PBC Induced Fatigue Treated With Thiamine

NCT04893993 | Unknown Phase 4 DMC

• 1 other identifier: PIFT AU
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Primary Biliary Cirrhosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Disease-specific Quality of Life

  Week 4, 8 and 12

• Health-related Quality of Life

  Week 4, 8 and 12

• Fatigue

  Week 8 and 12

Study Arms (2)

Thiamine-Placebo

OTHER

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; Drug: Placebo

Placebo-Thiamine

OTHER

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; Drug: Placebo

Interventions

Thiamine DRUG

Tablets. 300mg/tablet. Dosage depends on gender and weight

Placebo-Thiamine; Thiamine-Placebo

Placebo DRUG

Tablets. Same number of tablets as Thiamine

Placebo-Thiamine; Thiamine-Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• PBC for more than 3 months
• PBC-40 fatigue score \>32
• Fatigued for at least 6 months

You may not qualify if:

• Comorbidity that can explain fatigue
• Non-compliant patients
• Pregnancy
• Expected surgical interventions during the study period
• Chronic kidney disease (eGFR\<60)

Sponsors & Collaborators

• Henning Grønbæk: lead
• Aarhus University Hospital: collaborator
• Hospitalsapoteket Region Midtjylland: collaborator
• GCP-unit at Aarhus University Hospital, Aarhus, Denmark: collaborator
• Region Hovedstadens Apotek: collaborator

Study Sites (1)

Department of Hepatology and Gastroenterology, Aarhus University Hospital, Denmark

Aarhus N, Central Jutland, 8200, Denmark

RECRUITING

Related Publications (1)

• Bager P, Bossen L, Gantzel R, Gronbaek H. High-dose oral thiamine versus placebo for chronic fatigue in patients with primary biliary cholangitis: A crossover randomized clinical trial. PLoS One. 2024 Mar 29;19(3):e0301354. doi: 10.1371/journal.pone.0301354. eCollection 2024.

  PMID: 38551983 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Interventions

Thiamine

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

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Central Study Contacts

Henning Grønbæk, Professor

CONTACT

+45 21679281; henngroe@rm.dk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD., Clinical professor, consultant

Study Record Dates

• First Submitted: May 4, 2021
• First Posted: May 20, 2021
• Study Start: May 12, 2021
• Primary Completion: December 31, 2022
• Study Completion: December 1, 2023
• Last Updated: May 20, 2021

Record last verified: 2021-05

Locations

DK (1)