Clinical Trial Results:
PBC induced fatigue treated with thiamine
- The effect of oral thiamine supplement in 4 weeks to patients with primary biliary cholangitis (PBC) and chronic fatigue.
A randomised, double-blinded, placebo-controlled, crossover study
Summary
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EudraCT number |
2020-004935-26 |
Trial protocol |
DK |
Global end of trial date |
30 Aug 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Oct 2023
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First version publication date |
08 Oct 2023
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
PIFT
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04893993 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Aarhus University Hospital
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Sponsor organisation address |
Palle Juul-Jensens Boulevard 99, Aarhus N, Denmark, 8200
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Public contact |
Henning Grønbæk, Aarhus University Hospital, +45 21679281, henngroe@rm.dk
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Scientific contact |
Henning Grønbæk, Aarhus University Hospital, +45 21679281, henngroe@rm.dk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
01 Aug 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
30 Aug 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Aug 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To investigate if the levels of fatigue can be reduced after 4 weeks treatment with Thiamine, among patients with primary biliary cholangitis and chronic fatigue
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Protection of trial subjects |
The trial was conducted in accordance with the Declaration of Helsinki and the GCP principles and was monitored by the GCP unit at Aarhus and Aalborg University Hospitals
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Background therapy |
All patients received standard therapy for PBC i.e. UDCA and in some cases also bezafibrate. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
03 May 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Denmark: 36
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Worldwide total number of subjects |
36
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EEA total number of subjects |
36
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
28
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From 65 to 84 years |
8
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients with PBC were recruited at the outpatient clinic at the department of hepatology and gastroenterology, Aarhus University Hospital, Denmark Patients with PBC for more than 3 months, age ≥ 18 years, a total fatigue score on the PBC-40 questionnaire > 32 and a fatigue duration > 6 months were eligible for study inclusion | ||||||||||||||||||
Pre-assignment
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Screening details |
PBC patients complaining about fatigue were screened with the PBC-40 questionnaire, and if they scored above 32 on the fatigue subscale, they were informed about the study, signed informed consent and where screened with biochemistry before final inclusion. | ||||||||||||||||||
Period 1
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Period 1 title |
Treatment period 1
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst | ||||||||||||||||||
Blinding implementation details |
At the baseline visit, all participants received tablets for the two treatment periods in two separate anonymised containers, labelled E1 and E2, each containing 200 tables. The pharmacy made sealed envelopes with codes for the blinding. These envelopes remained sealed until the trial was completed.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Group 1 | ||||||||||||||||||
Arm description |
Thiamine | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Thiamine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
The daily dose depended on gender (female/male) and body weight (BW) according to the scheme: BW < 60 kg: 600/900 mg (2/3 tablets), BW 60-70 kg: 900/1200 mg (3/4 tablets), BW 71-80 kg: 1200/1500 mg (4/5 tablets), and BW > 80 kg: 1500/1800 mg (5/6 tablets)
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Arm title
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Group 2 | ||||||||||||||||||
Arm description |
Placebo | ||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
The daily dose depended on gender (female/male) and body weight (BW) according to the scheme: BW < 60 kg: 600/900 mg (2/3 tablets), BW 60-70 kg: 900/1200 mg (3/4 tablets), BW 71-80 kg: 1200/1500 mg (4/5 tablets), and BW > 80 kg: 1500/1800 mg (5/6 tablets)
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Period 2
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Period 2 title |
Wash out
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Is this the baseline period? |
No | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst | ||||||||||||||||||
Blinding implementation details |
At the baseline visit, all participants received tablets for the two treatment periods in two separate anonymised containers, labelled E1 and E2, each containing 200 tables.
Period 2 occured 4 weeks after the ending of period 1 (=4-week wash out)
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Group 1 | ||||||||||||||||||
Arm description |
Wash out | ||||||||||||||||||
Arm type |
No intervention | ||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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Group 2 | ||||||||||||||||||
Arm description |
Wash out | ||||||||||||||||||
Arm type |
No intervention | ||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Period 3
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Period 3 title |
Treatment period 2
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Is this the baseline period? |
No | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst | ||||||||||||||||||
Blinding implementation details |
At the baseline visit, all participants received tablets for the two treatment periods in two separate anonymised containers, labelled E1 and E2, each containing 200 tables.
