Primary Biliary CirrhosisPhase 4PIFTNCT04893993
PBC Induced Fatigue Treated With Thiamine
A Phase 4 study testing Thiamine in people with Primary Biliary Cirrhosis, run by Henning Grønbæk at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Biliary Cirrhosis
- What is being tested?
- Thiamine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteDenmark
- Study dates
- 12 May 2021to Dec 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- PBC for more than 3 months
- PBC-40 fatigue score >32
- Fatigued for at least 6 months
Who cannot join
- Comorbidity that can explain fatigue
- Non-compliant patients
- Pregnancy
- Expected surgical interventions during the study period
- Chronic kidney disease (eGFR<60)
Trial locations and contacts
1 site in 1 country.
Denmark1 site, 1 recruiting
- Recruiting
Department of Hepatology and Gastroenterology, Aarhus University Hospital, Denmark
Aarhus N, Central Jutland, 8200
Henning Grønbæk, Professor, +45 21679281, henngroe@rm.dk
Lars Bossen, MD, +45 22800676, larsbossen@clin.au.dk
About this study
Official title: 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.
- Conditions
- Primary Biliary Cirrhosis
- Being tested
- Thiamine, Placebo
- Medical subject headings
- Liver Cirrhosis, Biliary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ThiamineDrug
Tablets. 300mg/tablet. Dosage depends on gender and weight
PlaceboDrug
Tablets. Same number of tablets as Thiamine
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Thiamine; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: After 4 weeks active treatment
Secondary outcomes (3)
Disease-specific Quality of Life
Changes in Health-related Quality of life, measured by the disease specific Primary biliary Cholangitis-40 (PBC-40).
Measured: 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).
Measured: 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.
Measured: Week 8 and 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2021
- Study start12 May 2021
- Primary completion31 Dec 2022 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Primary Biliary CirrhosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Henning Grønbæk
- Sponsor type
- University, hospital or other
- Collaborators
- Aarhus University Hospital, Hospitalsapoteket Region Midtjylland, GCP-unit at Aarhus University Hospital, Aarhus, Denmark, Region Hovedstadens Apotek
- Responsible party
- Sponsor-investigator, Henning Grønbæk, Aarhus University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04893993
- Sponsor's protocol ID
- PIFT AU
- Acronym
- PIFT
- Status last verified
- May 2021
- First submitted
- 4 May 2021
- Last updated
- 20 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 38551983
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04893993
- Acronym / sponsor ID
- PIFT / PIFT AU
- Conditions
- Primary Biliary Cirrhosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Henning GrønbækUniversity, hospital or other
- Collaborators
- Aarhus University Hospital, Hospitalsapoteket Region Midtjylland, GCP-unit at Aarhus University Hospital, Aarhus, Denmark, Region Hovedstadens Apotek
- Study start
- 12 May 2021 (actual)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 20 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Thiamine-Placebo | Other | Drug: Thiamine, Drug: Placebo12 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-Thiamine | Other | Drug: Thiamine, Drug: Placebo12 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- PBC for more than 3 months
- PBC-40 fatigue score >32
- Fatigued for at least 6 months
Key exclusion criteria (5 listed)
- Comorbidity that can explain fatigue
- Non-compliant patients
- Pregnancy
- Expected surgical interventions during the study period
- Chronic kidney disease (eGFR<60)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ThiamineTablets. 300mg/tablet. Dosage depends on gender and weight | Drug | Placebo-Thiamine, Thiamine-Placebo |
| PlaceboTablets. Same number of tablets as Thiamine | Drug | Placebo-Thiamine, Thiamine-Placebo |
Primary outcome
Fatigue
Time frame: After 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.
3 secondary outcomes
Disease-specific Quality of Life
Time frame: Week 4, 8 and 12
Health-related Quality of Life
Time frame: Week 4, 8 and 12
Fatigue
Time frame: Week 8 and 12
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2021.
- Derived from this study: PubMed 38551983Bager 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Thiamine in people with Primary Biliary Cirrhosis, run by Henning Grønbæk at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Henning Grønbæk, Professor (+45 21679281, henngroe@rm.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fatigue (time frame: After 4 weeks active treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04893993, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2021.