Dataset Information

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

ABSTRACT:

Background & aims

Fatigue 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.

Methods

Randomized, 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.

Results

We 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 < 0.001) for the combined group 1 and group 2. Crossover analysis showed a mean increase in fatigue of 0.3 points (95% CI: -4.2 to 3.8) after high-dose thiamine treatment compared to a 1.4 points (95% CI: 6.2 to -3.4) mean reduction after placebo (p = 0.55). Only mild and transient adverse events were recorded.

Conclusion

Four 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 registration

The trial was registered in the ClinicalTrials.gov (NCT04893993) and EudraCT (2020-004935-26).

SUBMITTER: Bager P

PROVIDER: S-EPMC10980237 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Bager Palle P Bossen Lars L Gantzel Rasmus R Grønbæk Henning H

PloS one 20240329 3

<h4>Background & aims</h4>Fatigue 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.<h4>Methods</h4>Randomized, double-blinded, placebo-controlled cross ...[more]

PMID: 38551983

Similar Datasets

Project description:Purpose of reviewPrimary biliary cholangitis (PBC) is characterized by autoimmune damage of intrahepatic bile ducts associated with a loss of tolerance to mitochondrial antigens. PBC etiopathogenesis is intriguing because of different perplexing features, namely: a) although mitochondria are present in all cell types and tissues, the damage is mainly restricted to biliary epithelial cells (BECs); b) despite being an autoimmune disorder, it does not respond to immunosuppressive drugs but rather to ursodeoxycholic acid, a bile salt that induces HCO3- rich choleresis; c) the overwhelming female preponderance of the disease remains unexplained. Here we present an etiopathogenic view of PBC which sheds light on these puzzling facts of the disease.Recent findingsPBC develops in patients with genetic predisposition to autoimmunity in whom epigenetic mechanisms silence the Cl-/HCO3- exchanger AE2 in both cholangiocytes and lymphoid cells. Defective AE2 function can produce BECs damage as a result of decreased biliary HCO3- secretion with disruption of the protective alkaline umbrella that normally prevents the penetration of toxic apolar bile salts into cholangiocytes. AE2 dysfunction also causes increased intracellular pH (pHi) in cholangiocytes, leading to the activation of soluble adenylyl cyclase, which sensitizes BECs to bile salt-induced apoptosis. Recently, mitophagy was found to be inhibited by cytosolic alkalization and stimulated by acidification. Accordingly, we propose that AE2 deficiency may disturb mitophagy in BECs, thus, promoting the accumulation of defective mitochondria, oxidative stress and presentation of mitochondrial antigens to the immune cells. As women possess a more acidic endolysosomal milieu than men, mitophagy might be more affected in women in an AE2-defective background. Apart from affecting BECs function, AE2 downregulation in lymphocytes may also contribute to alter immunoregulation facilitating autoreactive T-cell responses.SummaryPBC can be considered as a disorder of Cl-/HCO3- exchange in individuals with genetic predisposition to autoimmunity.

Project description:Background & aimsFatigue is a commonly reported symptom of primary biliary cholangitis (PBC). We conducted a single-arm, open-label clinical trial to assess the efficacy of a physiotherapist-led home-based exercise programme (HBEP) in patients with PBC and moderate-to-severe fatigue (NCT04265235).MethodsA 12-week individualised HBEP (aerobic + resistance based) was delivered to patients with a PBC-40 fatigue domain score ≥33. The primary efficacy outcome measure was a reduction in fatigue severity by ≥5 points. Secondary outcome measures included other domains of PBC-40, the FIS (fatigue impact scale), ESS (Epworth sleepiness score), HADS (hospital anxiety and depression scale), aerobic capacity (ISWT [incremental shuttle walk test], Duke activity status index (predicted VO₂ peak) and physical function (short physical performance battery [SPPB]).ResultsA total of 31 patients were recruited, of whom 30 completed the 12-week HBEP (29 women; median age 53 years, median alkaline phosphatase value: 1.5x the upper limit of normal, median bilirubin: 12 μmol/L, and median baseline PBC-40 fatigue score 42). The primary outcome was met by 26 patients, with a median reduction in PBC-40 fatigue score of -10.5 points (IQR -9 to -13; p <0.001). Reductions were also observed in the symptom, cognition, and emotion domains of PBC-40, and in the FIS, ESS and HADS (p <0.01 for all measures). This was alongside increases in the median ISWT (+90 m; IQR 57.5-110), predicted VO₂ peak (+2.41 ml/kg/min; IQR 0.01-4.05), and SPPB (+1 point; IQR 0-1.4) (all p <0.001). 28 participants achieved the maximum SPPB score of 12/12 (vs. 13 patients at baseline; p <0.001). No significant adverse events were reported.ConclusionThis proof-of-concept study shows that a HBEP is safe, feasible, and has the potential to attenuate fatigue. Controlled trials are needed to validate the efficacy of exercise interventions in PBC.Impact and implicationsFatigue is a common symptom in primary biliary cholangitis (PBC), and is linked to cognitive dysfunction, somnolence, and reduced activity. The pathogenesis is multifactorial, and muscle bioenergetic abnormalities have been proposed to contribute. In this study, we show that a home-based exercise programme, consisting of aerobic and resistance-based sets, can be safely delivered to people living with PBC. In addition, the programme led to a reduction in fatigue severity, less daytime sleepiness and improved cognitive function.

Dataset Information

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

Background & aims

Methods

Results

Conclusion

Trial registration

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets