Ulcerative Colitis (UC)
Conditions
Keywords
Ulcerative colitis
Brief summary
This study aims to test whether a short liquid-based diet, followed by a low-sulfur eating plan, is safe, manageable, and helpful for people with mild to moderate ulcerative colitis. Investigators want to see if this approach can improve gut health, lower inflammation, and reduce symptoms. Investigators will also test breath samples as an easy, non-invasive way to track gut bacteria activity and disease changes. Investigators believe this diet plan can reduce harmful gut bacteria that produce irritating sulfur compounds, leading to better gut health and measurable improvements that can be detected through breath testing.
Detailed description
Purpose To determine whether a short-term elemental diet followed by a reduced sulfur diet is a safe, tolerable, and effective non-pharmacologic strategy to improve clinical outcomes, reduce inflammation, and beneficially modulate the gut microbiome in adults with mild-to-moderate ulcerative colitis. A secondary purpose is to validate breath-based biomarkers as non-invasive tools to monitor sulfur metabolism and disease activity. Breath biomarkers include volatile organic compounds (VOCs) and exhaled breath condensate (EBC) to assess sulfur-related metabolites. Hypothesis A 2-week elemental diet followed by a 10-week reduced sulfur diet will reduce intestinal inflammation and improve clinical outcomes by shifting the gut microbiome away from pro-inflammatory, sulfur-metabolizing bacteria, resulting in reduced sulfur metabolite production detectable through exhaled volatile organic compounds and exhaled breath condensate. Justification Despite advances in biologic therapies, many UC patients fail to achieve sustained remission, and current treatments do not address upstream drivers such as diet-microbiome interactions. Elemental diets have demonstrated efficacy in Crohn's disease but remain understudied in UC. Emerging evidence links dietary sulfur, microbial sulfur metabolism, and toxic metabolites to UC pathogenesis. This study addresses critical gaps by testing a feasible dietary intervention and validating non-invasive breath biomarkers for real-time disease monitoring and precision nutrition. Objectives * Evaluate the clinical efficacy, safety, and feasibility of an elemental diet followed by an reduced sulfur diet. * Characterize changes in gut microbiome composition, inflammatory markers, and sulfur-related metabolic outputs. * Validate breath-based volatile organic compounds and exhaled breath condensate as biomarkers of sulfur metabolism and treatment response. * Identify microbial and metabolic signatures predictive of dietary response. Research Design A prospective, randomized, controlled trial in adults with mild-to-moderate UC. All participants complete a 2-week elemental diet, followed by randomization (2:1) to either a reduced sulfur diet group (intervention group) or return to habitual diet group (control group) for 10 weeks. Clinical indices, inflammatory biomarkers, stool microbiome profiles and breath samples are collected longitudinally. The initial 2-week elemental diet is applied uniformly to standardize baseline microbial and metabolic conditions prior to randomization and does not replace or delay clinical care decisions. Statistical Analysis Primary outcomes will be assessed using within- and between-group comparisons of clinical and biochemical response at week 12. Microbiome and metabolomic data will be analyzed using multivariate and differential abundance methods. Correlations between breath biomarkers, microbiome features, and clinical outcomes will assess sensitivity and specificity.
Interventions
DIETARY_SUPPLEMENTElemental formula (mBiota Elemental, Good LFE, Santa Monica, CA)
Elemental liquid diets (EDs) are a subset of Exclusive Enteral Nutrition (EEN). Similar to EEN, they are nutritionally complete formulas, but differ in that they consist of free amino acids, monosaccharides, and fatty acids instead of whole, intact macronutrients, which are designed for optimal digestibility and to minimize antigenicity. EDs have been shown to reduce immune activation, favourably modulate the microbiota, suppress proinflammatory cytokines, support epithelial repair, and exclude common dietary additives that may provoke inflammation.
BEHAVIORALReduced Sulfur diet
This diet excludes high sulfur foods (e.g., red meat, seafood, eggs), cruciferous vegetables, dried fruits, and fermented beverages. It also accounts for sulfate intake from drinking water and processed food additives.
BEHAVIORALHabitual Diet
Participants randomized to the comparator group will continue their usual dietary intake for 10 weeks without specific dietary restrictions.
Sponsors
University of British Columbia
University of Calgary
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
19 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Age 19-70 years. =Diagnosis of mild-to-moderate ulcerative colitis, defined by a partial Mayo score (pMayo) of 2-7. * Evidence of active inflammation at enrollment, defined as: * C-reactive protein (CRP) \> 5 mg/L; or * Fecal calprotectin (FCP) \> 200 µg/g. * Receiving stable medical therapy for ulcerative colitis for at least 8 weeks prior to enrollment. * No corticosteroid use at the time of recruitment. * Under consideration by the treating physician for treatment escalation or biologic switch due to inadequate response to current therapy.
