Clinical Profiling of Anti-inflammatory Fibre Supplements in Patients With Ulcerative Colitis: Towards Personalized Complementary Strategies.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 69
- 试验地点
- 2
- 主要终点
- Changes in fecal calprotectin
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
The study is double-blinded. The fibre supplements are provided in individual daily sachets, packaged and code-labelled by researchers not involved in data analysis or patient care to ensure double-blinding.
入排标准
- 年龄范围
- 14 Years 至 60 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Known diagnosis of ulcerative colitis.
- •Evidence of active disease, defined as either 1) measured FCP >100 µg/g at screening, OR 2) Partial Mayo Scoring Index Assessment for UC ≥2 (adult patients) OR Pediatric UC Activity Index (PUCAI) ≥10 (pediatric patients). Patients who are in clinical remission (Partial Mayo <2 or PUCAI <10) that have active inflammation (elevated FCP >100 µg/g) would also be eligible, as will patients with active symptoms, regardless of availability of FCP.
- •Tanner stage ≥4 for pediatric patients.
- •Weight >40kg.
- •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 that use adequate contraceptive methods.
- •Able to maintain current lifestyle (diet, exercise, supplements/medications, and sleep) throughout study.
排除标准
- •Inability to provide informed consent.
- •Presence of Crohn disease, IBD unclassified, non-IBD bowel conditions (e.g., celiac), or motility disorder.
- •Presence of abnormal constrictions of the gastrointestinal tract, diseases of the esophagus and/or the superior opening of the stomach (cardia), potential or existing intestinal blockage, paralysis of the intestine, megacolon, fecal impaction, inflamed bowel or appendicitis, or have failed to defecate after taking another laxative.
- •History of significant chronic disorders such as severe cardiac disease, malignancy requiring systemic chemotherapy or radiation therapy, significant renal failure, severe pulmonary disease, kidney disorders, diabetes, arthritis, multiple sclerosis, or other immune-mediated conditions requiring systemic therapy.
- •Presence of serious infection (e.g., infectious colitis).
- •Presence of severe anemia, defined as hemoglobin <100 g/L or considered clinically significant based on physician discretion.
- •Presence of disease or condition that negatively impacts ability to swallow, which may interfere with intake of supplement.
- •Use of systemic antibiotics for more than a week during two months prior to intervention, or any antibiotic use during the intervention.
- •Use of medications that inhibit peristaltic movement (e.g. opioids, loperamide)
- •Consistent use of topical therapies (e.g., rectal suppositories, enemas) for at least a week, with a resulting improvement in symptoms (defined based on physician discretion).
- •Use of probiotic, prebiotic, or fibre supplements in month prior to intervention or during the course of the trial that are 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, stool softeners, or anti-diarrheal medications.
- •Chronic use of illicit drugs and/or excessive alcohol (e.g., average of >7 drinks/week).
- •Current smoker (cigarettes).
- •History of abdominal surgery, including appendectomy.
- •Pregnancy or intention of the patient to become pregnant during the study period.
- •Breastfeeding.
- •Allergy to any ingredients of investigational products or placebo (i.e., acacia gum, microcrystalline cellulose, or maltodextrin).
- •Unable to maintain high fiber intake through supplementation during intervention.
研究组 & 干预措施
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.
干预措施: Acacia Gum (Dietary Supplement)
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.
干预措施: Microcrystalline Cellulose (Dietary Supplement)
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.
干预措施: Placebo (Dietary Supplement)
结局指标
主要结局
Changes in fecal calprotectin
时间窗: Week 3 and Week 6 (and week 12, if applicable)
Calprotectin will be analyzed in fecal samples. Clinically-relevant reductions are defined as levels \<100 µg/g or reduced by at least 50% from baseline.
次要结局
- Changes in disease activity(Week 3 and Week 6 (and week 12, if applicable))
- Changes in fecal dry mass percentage(Week 3 and Week 6 (and week 12, if applicable))
- Changes in gut barrier function: plasma lipopolysaccharide binding protein(Week 3 and Week 6 (and week 12, if applicable))
- Changes in fecal pH(Week 3 and Week 6 (and week 12, if applicable))
- Changes in gastrointestinal symptoms(Week 3 and Week 6 (and week 12, if applicable))
- Need for rescue therapy(Week 3 and Week 6 (and week 12, if applicable))
- Changes in fecal bile acids(Week 3 and Week 6 (and week 12, if applicable))
- Changes in routine clinical bloodwork(Week 3 and Week 6 (and week 12, if applicable))
- Changes in patient quality of life(Week 3 and Week 6 (and week 12, if applicable))
- Changes in fecal microbiome composition(Week 3 and Week 6 (and week 12, if applicable))
- Changes in fecal short-chain fatty acids(Week 3 and Week 6 (and week 12, if applicable))
- Changes in the plasma inflammatory cytokines(Week 3 and Week 6 (and week 12, if applicable))
- Changes in dietary intake(Week 3 and Week 6 (and week 12, if applicable))
- Changes in function of the fecal microbiome(Week 3 and Week 6 (and week 12, if applicable))
- Changes in gut barrier function: fecal zonulin(Week 3 and Week 6 (and week 12, if applicable))
- Changes in the plasma metabolome(Week 3 and Week 6 (and week 12, if applicable))
- Changes in body weight(Week 3 and Week 6 (and week 12, if applicable))