Protease Regulation and Impact of Sodium as Mechanisms of Inflammation in IBD

Not yet recruiting

• Conditions: Crohns Disease

• Registration Number: NCT07169123
• Lead Sponsor: McMaster University

Brief Summary

The study looks at how eating salt affects gut health in people with Crohn's disease. The aim of the study is to find out whether eating more salt increases the breakdown of proteins in the gut and if this makes inflammation and symptoms worse. By studying the link between salt, gut bacteria and inflammation, the study hopes to improve diet advice for people with Crohn's disease. This research may help find specific foods that affect the disease and lead to better, more personalized nutrition plans.

Detailed Description

This longitudinal exploratory study has two related phases:

Phase 1 will enroll 300 Crohn's disease (CD) patients from McMaster's IBD and IBD Nutrition Clinics to assess dietary sodium intake and fecal proteolytic activity in relation to disease activity (active/inactive). Participants will be followed annually for 2 years, forming a registry. At baseline and each follow-up visit, data collected will include: demographics, BMI, CDAI, diet (1-week food recall via Keenoa and 6-month sodium questionnaire), blood (sodium, metabolomics, CRP), stool (microbiota, metabolomics, fecal calprotectin, proteolytic activity), and spot urine (sodium, potassium, creatinine, metabolomics). Extra visits will occur if a disease flare happens.

Phase 2 will involve 80 participants from Phase 1 (40 high-sodium diet \[HSD\], 40 low-sodium diet \[LSD\]), selected based on sodium intake. Over three visits (baseline, week 1, week 2), participants will provide fecal samples for microbiota and metabolomics analysis, and blood/urine samples (baseline and week 2). Colonoscopy with biopsies and video will be performed at week 2. Diet will be closely tracked using Keenoa to assess intake of sodium, carbs, UPF, fibre, and calories. After Phase 2, participants return to Phase 1 follow-up.

Study Timeline

• Study First Submitted: 2025-06-05
• Status Verified: 2025-09
• Study First Submitted QC: 2025-09-05
• Last Update Submitted: 2025-09-05
• Study First Posted: 2025-09-11
• Last Update Posted: 2025-09-11
• Study Start: 2025-09-18
• Primary Completion: 2029-09-01
• Study Completion: 2029-09-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• 18 and 70 years of age
• Crohn's disease diagnosis
• Willing and able to sign written informed consent prior to study entry
• Able to comply with the study procedures, in the opinion of the investigator

Exclusion Criteria

• Antibiotics, antibacterial agents, or probiotics, currently, or within the last 8 weeks
• Alcohol or drug abuse
• Pregnancy
• Concurrent systemic disease and/or laboratory abnormalities considered by investigators to be a risk or that could interfere with data collection

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Dietary Sodium Intake	Phase 1: baseline (Year 0); Year 1; and Year 2. Phase 2: baseline (Week 0); Week 1; and Week 2.	Dietary sodium intake will be assessed via 24-hour dietary recall and sodium-specific food frequency questionnaires (mg/day). Values will be used to classify participants as HSD or LSD and correlated with changes in proteolytic activity, mucosal permeability, and disease activity.

Secondary Outcome Measures

Name	Time	Method
Proteolytic Activity in Stool and Colonic Biopsies	Stool: Phase 1 - baseline (Year 0); Year 1; and Year 2. Biopsy: Phase 2 - Week 2	Proteolytic activity will be assessed in fecal samples and colonic biopsies. Fecal samples will be analyzed for host and bacterial proteases (units of proteolytic activity per gram of stool, U/g), and colonic biopsies for host and bacterial proteases (units of proteolytic activity per mg of tissue, U/mg). Comparisons will be made between participants consuming a high-sodium diet (HSD) and a low-sodium diet (LSD) to evaluate associations with mucosal barrier dysfunction and disease activity over time.
Crohn's Disease Activity Index (CDAI)	Phase 1: baseline (Year 0); Year 1; and Year 2. Phase 2: baseline (Week 0); and Week 2.	Crohn's Disease Activity Index will be calculated using patient-reported symptoms, physical exam findings, and lab values (score, unitless). CDAI \<150 indicates remission, 150-220 mild disease, 220-450 moderate disease, and \>450 severe disease. CDAI scores will be compared between HSD and LSD groups to evaluate changes in clinical disease activity over time.
Mucosal Permeability	Phase 2: Week 2	Colonic biopsies will be analyzed for mucosal barrier integrity using permeability assays (e.g., FITC-dextran flux). Higher values indicate greater barrier dysfunction (permeability index, arbitrary units). Comparisons will be made between HSD and LSD groups to determine effects of dietary sodium intake.
Patient Subgroup Characterization Based on Metabolic and Microbial Profiles	Phase 1: baseline (Year 0); Year 1; and Year 2. Phase 2: baseline (Week 0); Week 1; and Week 2.	Participants will be characterized using dietary sodium intake, metabolic profiling (blood, urine, stool), and microbial activity (stool and biopsy-based proteolytic and microbiome analyses). Data will identify subgroups with distinct metabolic signatures, sodium intake levels, microbial profiles, and disease progression, providing insight into diet-microbiota-host metabolism interactions in Crohn's disease.

Trial Locations

Locations (1)

McMaster University Medical Centre; 🇨🇦 Hamilton, Ontario, Canada