Personalized Anti-Inflammatory Fibres in Ulcerative Colitis (PAIF-UC)

Clinical Profiling of Anti-inflammatory Fibre Supplements in Patients With Ulcerative Colitis: Towards Personalized Complementary Strategies.

The goal of this clinical trial is to determine the clinical effects of two different dietary fibre supplements, acacia gum (AG) and microcrystalline cellulose (MCC), in patients with ulcerative colitis. The main question it aims to answer is: Can the fibre supplements reduce gut inflammation (fecal calprotectin)?

Researchers will compare AG and MCC to a placebo (a look-alike substance that contains no fibre) to see if the fibre supplements improve inflammation in ulcerative colitis.

Participants will add their assigned fibre supplement or placebo to their usual diet daily for 6 weeks. They will visit the clinic at baseline, week 3, and week 6 to provide samples (stool, blood) and complete various questionnaires.

Study Overview

• Status: Recruiting
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Dietary supplement: Acacia Gum; Dietary supplement: Microcrystalline Cellulose; Dietary supplement: Placebo

Detailed Description

Prevalence and incidence of inflammatory bowel diseases (IBD), including ulcerative colitis (UC), is rising rapidly in Canada and the rates are amongst the highest globally (Crohn's and Colitis Canada, 2023). UC is a chronic disease characterized by colonic inflammation, often inadequately managed in the long-term with immunosuppressive medications that can increase risk of infections and malignancies (Kayal & Shah, 2019). Alternative, complementary strategies are, therefore, necessary to improve patient outcomes.

A potential target for such strategies may be the gut microbiome, which can predict failure of standard therapy in pediatric UC (Michail et al., 2012). Putative, pro-inflammatory microbes are enriched in patients with IBD compared to healthy controls and disease phenotypes can be transferred via microbiome transplantation into germ-free mice (Nagao-Kitamoto et al., 2016; Birtton et al., 2019), suggesting a causal role of the gut microbiome in IBD. Fibre-based treatments for UC have been proposed and tested for UC but results are mixed, quite modest in many cases, and many gaps remain in defining the most appropriate clinical approach (Di Rosa et al., 2022; Limketkai et al, 2020).

Dietary fibre has great potential as a safe, complementary, microbiome-targeted treatment strategy to reduce inflammation in UC. Food supplementation with fermentable fibres alters microbiome composition (So et al., 2018) and increases microbial production of bioactive metabolites like short-chain fatty acids (SCFAs) that can attenuate inflammation (Parada Venegas et al., 2019; Levine et al., 2018). Provision of growth substrates in the form of fibre also enhances gut barrier function by decreasing mucus degradation, thus reducing bacterial encroachment and immune activation that may drive inflammation (Desai et al., 2016; Earle et al., 2015). However, specific fibre structures elicit distinct health effects due to differences in physicochemical properties (Gill et al., 2020). Therefore, important open questions remain, such as which fibres and physicochemical properties are most beneficial in the context of UC, and are their effects microbiome-dependent?

Hypothesis: Acacia gum (AG; soluble and fermentable fibre) and microcrystalline cellulose (MCC; insoluble and non-fermentable fibre) will decrease gut inflammation in patients with UC, but through different mechanisms given their differences in fermentability.

The overall goal of this study is to determine the clinical effects of AG and MCC in patients with UC, using normalization of FCP as the primary outcome.

Voluntary trial extension: Participants in whom the primary outcome has been achieved at week 6 will be invited to participate in an optional (completely voluntary) extension of the trial and continue their assigned treatment for an additional six weeks. This will allow for exploratory assessment of longer-term efficacy of the fibres (primary and secondary outcomes assessed again at week 12). Apart from the planned study, if a clinical decision is made by the patient and physician to perform sigmoidoscopy or colonoscopy (which is justified in many cases), bio samples and data from these procedures will be collected if patients agree. The procedure will not be a research procedure, but the patients will be approached and consented for bio sample collection. The optional extension will advantageously provide further biological insights into the effects of the fibres and can inform future intervention studies.

• Study Type: Interventional
• Enrollment (Estimated): 69
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Eytan Wine, MD, PhD; Phone Number: (780) 248-5494; Email: wine@ualberta.ca
• Study Contact Backup: Name: Anissa Armet, PhD, RD; Email: aarmet@ualberta.ca

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2X8
      • Recruiting
      • University of Alberta Hospital
      • Contact: Anissa Armet, PhD, RD; Email: aarmet@ualberta.ca
      • Contact: Eytan Wine, MD, PhD; Phone Number: 780-492-2223; Email: wine@ualberta.ca
      • Principal Investigator: Eytan Wine, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Known diagnosis of ulcerative colitis.
• Measured fecal calprotectin of >250 µg/g at screening.
• Mild disease: Partial Mayo Scoring Index Assessment for UC between 0-4 (adult patients).
• Mild disease: Pediatric UC Activity Index (PUCAI) between 0-34 (pediatric patients).
• Tanner stage 5 for pediatric patients.
• Weight >50kg.
• No changes to IBD-related medications in three months prior to study onset (stable therapy, including use of 5-aminosalicylic acid, biologics, and immunosuppressive medications; some minor adjustments allowed, such as increasing dose for weight change, or change to a compatible/generic treatment).
• Men and women; the latter must be menstruating and using contraceptives.

Exclusion Criteria:

• Inability to provide informed consent.
• Presence of Crohn disease, IBD unclassified, non-IBD bowel conditions (e.g., celiac), or motility disorder.
• Use of systemic antibiotics for more than a week during two months prior to intervention, or any antibiotic use during the intervention.
• Use of probiotic, prebiotic, or fibre supplements in month prior to intervention known to affect the gut microbiome (if these are present in foods, such as yogurt or fermented foods, this will be allowed).
• Chronic use of laxatives or stool softeners.
• History of abdominal surgery, including appendectomy.
• Pregnancy or intention of the patient to become pregnant during the study period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acacia Gum; Acacia gum is a dietary fibre with low-viscosity and is fermentable. Female participants consume 12.5 grams each day for the first two days of the intervention, then consume 25 grams each day for the rest of the six-week intervention. Male participants consume 17.5 grams each day for the first two days of the intervention, then consume 35 grams each day for the rest of the six-week intervention. Those participants who voluntarily extend their treatment for an additional six weeks will continue with consuming the full dose daily.	Dietary supplement: Acacia Gum; Participants (n=23) incorporate the fibre supplement into their usual diet daily.; Other Names: AGRI-SPRAY ACACIA® R, Agrigum International
Experimental: Microcrystalline Cellulose; Microcrystalline cellulose is a dietary fibre that is non-viscous and and non-fermentable. Female participants consume 12.5 grams each day for the first two days of the intervention, then consume 25 grams each day for the rest of the six-week intervention. Male participants consume 17.5 grams each day for the first two days of the intervention, then consume 35 grams each day for the rest of the six-week intervention. Those participants who voluntarily extend their treatment for an additional six weeks will continue with consuming the full dose daily.	Dietary supplement: Microcrystalline Cellulose; Participants (n=23) incorporate the fibre supplement into their usual diet daily.; Other Names: MICROCEL® MC-12, ROQUETTE
Placebo Comparator: Maltodextrin; Maltodextrin is a digestible carbohydrate. It is provided in isocaloric doses to the dietary fibres. Female participants consume 6.3 grams each day for the first two days of the intervention, then consume 12.5 grams each day for the rest of the six-week intervention. Male participants consume 8.8 grams each day for the first two days of the intervention, then consume 17.5 grams each day for the rest of the six-week intervention.	Dietary supplement: Placebo; Participants (n=23) incorporate the placebo into their usual diet daily.; Other Names: GLUCIDEX® IT 19 - MALTODEXTRIN, ROQUETTE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in fecal calprotectin	Calprotectin will be analyzed in fecal samples. Clinically-relevant reductions are defined as levels <150 µg/g or reduced by at least 50% from baseline.	Week 3 and Week 6 (and week 12, if applicable)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in disease activity	Scores obtained from either the Partial Mayo Scoring Index Assessment for adult participants or the Pediatric Ulcerative Colitis Activity Index for pediatric participants.	Week 3 and Week 6 (and week 12, if applicable)
