JMIR Publications

ABSTRACT

Introduction Inflammation plays a key role in the pathophysiology of coronary heart disease (CHD) and its acute manifestation-acute coronary syndrome (ACS). Ageing is associated with a decline of the immune system, a process known as immunosenescence. This is characterised by an increase in highly pro-inflammatory T cells that are involved in CHD progression, plaque destabilisation and myocardial ischemia-reperfusion injury. Telomere dysfunction has been implicated in immunosenescence of T-lymphocytes. Telomerase is the enzyme responsible for maintaining telomeres during cell divisions. It has a protective effect on cells under oxidative stress and helps regulate flow-mediated dilatation in microvasculature. The TACTIC trial will investigate whether a telomerase activator (TA-65MD®) can reduce the proportion of senescent T cells in patients with ACS with confirmed CHD. It will also assess the effect of TA-65MD® on decreasing telomere shortening, reducing oxidative stress and improving endothelial function. Methods The study was designed as a single centre, randomised, double-blind, parallel group, placebo-controlled phase II trial. Recruitment started in January 2019. Ninety patients aged ≥ 65 with treated ACS who have had CHD confirmed by angiography will be enrolled. They will be randomised to either TA-65MD® oral therapy (8mg BD) or placebo taken for 12 months. The primary outcome is the effect on immunosenescence determined by a decrease in the proportion of CD8+ TEMRA cells at 12 months. Secondary outcomes include leukocyte telomere length, endothelial function, cardiac function as measured by echocardiography and NT-proBNP, systemic inflammation, oxidative stress and telomerase activity. Discussion This pilot trial in older patients with CHD, will explore outcomes not previously investigated outside in-vitro or pre-clinical models. The robust design ensures that bias has been minimised. Should the results indicate reduced frequency of immunosenescent CD8+ T cells and improvements in telomere length as well as endothelial function, we will plan a larger, multi-centre trial in patients to determine if TA-65MD® is beneficial in the treatment of CHD.