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PBC Induced Fatigue Treated With Thiamine

Phase 4
Conditions
Primary Biliary Cirrhosis
Interventions
Drug: Placebo
Registration Number
NCT04893993
Lead Sponsor
Henning Grønbæk
Brief Summary

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterised by destruction of the intrahepatic bile ducts leading to liver inflammation and fibrosis, and ultimately liver cirrhosis and end-stage liver disease. More than 50% of patients with PBC suffer from chronic fatigue, and approximately 20% suffer from severe fatigue with negative impact on their quality of life. Although fatigue is a large problem in patients with PBC, no effective treatments are available.

A Danish intervention study have shown that high dose oral thiamine (Vitamin B1) were effective in treating chronic fatigue in patients with inflammatory bowel disease. In this study, only few and minor adverse events to thiamine treatment were observed. Although the precise mechanism of work remains unknown, the investigators see no reason that this cannot be transferred topatients with PBC. Hence, the investigators aim to conduct a study investigating the use of oral thiamine in chronic fatigued patients with PBC.

The study will be conducted as a double-blinded, placebo-controlled, randomised, crossover trial including 36 patients with PBC and with a higher fatigue level than in the general population for more than six months. The patients will be randomised into one of two 3x4 weeks setups; 1) thiamine for four weeks followed by four weeks washout and finally four weeks of placebo or 2) placebo for four weeks followed by four weeks washout and finally four weeks of thiamine. The primary endpoint is to investigate the fatigue-level before and after treatment with thiamine and placebo using every patient as their own control. Fatigue-level will be measured using international validated questionnaires. The doses of thiamine are calculated based on the patient gender and weight. All patients will be included in the outpatient clinic at the Department of Hepatology and Gastroenterology at Aarhus University Hospital.

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
36
Inclusion Criteria
  • PBC for more than 3 months
  • PBC-40 fatigue score >32
  • Fatigued for at least 6 months
Exclusion Criteria
  • Comorbidity that can explain fatigue
  • Non-compliant patients
  • Pregnancy
  • Expected surgical interventions during the study period
  • Chronic kidney disease (eGFR<60)

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Thiamine-PlaceboPlacebo12 weeks: 4 weeks with Thiamine, 4 weeks wash-out, 4 weeks placebo Both placebo and Thiamine are oral tablets of 300mg pr. tablet. The dosage depends on gender and weight of the participants, with a maximum of 1800mg intake pr. day.
Placebo-ThiaminePlacebo12 weeks: 4 weeks placebo, 4 weeks wash-out, 4 weeks with Thiamine Both placebo and Thiamine are oral tablets of 300mg pr. tablet. The dosage depends on gender and weight of the participants, with a maximum of 1800mg intake pr. day.
Thiamine-PlaceboThiamine12 weeks: 4 weeks with Thiamine, 4 weeks wash-out, 4 weeks placebo Both placebo and Thiamine are oral tablets of 300mg pr. tablet. The dosage depends on gender and weight of the participants, with a maximum of 1800mg intake pr. day.
Placebo-ThiamineThiamine12 weeks: 4 weeks placebo, 4 weeks wash-out, 4 weeks with Thiamine Both placebo and Thiamine are oral tablets of 300mg pr. tablet. The dosage depends on gender and weight of the participants, with a maximum of 1800mg intake pr. day.
Primary Outcome Measures
NameTimeMethod
FatigueAfter 4 weeks active treatment

Change in levels of fatigue measured by the Primary biliary cholangitis-40 (PBC-40) fatigue domain. The fatigue domain measures the severity of fatigue on a scale from 11-55, where 55 is maximun fatigue. A change in PBC-40 fatigue domain of 5 points or more is regarded as a clinical relevant change.

Secondary Outcome Measures
NameTimeMethod
FatigueWeek 8 and 12

Change in levels of fatigue measured by the Primary biliary cholangitis-40 (PBC-40) fatigue domain. The fatigue domain measures the severity of fatigue on a scale from 11-55, where 55 is maximun fatigue. A change in PBC-40 fatigue domain of 5 points or more is regarded as a clinical relevant change.

Health-related Quality of LifeWeek 4, 8 and 12

Changes in Health-related Quality of Life, measured by the generic EQ-5D-5L tool (mainly the VAS-scale from 0-100, where 100 is best).

Disease-specific Quality of LifeWeek 4, 8 and 12

Changes in Health-related Quality of life, measured by the disease specific Primary biliary Cholangitis-40 (PBC-40).

Trial Locations

Locations (1)

Department of Hepatology and Gastroenterology, Aarhus University Hospital, Denmark

🇩🇰

Aarhus N, Region Midtjylland, Denmark

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