Clinical Trial Results:
Thiamin against robust IBD fatigue - The effect of oral thiamin supplement in 4 weeks to patients with inflammatory bowel disease (IBD) in remission and chronic fatigue. A randomised placebo controlled crossover study

Trial information Top of page
Trial identification
Sponsor protocol code	TARIF
Additional study identifiers
ISRCTN number	-
US NCT number	NCT03634735
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	Aarhus University Hospital
Sponsor organisation address	Palle Juul-Jensens Boulevard 99, Aarhus N, Denmark, 8230
Public contact	Palle Bager, Aarhus University Hospital, 45 51500697, pallbage@rm.dk
Scientific contact	Christian Lodberg Hvas, Aarhus University Hospital, 45 28351839, christian.hvas@auh.rm.dk
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)	No
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	01 Sep 2021
Is this the analysis of the primary completion data?	Yes
Primary completion date	27 Oct 2020
Global end of trial reached?	Yes
Global end of trial date	27 Oct 2020
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	To investigate if the levels of fatigue can be reduced after 4 weeks treatment with Thiamin, among patients with inflammatory bowel disease in remission and chronic fatigue
Protection of trial subjects	Safety were continuous monitored for all subjects
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	27 Nov 2018
Long term follow-up planned	Yes
Long term follow-up rationale	Safety, Efficacy, Scientific research
Long term follow-up duration	6 Months
Independent data monitoring committee (IDMC) involvement?	Yes
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	Denmark: 40
Worldwide total number of subjects	40
EEA total number of subjects	40
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age < 37 wk	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	0
Adults (18-64 years)	39
From 65 to 84 years	1
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	All subjects were included from the outpatient clinic at Aarhus University Hospital, Denmark.
Pre-assignment
Screening details	A total of 84 patients were screened. 44 were not included, primary due to: low level of fatigue, fatigue duration or disease activity.
Period 1
Period 1 title	Blinded period
Is this the baseline period?	Yes
Allocation method	Randomised - controlled
Blinding used	Double blind
Roles blinded	Subject, Investigator, Monitor
Arms
Are arms mutually exclusive	No
Arm title	Intervention
Arm description	Thiamine tablets for 4 weeks. Daily dose 600 -1800 mg, depending of body weight and gender.
Arm type	Experimental
Investigational medicinal product name	Thiamine
Investigational medicinal product code
Other name
Pharmaceutical forms	Tablet
Routes of administration	Oral use
Dosage and administration details	600 - 1800 mg daily
Arm title	Placebo
Arm description	Placebo tablets for 4 weeks. The number of tablet taken was depending of body weight and gender and was equal to the number of tablets taken in the intervention arm.
Arm type	Placebo
Investigational medicinal product name	Placebo
Investigational medicinal product code
Other name
Pharmaceutical forms	Tablet
Routes of administration	Oral use
Dosage and administration details	2 - 6 tablets daily for 4 weeks
Number of subjects in period 1 Intervention Placebo Started 40 40 Completion of the blinded part 40 40 Completed 40 40
Period 2
Period 2 title	Unblinded period
Is this the baseline period?	No
Allocation method	Randomised - controlled
Blinding used	Not blinded
Arms
Are arms mutually exclusive	Yes
Arm title	Intervention
Arm description	300 mg thiamine tablets daily for 12 weeks
Arm type	Experimental
Investigational medicinal product name	Thiamine
Investigational medicinal product code
Other name
Pharmaceutical forms	Tablet
Routes of administration	Oral use
Dosage and administration details	300 mg daily for 12 weeks
Arm title	No thiamine
Arm description	No thiamine supplementation for 12 weeks
Arm type	No intervention
Investigational medicinal product name	No investigational medicinal product assigned in this arm
Number of subjects in period 2 Intervention No thiamine Started 20 20 End of open label 20 20 Completed 20 20
Period 3
Period 3 title	Follow up period
Is this the baseline period?	No
Allocation method	Non-randomised - controlled
Blinding used	Not blinded
Arms
Arm title	Observation
Arm description	All subjects were followed for 6 months after the two interventions studies
Arm type	No intervention
Investigational medicinal product name	No investigational medicinal product assigned in this arm
Number of subjects in period 3 Observation Started 40 End of follow up 38 Completed 38 Not completed 2      Lost to follow-up 2

