The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12614000755639
Ethics application status
Approved
Date submitted
4/07/2014
Date registered
16/07/2014
Date last updated
8/01/2019
Date data sharing statement initially provided
8/01/2019
Date results information initially provided
8/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Thiamine to improve stem cell function in patients undergoing bypass surgery: a randomised controlled trial
Scientific title
A randomised trial comparing high-dose thiamine to placebo in patients undergoing coronary artery bypass surgery with proliferation of resident cardiac progenitor cells as measured by bromodeoxyuridine (BrdU) assay as primary outcome
Secondary ID [1] 284889 0
Nil
Universal Trial Number (UTN)
U1111-1158-2217
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heart failure 292334 0
Coronary artery disease 292335 0
Diabetes mellitus 292336 0
Condition category
Condition code
Cardiovascular 292668 292668 0 0
Coronary heart disease
Metabolic and Endocrine 292763 292763 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Thiamine two 500mg capsules twice daily for 3-5 days prior to surgery. Treatment starts after the surgical list for the following week has been finalised and continues until the day before surgery. Adherence and adverse effects of treatment will be monitored by a pill count, questionnaire and blood tests prior to surgery.
Intervention code [1] 289701 0
Treatment: Drugs
Comparator / control treatment
Placebo (maltodextrin) two 500mg capsules twice daily for 3-5 days prior to surgery.
Control group
Placebo

Outcomes
Primary outcome [1] 292512 0
Resident cardiac progenitor cell proliferation as measured by BrdU assay
Timepoint [1] 292512 0
At time of coronary artery bypass grafting
Secondary outcome [1] 309128 0
Ability of resident cardiac progenitor cells to differentiate into cardiomyocytes, as measured by the number of GATA-4 and connexin-43 positive cells after exposure to differentiation medium
Timepoint [1] 309128 0
At time of coronary artery bypass surgery
Secondary outcome [2] 309129 0
Level of activation of pentose phosphate pathway as measured by the level of transketolase in resident cardiac progenitor cells
Timepoint [2] 309129 0
At the time of coronary artery bypass surgery
Secondary outcome [3] 309385 0
Circulating thiamine levels
Timepoint [3] 309385 0
At the time of coronary artery bypass surgery.
Secondary outcome [4] 309386 0
Adverse effects assessment: headache, nausea, irritability, insomnia, rapid pulse, muscle weakness. These are assessed by interview and examination of vital signs.
Timepoint [4] 309386 0
Day 3 (and day 4 if applicable) of being on study medication.

Eligibility
Key inclusion criteria
1. Patients listed for inpatient coronary artery bypass surgery due to atherosclerotic coronary artery disease and
2. Aged 50 years and over and
3. Left ventricular systolic function normal on echocardiography (ejection fraction more than or equal to 50%) performed during this inpatient stay (or within three months if no myocardial infarction has occurred between date of echocardiogram and date of enrollment).
Minimum age
50 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Left ventricular systolic function impaired (echocardiographic ejection fraction < 50%) or
2. Renal failure with creatinine > 200 umol/l or requiring renal replacement therapy or
3. Already taking thiamine supplementation or
4. Previously had an adverse reaction to thiamine, or a supplement or medication containing thiamine or
5. Previous or current history of alcohol related problems. This refers to a previous diagnosis of a medical condition thought to be caused or exacerbated by alcohol, or harmful use of alcohol (International Classification of Diseases version 10 codes F10.0 to F10.9) or
6. Other major medical conditions that, in the opinion of the investigator, would make randomisation of the participant to thiamine unsafe or undesirable.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Numbered containers determined by computer-based randomisation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomisation according to randomization.com
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
A standard two-tailed t-test will be used to compare the primary outcome between treated and non-treated groups, using an intention-to-treat analysis. Separate analysis of the primary outcomes stratified by diabetic status will be performed using a t-test.
For secondary analyses, differences across multiple groups will be assessed using an analysis of variance (ANOVA) test followed by a Sidak-Holm multiple comparison test. Comparison between two groups will be assessed using t-tests.

Pre-specified subgroup analysis is according to diabetic status.

The sample size has been calculated to provide more than 90% power in the subgroups to detect a two-tailed 30% difference in primary outcome with treatment at a significance level of 0.05.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 6182 0
New Zealand
State/province [1] 6182 0
Otago

Funding & Sponsors
Funding source category [1] 289514 0
Government body
Name [1] 289514 0
Lottery Health Research
Address [1] 289514 0
Local Government and Community Branch
Department of Internal Affairs
PO Box 805
Wellington 6140
Country [1] 289514 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
Department of Medicine
Dunedin School of Medicine
PO Box 56
Dunedin 9054
New Zealand
Country
New Zealand
Secondary sponsor category [1] 288201 0
None
Name [1] 288201 0
Address [1] 288201 0
Country [1] 288201 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291259 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 291259 0
c/o Ministry of Health
No 1 The Terrace
PO Box 5013
Wellington 6145
Ethics committee country [1] 291259 0
New Zealand
Date submitted for ethics approval [1] 291259 0
30/06/2014
Approval date [1] 291259 0
20/10/2014
Ethics approval number [1] 291259 0

Summary
Brief summary
Cardiac dysfunction is common in patients undergoing coronary artery bypass grafting (CABG) surgery. The heart’s intrinsic regenerative capability is related to the presence and function of resident cardiac stem cells, but there are limited ways of improving this capability. We have shown that thiamine analogues increase the profileration of resident cardiac stem cells in-vitro, by stimulating the pentose phosphate pathway. In addtion, we have shown that patients with type 2 diabetes have reduced number and less proliferation of resident cardiac stem cells, due to dysfunction of the pentose phosphate pathway. We aim to translate these findings to humans, by randomising patients undergoing CABG surgery to either short-term high dose thiamine or placebo, with a primary endpoint of the ability of resident cardiac stem cells to proliferate. In addition to the valuable findings of the trial itself, if we show that this approach is successful, this study could directly be used to design a larger clinical outcome driven randomised control trial.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 49558 0
Prof Michael Williams
Address 49558 0
Department of Cardiology,
7th Floor, Dunedin Hospital
201 Great King Street
Dunedin 9016
Country 49558 0
New Zealand
Phone 49558 0
+64 3 474 0999
Fax 49558 0
Email 49558 0
michael.williams@otago.ac.nz
Contact person for public queries
Name 49559 0
Ms Mary Blok
Address 49559 0
Research Nurse
Department of Cardiology
9th Floor, Dunedin Hospital
201 Great King Street
Dunedin 9016
Country 49559 0
New Zealand
Phone 49559 0
+64 3 474 0999
Fax 49559 0
Email 49559 0
cardiology.research@otago.ac.nz
Contact person for scientific queries
Name 49560 0
Dr Sean Coffey
Address 49560 0
Department of Medicine,
Dunedin School of Medicine,
PO Box 56
Dunedin 9054
Country 49560 0
New Zealand
Phone 49560 0
+64 34740999
Fax 49560 0
Email 49560 0
sean.coffey@otago.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Ethics Committee approval was only granted for data use by the local study investigators.
What supporting documents are/will be available?
Study protocol
How or where can supporting documents be obtained?
Type [1] 945 0
Study protocol
Citation [1] 945 0
Link [1] 945 0
Email [1] 945 0
Other [1] 945 0
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary