High-dose oral thiamine versus placebo for chronic fatigue in patients with primary biliary cholangitis: A crossover randomized clinical trial.

Abstract

Background & aimsFatigue has high negative impact on many patients with primary biliary cholangitis (PBC) and treatment options are limited. Recently we showed favorable effects of four weeks of high-dose thiamine treatment on fatigue in patients with inflammatory bowel disease. We aimed to investigate the effect and safety of high-dose (600-1800 mg daily) oral thiamine treatment on chronic fatigue in patients with PBC.MethodsRandomized, double-blinded, placebo-controlled crossover trial including patients with severe PBC-related fatigue. Participants were allocated 1:1 to either group 1) 4 weeks of high-dose thiamine, 4 weeks of washout, and 4 weeks of placebo; or group 2) 4 weeks of placebo, washout, and high-dose thiamine, respectively. Fatigue severity was quantified using the fatigue subscale of the PBC-40 questionnaire. The primary outcome was a fatigue reduction of ≥ 5 points after 4 weeks of high-dose thiamine treatment.ResultsWe enrolled 36 patients; 34 completed the study. The overall mean reduction in fatigue was 5.0 points (95% CI: 2.5 to 7.5; p ConclusionFour weeks of high-dose oral thiamine treatment in patients with PBC was well tolerated and safe. However, high-dose thiamine was not superior to placebo in reducing PBC-related fatigue.Trial registrationThe trial was registered in the ClinicalTrials.gov (NCT04893993) and EudraCT (2020-004935-26).