RELIEF: Multimodal Prehabilitation to Treat Fatigue in Patients With Primary Biliary Cholangitis

NCT07161245 | Recruiting

• 1 other identifier: RELIEF/2025
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Primary Biliary Cholangitis (PBC)

Keywords

FATIGUE; PREHABILITATION; PHYSICAL ACTIVITY; MINDFULNESS MEDITATION; NUTRITION; QUALITY OF LIFE

Outcome Measures

Primary Outcomes (3)

• Change in Fatigue Severity Assessed by PBC-40

  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.

  Baseline (week 0), post-intervention (week 8), and end of maintenance phase (6 months).

• Change in Fatigue Severity Assessed by Visual Analogue Scale

  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).

  Baseline (week 0), post-intervention (week 8), and end of maintenance phase (6 months).

• Change in Fatigue Impact Assessed by Fatigue Impact Scale (FIS)

  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

  Baseline (week 0), post-intervention (week 8), and end of maintenance phase (6 months).

Secondary Outcomes (15)

• Change in Cognitive Symptoms Assessed by PBC-40

  Baseline, week 8 and/or after the exercise phase, and end of trial.

• Change in Extrahepatic Symptoms Assessed by PBC-40

  Baseline, week 8 and/or after the exercise phase, and end of trial.

• Change in Quality of Life Assessed by EQ-5D-5L Index Score

  Baseline, week 8 and/or after the exercise phase, and end of trial.

• Change in Self-Perceived Health Status Assessed by EQ Visual Analogue Scale

  Baseline, week 8 and/or after the exercise phase, and end of trial.

• Change in Disability Assessed by the WHO Disability Assessment Schedule (WHODAS 2.0)

  Baseline, week 8 and/or after the exercise phase, and end of trial.

Study Arms (2)

Multimodal prehabilitation

EXPERIMENTAL

8 weeks program of tailored physical exercise program with nutritional and psychological counselling to be carried out to a patient on the basis of his/her health condition, social circumstances and adherence profile.

Other: Multimodal prehabilitation

Standard of care

OTHER

Standard Counselling: Patients in the control group will follow standard of care of the hospital and will be given general recommendations on physical activity, nutrition and stress/anxiety management.

Other: standard of care

Interventions

Multimodal prehabilitation OTHER

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.

Multimodal prehabilitation

standard of care OTHER

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.

Standard of care

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• PBC diagnosis according to EASL guidelines
• Moderate - severe fatigue defined by ≥ 29 points in PBC-40 questionnaire

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospital Clinic of Barcelona: lead

Study Sites (1)

Hospital Clinic de Barcelona

Barcelona, Barcelona, 08036, Spain

RECRUITING

Related Publications (32)

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MeSH Terms

Conditions

Liver Cirrhosis, Biliary; Fatigue; Motor Activity

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Sergio Rodríguez Tajes, MD, PhD

  Hospital Clinic of Barcelona

  PRINCIPAL INVESTIGATOR

• Marta Ubré Lorenzo, MD, PhD

  Hospital Clinic of Barcelona

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Helena Hernández Évole, MD

CONTACT

+34 932 27 54 00; HEHERNANDEZ@clinic.cat

Sergio Rodríguez Tajes, MD, PhD

CONTACT

SRODRIGUEZ@CLINIC.CAT

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants with primary biliary cholangitis (PBC) under follow-up in hepatology outpatient clinics who present with moderate to severe fatigue, as defined by a score greater than 29 on the PBC-40 questionnaire, and who agree to participate in the study after providing informed consent, will be eligible for inclusion. Once enrolled, participants with PBC and fatigue will be randomly assigned to either receive the multimodal intervention for 8 weeks or be allocated to the control group. Randomization will be performed using simple randomization via the REDCap platform. For the control group, after the initial 8-week period, the opportunity to participate in the multimodal rehabilitation program will be offered. Subsequently, both groups, after completing the 8-week intervention, will continue with the remote phase of the program for an additional six months of follow-up.

Study Record Dates

• First Submitted: June 2, 2025
• First Posted: September 8, 2025
• Study Start: February 6, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: September 8, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)