Thiamine to improve stem cell function in patients undergoing bypass surgery: a randomised controlled trial

Phase 2

Completed

• Conditions: Heart failure; Coronary artery disease; Diabetes mellitus; Cardiovascular - Coronary heart disease; Metabolic and Endocrine - Diabetes

• Registration Number: ACTRN12614000755639
• Lead Sponsor: niversity of Otago

Brief Summary

The heart’s intrinsic capability to repair itself is related to the presence and function of resident cardiac progenitor cells (CPCs). CPCs are cells that reside in the heart and can orchestrate this repair process. There are limited ways of improving this capability. In earlier lab based studies, we have shown that a thiamine like medicine increases the ability of these CPCs to proliferate. People having coronary artery bypass grafting (CABG) have narrowed heart (coronary) arteries, and are more likely to have worse heart function. In this trial, we aimed to test whether, in humans, giving high dose thiamine for three to five days to people before heart surgery (CABG) would improve the proliferation ability of CPCs. As part of the heart operation, a small part of the heart was taken to the laboratory, and the CPCs isolated and tested. 42 people (average age 65 years) were analysed in the study, and they were randomly given thiamine or a matching placebo (inactive tablet). We found that high dose thiamine did not improve the proliferation ability of CPCs. Thiamine did increase the proportion of CPCs with a cell marker called endoglin, which helps with developing new blood vessels. Thiamine also increased the power generated by isolated heart muscle, in a subgroup of people where we could test this. Overall, these results did not confirm our earlier studies. However, they encourage more lab based investigation into how CPCs work, considering another trial of thiamine in humans.

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-07-16
• Study Completion: 2018-09-17
• Last Update Posted: 15 November 2021

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 42

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).

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

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Resident cardiac progenitor cell proliferation as measured by BrdU assay[At time of coronary artery bypass grafting]

Secondary Outcome Measures

Name	Time	Method
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[At time of coronary artery bypass surgery];Level of activation of pentose phosphate pathway as measured by the level of transketolase in resident cardiac progenitor cells[At the time of coronary artery bypass surgery];Circulating thiamine levels[At the time of coronary artery bypass surgery.];Adverse effects assessment: headache, nausea, irritability, insomnia, rapid pulse, muscle weakness. These are assessed by interview and examination of vital signs.<br>[Day 3 (and day 4 if applicable) of being on study medication.]