A home-based exercise programme attenuates fatigue in primary biliary cholangitis: Results from the EXCITED clinical trial

JHEP Rep. 2024 Sep 6;6(12):101210. doi: 10.1016/j.jhepr.2024.101210. eCollection 2024 Dec.

Abstract

Background & aims: Fatigue 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).

Methods: A 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]).

Results: A 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.

Conclusion: This 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 implications: Fatigue 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.

Keywords: Autoimmune Liver Disease; Cholestasis; Functional Capacity; Health Related Quality of Life; Patient Reported Outcome Measure; Symptoms.

Associated data

  • ClinicalTrials.gov/NCT04265235