Clinical trial NCT06515210: Personalized Anti-Inflammatory Fibres in Ulcerative Colitis
Official title: Clinical Profiling of Anti-inflammatory Fibre Supplements in Patients With Ulcerative Colitis: Towards Personalized Complementary Strategies.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Ulcerative Colitis
Keywords: inflammatory bowel disease
ulcerative colitis
dietary fibre
gut microbiome
Lead sponsor: University of Alberta
Sponsor class: OTHER
Collaborators: name: Weston Family Foundation
First posted: 2024-07-23
Enrollment: 69
Sex: ALL
Minimum age (years): 15
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blinded, parallel-arm, placebo-controlled, six-week clinical trial, with optional 6-week extension for participants in whom the primary outcome is achieved.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Changes in fecal calprotectin
timeFrame: Week 3 and Week 6 (and week 12, if applicable)
Secondary outcomes:
measure: Changes in disease activity
timeFrame: Week 3 and Week 6 (and week 12, if applicable)
measure: Changes in fecal microbiome composition
timeFrame: Week 3 and Week 6 (and week 12, if applicable)
measure: Changes in function of the fecal microbiome
timeFrame: Week 3 and Week 6 (and week 12, if applicable)
measure: Changes in gut barrier function: fecal zonulin
timeFrame: Week 3 and Week 6 (and week 12, if applicable)
measure: Changes in gut barrier function: plasma lipopolysaccharide binding protein
timeFrame: Week 3 and Week 6 (and week 12, if applicable)
measure: Changes in fecal short-chain fatty acids
timeFrame: Week 3 and Week 6 (and week 12, if applicable)
measure: Changes in fecal bile acids
timeFrame: Week 3 and Week 6 (and week 12, if applicable)
measure: Changes in fecal pH
timeFrame: Week 3 and Week 6 (and week 12, if applicable)
measure: Changes in fecal dry mass percentage
timeFrame: Week 3 and Week 6 (and week 12, if applicable)
measure: Changes in the plasma metabolome
timeFrame: Week 3 and Week 6 (and week 12, if applicable)
measure: Changes in the plasma inflammatory cytokines
timeFrame: Week 3 and Week 6 (and week 12, if applicable)
measure: Changes in routine clinical bloodwork
timeFrame: Week 3 and Week 6 (and week 12, if applicable)
measure: Changes in body weight
timeFrame: Week 3 and Week 6 (and week 12, if applicable)
measure: Changes in gastrointestinal symptoms
timeFrame: Week 3 and Week 6 (and week 12, if applicable)
measure: Changes in dietary intake
timeFrame: Week 3 and Week 6 (and week 12, if applicable)
measure: Changes in patient quality of life
timeFrame: Week 3 and Week 6 (and week 12, if applicable)
measure: Need for rescue therapy
timeFrame: Week 3 and Week 6 (and week 12, if applicable)
Other outcomes:
measure: Biopsies, Brushings, Intestinal Washes, and Endoscopy Scores
timeFrame: Week 12
Locations:
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
Study officials:
affiliation: University of Alberta
name: Eytan Wine, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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