Hydrogen peroxide pathway in ulcerative colitis: Promises and challenges in translating novel pathogenesis to clinical practice

Table 2 Phase 2 randomized controlled trial design for mild to moderate active ulcerative colitis

Design requirements	Specific protocol	Key considerations
Study design	Multicenter, randomized, double-blind, placebo-controlled phase 2 trial	Compliance with ICH-GCP standards
Target population	Patients with mild to moderate active UC (PRO2 score 2-5 points)	Balance baseline risk; standardize severity assessment
Inclusion criteria	Age 18-65 yr; MES score 1-2 points; discontinue biologics ≥ 8 wk	Exclude severe UC and active infectious diseases
Sample size	180 subjects (90 per group)	80% statistical power; anticipated 15% dropout rate[23]
Randomization design	1:1 randomized allocation by disease severity stratification	Ensure balanced baseline characteristics and reduce bias
Treatment groups	Group A: 5-ASA + STS (extracellular H2O2 scavenger); Group B: 5-ASA + placebo	Specific dosing regimens determined through phase 1 dose-escalation studies
Biomarker assessments	Weeks 0, 4, 8, 12: CRP, fecal calprotectin, neutrophil count, serum 8-isoprostane F2α, malondialdehyde, GPx activity	Based on STRIDE-II criteria[24]; combined oxidative stress biomarkers
Primary endpoint	Clinical response rate at week 12 (PRO2 score reduction ≥ 50%)	Meets STRIDE-II recommended patient-reported outcome measures
Key secondary endpoints	Clinical remission, endoscopic response, histological improvement, oxidative stress biomarker changes at week 12	Endoscopic response: MES ≤ 1 point; Histological improvement: Geboes score < 2.0
Safety assessment	Liver and kidney function tests at Weeks 0, 4, 8, 12; document and evaluate adverse events at each visit	Balance safety monitoring requirements with patient convenience
Follow-up plan	Treatment period: 12 wk + long-term follow-up to 52 wk	Evaluate long-term efficacy maintenance and safety

UC: Ulcerative colitis; ICH-GCP: International Council for Harmonisation-Good Clinical Practice; MES: Mayo Endoscopic Score; PRO2: Patient-Reported Outcome 2; 5-ASA: 5-aminosalicylic acid; GPx: Glutathione peroxidase; STRIDE-II: Selecting Therapeutic Targets in Inflammatory Bowel Disease Initiative update; CRP: C-reactive protein.