Effect of Modified Cellulose on Colonic Fermentation of Inulin (COCOA2)

Effect of Modified Cellulose on Colonic Fermentation of Inulin (COCOA2)

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.

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome
• Intervention / Treatment: Dietary supplement: Psyllium; Dietary supplement: Maltodextrin; Dietary supplement: Methylcellulose

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

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
      • University Hospital Clinical Research Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Psyllium; Psyllium 15 g+ inulin 15 gm in 375ml water	Dietary supplement: Psyllium; 15g psyllium added to inulin solution to form a gel
Placebo Comparator: maltodextrin; Maltodextrin 15 g + inulin 15 gm in 375 ml water	Dietary supplement: Maltodextrin; 15g maltodextrin added to inulin solution to form a gel
Experimental: Methylcellulose; Methylcellulose 15g + Inulin 15 g in 375 ml water	Dietary supplement: Methylcellulose; 15 g methylcellulose added to inulin solution to form a gel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Breath hydrogen	AUC 0-6 hours after ingestion	0-6 hoursafter ingestion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Breath hydrogen	AUC 0-24 hours	0-24 hours post ingestion
Breath methane	AUC 0-24 hours	0-24 hours post ingestion
Transit time	whole gut transit time	Whole gut transit measured once before intervention

Collaborators and Investigators

• Sponsor: University of Nottingham
• Collaborators: University of East Anglia
• Investigators: Principal Investigator: Robin D Spiller, MD, University of Nottingham

Publications and helpful links

General Publications

• 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): May 9, 2023
• Primary Completion (Actual): August 31, 2023
• Study Completion (Actual): August 31, 2023

Study Registration Dates

• First Submitted: June 9, 2023
• First Submitted That Met QC Criteria: June 9, 2023
• First Posted (Actual): June 22, 2023

Study Record Updates

• Last Update Posted (Actual): August 15, 2024
• Last Update Submitted That Met QC Criteria: August 12, 2024
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: FODMAP; Inulin; Psyllium; Cellulose
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Irritable Bowel Syndrome; Gastrointestinal Agents; Cathartics; Psyllium
• Other Study ID Numbers: FMHS 19-0622

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No