Changes in fecal microbiome composition	Fecal microbiome composition will be analyzed using whole metagenome sequencing to measure changes at different taxonomic levels (e.g. genus, species).	Week 3 and Week 6 (and week 12, if applicable)
Changes in function of the fecal microbiome	Fecal microbiome functions will be analyzed using whole metagenome sequencing to measure changes in enzymes and pathways encoded by gut microbiota.	Week 3 and Week 6 (and week 12, if applicable)
Changes in gut barrier function: fecal zonulin	Fecal samples will be analyzed for changes in zonulin (ng/mg).	Week 3 and Week 6 (and week 12, if applicable)
Changes in gut barrier function: plasma lipopolysaccharide binding protein	Plasma from blood samples will be analyzed for changes in lipopolysaccharide binding protein (µg/mL).	Week 3 and Week 6 (and week 12, if applicable)
Changes in fecal short-chain fatty acids	Short-chain fatty acids (acetate, propionate, butyrate, valerate) and branched-chain fatty acids (isovalerate, isobutyrate) will be measured in fecal samples using gas chromatography mass spectrometry (µmol/g).	Week 3 and Week 6 (and week 12, if applicable)
Changes in fecal bile acids	Bile acid derivatives will be measured in fecal samples using ultrahigh performance liquid chromatography/multiple-reaction monitoring-mass spectrometry (nmol/g).	Week 3 and Week 6 (and week 12, if applicable)
Changes in fecal pH	Fecal pH will be measured using a pH meter.	Week 3 and Week 6 (and week 12, if applicable)
Changes in fecal dry mass percentage	Fecal moisture content, or percentage of dry mass, will be measured by drying fecal material overnight in an oven.	Week 3 and Week 6 (and week 12, if applicable)
Changes in the plasma metabolome	Untargeted metabolomics will be applied to plasma samples via high performance chemical isotope labeling liquid chromatography mass spectrometry platform.	Week 3 and Week 6 (and week 12, if applicable)
Changes in the plasma inflammatory cytokines	Several inflammatory cytokines (e.g., TNF-α, IL-6) will be analyzed in plasma samples using multiplex, electrochemiluminescence assays.	Week 3 and Week 6 (and week 12, if applicable)
Changes in routine clinical bloodwork	Routine clinical bloodwork will be performed for patients (e.g., C-reactive protein, liver enzymes, albumin, etc.)	Week 3 and Week 6 (and week 12, if applicable)
Changes in body weight	Body weight will be measured in kilograms and will be used to calculate body mass index.	Week 3 and Week 6 (and week 12, if applicable)
Changes in gastrointestinal symptoms	Individual gastrointestinal symptoms will be measured by a gastrointestinal symptom questionnaire (scored on a scale of 0-5; higher scores indicating more symptoms).	Week 3 and Week 6 (and week 12, if applicable)
Changes in dietary intake	Dietary intake will be measured by 24 hour dietary recalls (using ASA-24).	Week 3 and Week 6 (and week 12, if applicable)
Changes in patient quality of life	Patient quality of life will be evaluated using the EQ-5D-5L questionnaire.	Week 3 and Week 6 (and week 12, if applicable)
Need for rescue therapy	Changes to patient therapy regimes (e.g., steroids, dose escalation), inability to complete the study, and adverse events related to the intervention will be monitored and analyzed.	Week 3 and Week 6 (and week 12, if applicable)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biopsies, Brushings, Intestinal Washes, and Endoscopy Scores	In those participants who voluntarily extend their treatment for an additional six weeks, if a clinical decision is made by the patient and physician to perform sigmoidoscopy or colonoscopy, biosamples (biopsies, brushing, and intestinal washes) and data (endoscopy scores) will be collected from these procedures if patients agree. The procedure will not be a research procedure, but the patients will be approached and consented for biosample collection.	Week 12