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	Blinded period
Reporting group description	40 subjects were enrolled in the intervention trail. 20 subjects were enrolled for one visit only and acted as a control group for the group of 40 subjects
Reporting group values Blinded period Total Number of subjects 40 40 Age categorical Units: Subjects     In utero 0 0     Preterm newborn infants (gestational age < 37 wks) 0 0     Newborns (0-27 days) 0 0     Infants and toddlers (28 days-23 months) 0 0     Children (2-11 years) 0 0     Adolescents (12-17 years) 0 0     Adults (18-64 years) 39 39     From 65-84 years 1 1     85 years and over 0 0 Gender categorical Units: Subjects     Female 35 35     Male 5 5

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	Intervention
Reporting group description	Thiamine tablets for 4 weeks. Daily dose 600 -1800 mg, depending of body weight and gender.
Reporting group title	Placebo
Reporting group description	Placebo tablets for 4 weeks. The number of tablet taken was depending of body weight and gender and was equal to the number of tablets taken in the intervention arm.
Reporting group title	Intervention
Reporting group description	300 mg thiamine tablets daily for 12 weeks
Reporting group title	No thiamine
Reporting group description	No thiamine supplementation for 12 weeks
Reporting group title	Observation
Reporting group description	All subjects were followed for 6 months after the two interventions studies

End points Top of page

Primary: Fatigue improvement Top of page
End point title	Fatigue improvement
End point description	An improvement ≥ 3 points on the IBD-F, Section I scale was defined as a clinically relevant improvement
End point type	Primary
End point timeframe	After 4 weeks of treatment compared to placebo
End point values Intervention Placebo Number of subjects analysed 40 40 Units: Fatigue severity on a scale     IBD-F, Section I 40 40
Statistical analysis title	Comparison between groups
Statistical analysis description	Change in fatigue severity: intervention period compared to placebo period
Comparison groups	Placebo v Intervention
Number of subjects included in analysis	80
Analysis specification	Pre-specified
Analysis type	non-inferiority
P-value	< 0.001 [1]
Method	t-test, 2-sided
Parameter type	Mean difference (final values)
Point estimate	4.5
Confidence interval
level	95%
sides	2-sided
lower limit	2.6
upper limit	6.2
Notes [1] - A reduction of fatigue in the intervention period of 4.5 points compared to an increase in fatigue of 0.75 points in the placebo period.

Primary: Fatigue improvement Top of page

Primary: Fatigue maintenance Top of page
End point title	Fatigue maintenance
End point description	The 20 subjects who were randomised to thiamine 300 mg daily were compared to the 20 subjects who did not receive thiamine
End point type	Primary
End point timeframe	After 12 weeks of thiamine treatment vs. no thiamine
End point values Intervention No thiamine Number of subjects analysed 20 20 Units: Fatigue severity     IBD.F, Section I 20 20
Statistical analysis title	Comparison between groups
Comparison groups	Intervention v No thiamine
Number of subjects included in analysis	40
Analysis specification	Pre-specified
Analysis type	non-inferiority [2]
P-value	= 0.75 [3]
Method	t-test, 2-sided
Parameter type	Mean difference (final values)
Point estimate	1.4
Confidence interval
level	95%
sides	2-sided
lower limit	-0.6
upper limit	3.5
Variability estimate	Standard deviation
Dispersion value	3.5
Notes [2] - Comparison of the fatigue severity between groups after 12 weeks [3] - The thiamine group had a mean increase of fatigue of 1.4 points vs. the no thiamine group who had an increase of 1.9. point.

Primary: Fatigue maintenance Top of page

Adverse events Top of page
Adverse events information [1]
Timeframe for reporting adverse events	From study start to end of trial
Adverse event reporting additional description	Data on adverse events were collected at every visit. Furthermore, the subjects were able to report adverse events at any time during the study period
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	2.1
Frequency threshold for reporting non-serious adverse events: 5%
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: We found no serious adverse events. The number of adverse events were < 5 %

Adverse events Top of page

More information Top of page
Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? No
Interruptions (globally)
Were there any global interruptions to the trial? No
Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
None reported
Online references
http://www.ncbi.nlm.nih.gov/pubmed/33210299

More information Top of page