Multimodal prehabilitation: The multimodal prehabilitation program will consist of:
1. twice-weekly supervised exercise training at the hospital gym for approximately 8 weeks (induction phase), followed by 16 weeks of telematic, supervised, home-based exercise (maintenance phase);
2. nutritional consultation, including diet optimization and supplementation if needed;
3. individual or group-based psychological support.
standard of care: Participants in the control group will follow the standard of care provided by the hospital and will receive general recommendations on physical activity, nutrition, and stress/anxiety management.
Study summary
The implementation of a non-pharmacological multimodal intervention program-including physical exercise, nutritional counseling, and psychological support-is expected to improve fatigue in patients with primary biliary cholangitis. Consequently, this improvement is anticipated to enhance quality of life and cognitive symptoms, while also positively impacting emotional, social, and occupational aspects.
From a pathophysiological perspective, it is hypothesized that chronic cholestasis and/or immune system activation, with the release of pro-inflammatory cytokines, leads to both central and peripheral alterations causing fatigue.
At the central level, systemic inflammation may induce neuronal senescence in the basal ganglia, resulting in altered functional connectivity networks dependent on these regions and/or structural and connectivity changes in areas involved in interoception, such as the insula and anterior cingulate cortex.
At the peripheral level, the hypothesis is that chronic inflammation mediated by anti-mitochondrial antibodies causes mitochondrial metabolic dysfunction in muscle cells, which would be reflected in changes observed in the gene expression analysis of these cells.
Improvement in fatigue following the multimodal intervention program is expected to be associated with normalization of the immunological profile, enhanced functional brain connectivity, and improved mitochondrial metabolism in muscle.
Eligibility
Sex
ALL
Min age
18 Years
Max age
80 Years
Healthy volunteers
Accepted
Inclusion Criteria:
* Age ≥18 years
* PBC diagnosis according to EASL guidelines
* Moderate - severe fatigue defined by ≥ 29 points in PBC-40 questionnaire
Exclusion Criteria:
* Age \> 80 years
* Severe pruritus
* Decompensated cirrhosis
* Other causes of liver disease than PBC
* Liver transplant (LT) o placement on a waiting-list for LT
* Uncontrolled thyroid disesase
* Anemia with haemoglobin \<11g/dl
* Uncontrolled cardiovascular risk factors
* BMI \> 35,
* Acute myocardial infarct or unstable angina the past 6 months
* Muscle disease or systemic disease with potential muscle involvement
* Dysautonomy
* Untreated osteoporosis
* Untreated celiac disease
* Alcohol consumption \> 14 standard drinks (SD) in women and \>21 (SD) in men per week
* Chronic kidney disease ≥ 4 KDIGO stage
* Malignancy in the past two years (except for non melanoma skin cancer and in situ cervical carcinoma)
* Not capable of performing or following the prehabilitation program
* Involvement in a clinical trial the previous 2 months
* Refusal of informed consent
For the study of the pathophysiology of fatigue, additional exclusion criteria will be established: Severe depression or neuropsychiatric disease, 2) Treatment with centrally acting drugs, 3) Muscular or systemic disease with potential muscle involvement, 4) Immunosuppressive treatment, 5) Sleep disorder, 6) Obesity (BMI \>30).
Primary outcome measure(s)
Change in Fatigue Severity Assessed by PBC-40 — Baseline (week 0), post-intervention (week 8), and end of maintenance phase (6 months). To evaluate the effect of a non-pharmacological multimodal intervention program on fatigue severity and its impact in participants with primary biliary cholangitis (PBC). Fatigue will be assessed using the Primary Biliary Cholangitis-40 (PBC-40) fatigue domain, which consists of 11 items scored from 1 to 5. Scoring Range: 11 to 55; higher scores indicate greater fatigue.
Change in Fatigue Severity Assessed by Visual Analogue Scale — Baseline (week 0), post-intervention (week 8), and end of maintenance phase (6 months). To evaluate the effect of a non-pharmacological multimodal intervention program on fatigue severity and its impact in participants with primary biliary cholangitis (PBC). Fatigue will be assessed using the Visual Analogue Scale (VAS) for fatigue, which captures the participant's perception of fatigue severity. Scoring Range: 0 (no fatigue) to 10 (worst imaginable fatigue).
Change in Fatigue Impact Assessed by Fatigue Impact Scale (FIS) — Baseline (week 0), post-intervention (week 8), and end of maintenance phase (6 months). To evaluate the effect of a non-pharmacological multimodal intervention program on fatigue severity and its impact in participants with primary biliary cholangitis (PBC). Fatigue will be assessed using the Modified Fatigue Impact Scale (MFIS), which assesses the impact of fatigue on physical, cognitive, and psychosocial functioning. Scoring Range: 0 to 84; higher scores indicate greater fatigue-related impairment
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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