Collaborators and Investigators

• Sponsor: University of Alberta
• Collaborators: Weston Family Foundation
• Investigators: Principal Investigator: Eytan Wine, MD, PhD, University of Alberta

Publications and helpful links

General Publications

• Desai MS, Seekatz AM, Koropatkin NM, Kamada N, Hickey CA, Wolter M, Pudlo NA, Kitamoto S, Terrapon N, Muller A, Young VB, Henrissat B, Wilmes P, Stappenbeck TS, Nunez G, Martens EC. A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility. Cell. 2016 Nov 17;167(5):1339-1353.e21. doi: 10.1016/j.cell.2016.10.043.
• Michail S, Durbin M, Turner D, Griffiths AM, Mack DR, Hyams J, Leleiko N, Kenche H, Stolfi A, Wine E. Alterations in the gut microbiome of children with severe ulcerative colitis. Inflamm Bowel Dis. 2012 Oct;18(10):1799-808. doi: 10.1002/ibd.22860. Epub 2011 Dec 14.
• Levine A, Sigall Boneh R, Wine E. Evolving role of diet in the pathogenesis and treatment of inflammatory bowel diseases. Gut. 2018 Sep;67(9):1726-1738. doi: 10.1136/gutjnl-2017-315866. Epub 2018 May 18.
• So D, Whelan K, Rossi M, Morrison M, Holtmann G, Kelly JT, Shanahan ER, Staudacher HM, Campbell KL. Dietary fiber intervention on gut microbiota composition in healthy adults: a systematic review and meta-analysis. Am J Clin Nutr. 2018 Jun 1;107(6):965-983. doi: 10.1093/ajcn/nqy041.
• Gill SK, Rossi M, Bajka B, Whelan K. Dietary fibre in gastrointestinal health and disease. Nat Rev Gastroenterol Hepatol. 2021 Feb;18(2):101-116. doi: 10.1038/s41575-020-00375-4. Epub 2020 Nov 18.
• Crohn's and Colitis Canada. Impact of inflammatory bowel disease in Canada. Available from: https://crohnsandcolitisca/About-Us/Resources-Publications/Impact-of-IBD-Report2023.
• Kayal M, Shah S. Ulcerative Colitis: Current and Emerging Treatment Strategies. J Clin Med. 2019 Dec 30;9(1):94. doi: 10.3390/jcm9010094.
• Nagao-Kitamoto H, Shreiner AB, Gillilland MG 3rd, Kitamoto S, Ishii C, Hirayama A, Kuffa P, El-Zaatari M, Grasberger H, Seekatz AM, Higgins PD, Young VB, Fukuda S, Kao JY, Kamada N. Functional Characterization of Inflammatory Bowel Disease-Associated Gut Dysbiosis in Gnotobiotic Mice. Cell Mol Gastroenterol Hepatol. 2016 Mar 3;2(4):468-481. doi: 10.1016/j.jcmgh.2016.02.003. eCollection 2016 Jul.
• Britton GJ, Contijoch EJ, Mogno I, Vennaro OH, Llewellyn SR, Ng R, Li Z, Mortha A, Merad M, Das A, Gevers D, McGovern DPB, Singh N, Braun J, Jacobs JP, Clemente JC, Grinspan A, Sands BE, Colombel JF, Dubinsky MC, Faith JJ. Microbiotas from Humans with Inflammatory Bowel Disease Alter the Balance of Gut Th17 and RORgammat+ Regulatory T Cells and Exacerbate Colitis in Mice. Immunity. 2019 Jan 15;50(1):212-224.e4. doi: 10.1016/j.immuni.2018.12.015.
• Di Rosa C, Altomare A, Imperia E, Spiezia C, Khazrai YM, Guarino MPL. The Role of Dietary Fibers in the Management of IBD Symptoms. Nutrients. 2022 Nov 11;14(22):4775. doi: 10.3390/nu14224775.
• Limketkai BN, Gordon M, Mutlu EA, De Silva PS, Lewis JD. Diet Therapy for Inflammatory Bowel Diseases: A Call to the Dining Table. Inflamm Bowel Dis. 2020 Mar 4;26(4):510-514. doi: 10.1093/ibd/izz297.
• Earle KA, Billings G, Sigal M, Lichtman JS, Hansson GC, Elias JE, Amieva MR, Huang KC, Sonnenburg JL. Quantitative Imaging of Gut Microbiota Spatial Organization. Cell Host Microbe. 2015 Oct 14;18(4):478-88. doi: 10.1016/j.chom.2015.09.002. Epub 2015 Oct 1.
• Parada Venegas D, De la Fuente MK, Landskron G, Gonzalez MJ, Quera R, Dijkstra G, Harmsen HJM, Faber KN, Hermoso MA. Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases. Front Immunol. 2019 Mar 11;10:277. doi: 10.3389/fimmu.2019.00277. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: July 10, 2024
• First Submitted That Met QC Criteria: July 16, 2024
• First Posted (Actual): July 23, 2024

Study Record Updates

• Last Update Posted (Actual): June 10, 2025
• Last Update Submitted That Met QC Criteria: June 5, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: gut microbiome; ulcerative colitis; inflammatory bowel disease; dietary fibre
• Additional Relevant MeSH Terms: Pathologic Processes; Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Colitis; Colitis, Ulcerative; Ulcer
• Other Study ID Numbers: Pro00137948

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data will be shared that underlies the results reported after deidentification (text, tables, figures, and appendices). Data will be made available through a safe and secure publicly available data sharing repository.
• IPD Sharing Time Frame: Immediately following publication, ending 5 years following publication.
• IPD Sharing Access Criteria: Anyone who wishes to access the data may do so to achieve aims in the approved proposal and for individual participant data meta-analysis.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

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