ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12614000755639

Ethics application status

Approved

Date submitted

4/07/2014

Date registered

16/07/2014

Date last updated

11/11/2021

Date data sharing statement initially provided

8/01/2019

Date results 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]

Nil

Universal Trial Number (UTN)

U1111-1158-2217

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Heart failure

Coronary artery disease

Diabetes mellitus

Condition category

Condition code

Cardiovascular

Coronary heart disease

Metabolic and Endocrine

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]

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]

Resident cardiac progenitor cell proliferation as measured by BrdU assay

Timepoint [1]

At time of coronary artery bypass grafting

Secondary outcome [1]

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]

At time of coronary artery bypass surgery

Secondary outcome [2]

Level of activation of pentose phosphate pathway as measured by the level of transketolase in resident cardiac progenitor cells

Timepoint [2]

At the time of coronary artery bypass surgery

Secondary outcome [3]

Circulating thiamine levels

Timepoint [3]

At the time of coronary artery bypass surgery.

Secondary outcome [4]

Adverse effects assessment: headache, nausea, irritability, insomnia, rapid pulse, muscle weakness. These are assessed by interview and examination of vital signs.

Timepoint [4]

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

Sex

Both males and females

Can healthy volunteers participate?

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

1/03/2015

Actual

10/04/2015

Date of last participant enrolment

Anticipated

Actual

22/03/2017

Date of last data collection

Anticipated

Actual

17/09/2018

Sample size

Target

Accrual to date

Final

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Otago

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

Lottery Health Research

Address [1]

Local Government and Community Branch
Department of Internal Affairs
PO Box 805
Wellington 6140

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Southern Health and Disability Ethics Committee

Ethics committee address [1]

c/o Ministry of Health
No 1 The Terrace
PO Box 5013
Wellington 6145

Ethics committee country [1]

New Zealand

Date submitted for ethics approval [1]

30/06/2014

Approval date [1]

20/10/2014

Ethics approval number [1]

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

Prof Michael Williams

Address

Department of Cardiology,
7th Floor, Dunedin Hospital
201 Great King Street
Dunedin 9016

Country

New Zealand

Phone

+64 3 474 0999

Fax

michael.williams@otago.ac.nz

Contact person for public queries

Name

Mary Blok

Address

Research Nurse
Department of Cardiology
9th Floor, Dunedin Hospital
201 Great King Street
Dunedin 9016

Country

New Zealand

Phone

+64 3 474 0999

Fax

cardiology.research@otago.ac.nz

Contact person for scientific queries

Name

Sean Coffey

Address

Department of Medicine,
Dunedin School of Medicine,
PO Box 56
Dunedin 9054

Country

New Zealand

Phone

+64 34740999

Fax

sean.coffey@otago.ac.nz

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
945	Study protocol					366625-(Uploaded-07-01-2019-13-18-57)-Study-related document.pdf

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Thiamine increases resident endoglin positive cardiac progenitor cells and atrial contractile force in humans: A randomised controlled trial.	2021	https://dx.doi.org/10.1016/j.ijcard.2021.08.039

N.B. These documents automatically identified may not have been verified by the study sponsor.

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Documents added manually

Documents added automatically