PBC Induced Fatigue Treated With Thiamine

Study Overview
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Brief Summary
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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.

Official Title
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PBC Induced Fatigue Treated With Thiamine (PIFT) - The Effect of Oral Thiamine Supplement in 4 Weeks to Patients With Primary Biliary Cholangitis (PBC) and Chronic Fatigue. A Randomised Placebo Controlled Crossover Study

Conditions
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Primary Biliary Cirrhosis

Intervention / Treatment
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* Drug: Thiamine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Thiamine-Placebo<br>12 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. | Drug: Thiamine<br>* Tablets. 300mg/tablet. Dosage depends on gender and weight<br>Drug: Placebo<br>* Tablets. Same number of tablets as Thiamine<br>|
| Other: Placebo-Thiamine<br>12 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. | Drug: Thiamine<br>* Tablets. 300mg/tablet. Dosage depends on gender and weight<br>Drug: Placebo<br>* Tablets. Same number of tablets as Thiamine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fatigue | 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. | After 4 weeks active treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-specific Quality of Life | Changes in Health-related Quality of life, measured by the disease specific Primary biliary Cholangitis-40 (PBC-40). | Week 4, 8 and 12 | 
| Health-related Quality of Life | 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). | Week 4, 8 and 12 | 
| Fatigue | 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. | Week 8 and 12 |