Exclusion criteria
* Partial Mayo score (pMayo) \> 7. * Pregnant or breastfeeding. * Body mass index (BMI) \< 18 kg/m². * History of an eating disorder. * Severe psychiatric disorder. * Severe medical conditions, including: * Active cancer; * Significant cardiovascular disease; * Diabetes mellitus; or * Severe food allergies. * Known allergy or intolerance to corn, dextrose, or maltodextrin. * Antibiotic use within 3 months prior to enrollment. * Probiotic use within 3 months prior to enrollment. * Use of herbal anti-inflammatory supplements during the study period, including but not limited to: * Serrapeptidase; * Curcumin; * Boswellia; or * Bromelain. * History of major gastrointestinal surgery, including: * Ostomy; * Total colectomy; or * Short bowel syndrome. * Inability or unwillingness to comply with study procedures, including anticipated travel or other commitments that may interfere with participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite clinical and biochemical response | Baseline, Week 2 and week 12 | Composite clinical and biochemical response at week 12, defined as \>30% and \>1-point reduction in pMayo score from baseline, plus rectal bleeding subscore decrease of \>1 or an absolute subscore \<1, with fecal calprotectin \<250 μg/g and CRP \<5 mg/L. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stool Biomarkers | Baseline, week 2 and week 12 | fecal calprotectin, shotgun metagenomics (microbiome composition, sulfur metabolizing bacteria), and targeted metabolomics (e.g., hydrogen sulfide, thiosulfate) |
| C-Reactive Protein (CRP) concentration | Baseline, week 2 and week 12 | Serum CRP concentration will be measured to assess systemic inflammation. |
| Complete Blood Count (CBC) parameters | Baseline, week 2 and week 12 | CBC parameters, including hemoglobin, white blood cell count, platelet count, and differential counts, will be measured. |
| Serum inflammatory biomarker concentrations | Baseline, week 2 and week 12 | Serum concentrations of IL-6, TNF-α, MCP-1, and LBP will be measured individually and reported separately. |
| Breath Biomarkers | Baseline, week 2 and week 12 | Volatile Organic Compounds (VOCs) and exhaled breath condensate (EBC) to assess sulfur-containing metabolites and host-microbiota interactions |
| Adherence to the Elemental Diet and Reduced Sulfur Diet Intervention | Baseline, week 2 and week 12 | Adherence to the ED intervention will be assessed using a modified Medication Adherence Report Scale questionnaire at each visit, as well as through compliance phone calls and food diaries. Poor adherence will be defined as meeting at least one of the following three criteria: 1. intolerance, indicated by discontinuation of dietary therapy due to the patient's refusal to continue; or 2. low adherence scores (score of 0-1) reported on the modified Medication Adherence Report Scale; and 3. collect the empty mBiota containers as a measure of adherence. Adherence to the RS diet will be assessed through food recalls collected via ASA-24. Adverse events (AEs) will be systematically collected throughout the study using a combination of participant self-reporting, scheduled assessments, and clinical monitoring. |
| Change in Quality of Life | Baseline, week 2 and week 12 | Health-related quality of life will be measured using the 12-item short form-12 (SF-12). The SF-12 comprises two components: physical health and mental health. Scores range from 0 to 100, where 0 indicates the lowest level of health and 100 the highest. |
| Change in Anxiety | Baseline, week 2 and week 12 | Anxiety will be assessed by the GAD-7 (Generalized Anxiety Disorder-7). It is a self-reported screening tool used to measure the severity of generalized anxiety disorder (GAD) symptoms over the past two weeks. The total score ranges from 0 to 21. A score of 10 or higher typically indicates clinically significant anxiety and suggests the need for further evaluation or intervention.. |
| Change in Depression | Baseline, week 2 and week 12 | Depression levels will be assessed by PHQ-8 (Patient Health Questionnaire-8). It is a widely used self-report screening tool for assessing the severity of depressive symptoms over the past two weeks. The total score is the sum of all item responses, ranging from 0 to 24. A score of 10 or higher indicates the presence of clinically significant depressive symptoms and suggests the need for further evaluation or intervention. |
| Change in Weight | Baseline, week 2 and week 12 | Body weight will be measured in kilograms (kg) |
| Change in Body Mass Index (BMI) | Baseline, week 2 and week 12 | BMI will be calculated as weight (kg) divided by height squared (m²). |
Countries
Canada
Contacts
CONTACTNatasha Haskey, PhD
PRINCIPAL_INVESTIGATORNatasha Haskey, RD, PhD
University of British Columbia
Outcome results
None listed