Randomised clinical trial: high-dose oral thiamine versus placebo for chronic fatigue in patients with quiescent inflammatory bowel disease

Background Fatigue is a burdensome symptom for patients with inflammatory bowel disease (IBD). Few pharmacological interventions have documented effect on fatigue in patients with IBD. A pilot study indicated a 20-day effect with high-dose thiamine. Aims To investigate the effect and safety of high-dose oral thiamine (600-1800 mg/d) based on gender and weight on chronic fatigue in patients with quiescent IBD. Methods This was a randomised, double-blinded, placebo-controlled crossover trial. Patients had quiescent IBD, severe chronic fatigue and no other explanation for fatigue. Patients were allocated 1:1 to either 1) high-dose oral thiamine for 4 weeks, 4 weeks of washout, 4 weeks of oral placebo or 2) oral placebo for 4 weeks, 4 weeks of washout, 4 weeks of high-dose oral thiamine. Fatigue was measured using the Inflammatory Bowel Disease-Fatigue Questionnaire. The primary outcome was improvement (>= 3 points) of fatigue after 4 weeks on thiamine. Results Forty patients were enrolled between November 2018 and October 2019. Crossover analysis showed a mean reduction of 4.5 points (95% CI 2.6-6.2) in fatigue after thiamine compared with a mean increase of 0.75 point (95% CI -1.3-2.8; P = 0.0003) after placebo. Furthermore, 55% of group 1 and 75% of group 2 showed an improvement >= 3 points while on thiamine compared with 25% of group 1 and 35% of group 2 while on placebo. Only mild side effects were detected. Conclusion We showed a significant beneficial effect of high-dose oral thiamine on chronic fatigue in IBD. The treatment was well tolerated. Trial registration: NCT03634735.

Automated summary

The study demonstrated a significant beneficial effect of high-dose oral thiamine on chronic fatigue in patients with IBD, with good tolerability and symptom improvement. Results from the trial indicated that thiamine was effective in reducing fatigue levels compared to placebo, showing promising outcomes for managing fatigue in IBD patients.