Period 2 occured 4 weeks after the ending of period 1 (=4-week wash out)
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Group 1 | ||||||||||||||||||
Arm description |
Placebo | ||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
The daily dose depended on gender (female/male) and body weight (BW) according to the scheme: BW < 60 kg: 600/900 mg (2/3 tablets), BW 60-70 kg: 900/1200 mg (3/4 tablets), BW 71-80 kg: 1200/1500 mg (4/5 tablets), and BW > 80 kg: 1500/1800 mg (5/6 tablets)
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Arm title
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Group 2 | ||||||||||||||||||
Arm description |
Thiamine | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Thiamine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
The daily dose depended on gender (female/male) and body weight (BW) according to the scheme: BW < 60 kg: 600/900 mg (2/3 tablets), BW 60-70 kg: 900/1200 mg (3/4 tablets), BW 71-80 kg: 1200/1500 mg (4/5 tablets), and BW > 80 kg: 1500/1800 mg (5/6 tablets)
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Baseline characteristics reporting groups
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Reporting group title |
Group 1
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Reporting group description |
Thiamine | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Group 2
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Reporting group description |
Placebo | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Group 1
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Reporting group description |
Thiamine | ||
Reporting group title |
Group 2
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Reporting group description |
Placebo | ||
Reporting group title |
Group 1
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Reporting group description |
Wash out | ||
Reporting group title |
Group 2
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Reporting group description |
Wash out | ||
Reporting group title |
Group 1
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Reporting group description |
Placebo | ||
Reporting group title |
Group 2
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Reporting group description |
Thiamine |
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End point title |
Fatigue reduction | ||||||||||||||||||||
End point description |
Crossover analysis for fatigue scores and HRQoL scores averaged the between-treatment difference for each patient within each treatment period and then across both treatment periods, providing an estimate of treatment effect . In our primary analytical approach per the crossover analysis, group 1 was considered to be in the thiamine treatment group at week 4 and in the control group at week 12, whereas group 2 was considered to be in the control group at week 4 and in the thiamine treatment group at week 12. Differences in fatigue between week 4 and week 12 were compared between groups, using an unpaired t-test
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End point type |
Primary
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End point timeframe |
Week 4 to week 12
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Statistical analysis title |
Delayed treatment model | ||||||||||||||||||||
Statistical analysis description |
In our primary analytical approach per the crossover analysis, group 1 was considered to be in the thiamine treatment group at week 4 and in the control group at week 12, whereas group 2 was considered to be in the control group at week 4 and in the thiamine treatment group at week 12. Differences in fatigue between week 4 and week 12 were compared between groups, using an unpaired t-test.
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Comparison groups |
Group 1 v Group 2 v Group 1 v Group 2
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Number of subjects included in analysis |
68
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||
P-value |
< 0.05 | ||||||||||||||||||||
Method |
t-test, 2-sided | ||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||
Confidence interval |
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End point title |
HrQOL | ||||||||||||||||||||
End point description |
Crossover analysis for fatigue scores and HRQoL scores averaged the between-treatment difference for each patient within each treatment period and then across both treatment periods, providing an estimate of treatment effect. In our primary analytical approach per the crossover analysis, group 1 was considered to be in the thiamine treatment group at week 4 and in the control group at week 12, whereas group 2 was considered to be in the control group at week 4 and in the thiamine treatment group at week 12. Differences in fatigue between week 4 and week 12 were compared between groups, using an unpaired t-test.
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End point type |
Secondary
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End point timeframe |
Week 4 to Week 12
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No statistical analyses for this end point |
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Adverse events information [1]
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Timeframe for reporting adverse events |
Within the 12 week study period
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Adverse event reporting additional description |
Patients were told to report SAE/AE to the study personel. Patients where asked about SAE/AE at the end of the study. If patients reported SAE/AE's during the study period they were followed and monitored until the event resolved
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
None | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
0
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Reporting groups
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Reporting group title |
Group 1
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Reporting group description |
Thiamine first | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Group 2
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Reporting group description |
Placebo first | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: No non-serious adverse events were recorded for more than 5% of the cohort. |
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |