PBC Induced Fatigue Treated With Thiamine (PIFT)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Primary Biliary Cirrhosis
• Intervention / Treatment: Drug: Thiamine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Henning Grønbæk, Professor; Phone Number: +45 21679281; Email: henngroe@rm.dk

Study Locations

• Denmark
  • Region Midtjylland
    • Aarhus N, Region Midtjylland, Denmark, 8200
      • Recruiting
      • Department of Hepatology and Gastroenterology, Aarhus University Hospital, Denmark
      • Contact: Henning Grønbæk, Professor; Phone Number: +45 21679281; Email: henngroe@rm.dk
      • Contact: Lars Bossen, MD; Phone Number: +45 22800676; Email: larsbossen@clin.au.dk
      • Sub-Investigator: Palle Bager, PhD
      • Sub-Investigator: Rasmus Gantzel, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Henning Grønbæk
• Collaborators: Aarhus University Hospital; Region Hovedstadens Apotek; Hospitalsapoteket Region Midtjylland; GCP-unit at Aarhus University Hospital, Aarhus, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2021
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: May 4, 2021
• First Submitted That Met QC Criteria: May 19, 2021
• First Posted (Actual): May 20, 2021

Study Record Updates

• Last Update Posted (Actual): May 20, 2021
• Last Update Submitted That Met QC Criteria: May 19, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Liver Cirrhosis; Fatigue; Liver Cirrhosis, Biliary; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Thiamine
• Other Study ID Numbers: PIFT AU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No