding of English language.
* Participation in night shift work the week prior to the study day. Night work is defined as working between midnight and 6.00 AM.
* Anyone who in the opinion of the investigator is unlikely to be able to comply with the protocol e.g., cognitive dysfunction, chaotic lifestyle related to substance abuse.
* Having taken part in a research study in the last 3 months involving invasive procedures or an inconvenience allowance.

Primary outcomes:
measure: Breath hydrogen
timeFrame: 0-6 hoursafter ingestion
Secondary outcomes:
measure: Breath hydrogen
timeFrame: 0-24 hours post ingestion
measure: Breath methane
timeFrame: 0-24 hours post ingestion
measure: Transit time
timeFrame: Whole gut transit measured once before intervention
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: University Hospital Clinical Research Centre
state: Nottinghamshire
Study officials:
affiliation: University of Nottingham
name: Robin D Spiller, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.