Effect of Methylcellulose or Psyllium on Fermentation of inUlin Assessed USing MRI (RUFUS)

Randomised Placebo Controlled Trial of Methylcellulose or Psyllium on Fermentation of inUlin Assessed USing MRI (RUFUS)

Our challenge is to understand how fibre interacts with whole-gut function to alter colonic fermentation of FODMAPs. We will exploit the recent availability of a range of food grade modified celluloses which can form gels at body temperature to perform human studies to explore whether the beneficial effect of psyllium is unique or will be found with all gelling substances (4). We are currently performing the COCOA2 study using a modified methylcellulose (results awaited). We now wish to perform a pilot study to image what happens in the colon when methylcellulose is ingested to enable us to plan the next step in our research programme.

Study Overview

• Status: Recruiting
• Conditions: Colon, Irritable
• Intervention / Treatment: Dietary supplement: Psyllium; Dietary supplement: Inulin; Dietary supplement: Methylcellulose; Dietary supplement: Maltodextrin

Detailed Description

Aim Our aim is to pilot the next study which will test the hypothesis that a gel of either methylcellulose or psyllium incorporating inulin will reduce colonic gas volumes assessed by MRI 0-6 hours and 24 hours post ingestion as compared to inulin combined with placebo, maltodextrin.

Objective The primary objective of this pilot is to find the minimum dose which will clearly show the effect of methylcellulose and /or psyllium on colonic gas as assessed by MRI. Previous studies have used large doses to ensure a large effect to avoid a type II error however the doses used are well outside the normal consumption. We wish to compare the effect of our methylcellulose mix on the fermentation of 10 and 15 g of inulin by offering different doses of fibre gel drink.,

Secondary Objectives A) Assess the effect of methylcellulose on gastric emptying, OCTT by MRI assessment of arrival of "head of meal", regional MRI colonic appearances, including signal intensity at 6 and 24 hours to determine the likely length of effect, C) to asses breath hydrogen production over 24 hour post ingestion including overnight assessments, D) to assess Whole Gut Transit Time (WGTT) using blue muffins test, E) to measure AUC (0-24) for breath methane; F) to measure gas production over 48 hours incubation in vitro model of colon (in collaboration with Quadram Institute); G) to measure metabolite production (short chain fatty acids) using in vitro model of colon(in collaboration with Quadram Institute); H) to analyse microbiota using 16sRNA gene (in collaboration with Quadram Institute); I) to assess the effect of habitual dietary FODMAPs intake on breath hydrogen response to inulin.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Robin Spiller; Phone Number: +447824328319; Email: robin.spiller@nottingham.ac.uk

Study Locations

• United Kingdom
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
      • Recruiting
      • Nottingham Digestive Disease Centre
      • Contact: Alaa Alhasani, BSc; Phone Number: 01159429924; Email: alyaa11@exmail.nottingham.ac.uk
      • Contact: Robin Spiller; Phone Number: +447824328319; Email: robin.spiller@nottingham.ac.uk

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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 hydrogen sampling period.

Exclusion Criteria:

• • Pregnancy, lactating, or planning pregnancy during the course of the investigation 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.
  • Have contraindications for MRI scanning i.e. metallic implants, pacemakers, history of metallic foreign body in eye(s) and penetrating eye injury.
  • Unable to lie flat and relatively still for less than 5 minutes.
  • 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.
  • Has a body mass index (BMI) value less than 18.5 or greater than 35.
  • Will not agree to follow dietary and lifestyle 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: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Psyllium; 375 ml containing 15g inulin made up in 375 ml water with 15 g psyllium husk	Dietary supplement: Psyllium; 15 g psyllium + 15 g inulin; Dietary supplement: Inulin; 15 inulin
Experimental: Methylcelulose; 375 ml containing 15g inulin made up in 375 ml water with 15g modified methylcellulose	Dietary supplement: Inulin; 15 inulin; Dietary supplement: Methylcellulose; 15 g methylcellulose + 15 g inulin
Placebo Comparator: Maltodextrin; 375 ml containing 15g inulin made up in 375 ml water with maltodextrin powder (placebo)	Dietary supplement: Inulin; 15 inulin; Dietary supplement: Maltodextrin; 15 maltodextrin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
colonic gas volume	AUC 0-6 hours of colonic gas volume	0-6 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
colonic gas volume at 6 hours	MRI assessed colonic gas volume at 6 hours	0-6 hours
Breath hydrogen	Area under curve (AUC) from time 0-6 hours of breath hydrogen (ppm.hours)	0-6 hours
Oro-cecal transit time		0- 6 hours
24 hour breath hydrogen	Area under curve (AUC) from time 0-24 hours of breath hydrogen (ppm.hours)	0-24 hours

Collaborators and Investigators

• Sponsor: University of Nottingham
• Collaborators: Quadram Institute Bioscience

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2023
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): October 30, 2024

Study Registration Dates

• First Submitted: February 26, 2024
• First Submitted That Met QC Criteria: February 26, 2024
• First Posted (Estimated): March 4, 2024

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• 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 328-0723

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