Dataset Information

Telomerase Activation to Reverse Immunosenescence in Elderly Patients With Acute Coronary Syndrome: Protocol for a Randomized Pilot Trial.

ABSTRACT: BACKGROUND:Inflammation plays a key role in the pathophysiology of coronary heart disease (CHD) and its acute manifestation, acute coronary syndrome (ACS). Aging is associated with a decline of the immune system, a process known as immunosenescence. This is characterized by an increase in highly proinflammatory T cells that are involved in CHD progression, plaque destabilization, 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 dilation in microvasculature. OBJECTIVE:The TACTIC (Telomerase ACTivator to reverse Immunosenescence in Acute Coronary Syndrome) 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-center, randomized, double-blind, parallel-group, placebo-controlled phase II trial. Recruitment started in January 2019. A total of 90 patients, aged 65 years or older, with treated ACS who have had CHD confirmed by angiography will be enrolled. They will be randomized to one of two groups: TA-65MD oral therapy (8 mg twice daily) or placebo taken for 12 months. The primary outcome is the effect on immunosenescence determined by a decrease in the proportion of CD8+ TEMRA (T effector memory cells re-expressing CD45RA [CD45 expressing exon A]) cells at 12 months. Secondary outcomes include leukocyte telomere length, endothelial function, cardiac function as measured by echocardiography and NT-proBNP (N-terminal fragment of the prohormone brain-type natriuretic peptide), systemic inflammation, oxidative stress, and telomerase activity. RESULTS:The study received National Health Service (NHS) ethics approval on August 9, 2018; Medicines and Healthcare products Regulatory Agency approval on October 19, 2018; and NHS Health Research Authority approval on October 22, 2018. The trial began recruiting participants in January 2019 and completed recruitment in March 2020; the trial is due to report results in 2021. CONCLUSIONS:This pilot trial in older patients with CHD will explore outcomes not previously investigated outside in vitro or preclinical models. The robust design ensures that bias has been minimized. Should the results indicate reduced frequency of immunosenescent CD8+ T cells as well as improvements in telomere length and endothelial function, we will plan a larger, multicenter trial in patients to determine if TA-65MD is beneficial in the treatment of CHD in elderly patients. TRIAL REGISTRATION:ISRCTN Registry ISRCTN16613292; http://www.isrctn.com/ISRCTN16613292 and European Union Drug Regulating Authorities Clinical Trials Database (EudraCT), European Union Clinical Trials Register 2017-002876-26; https://tinyurl.com/y4m2so8g. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):DERR1-10.2196/19456.

SUBMITTER: Maier R

PROVIDER: S-EPMC7542409 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Telomerase Activation to Reverse Immunosenescence in Elderly Patients With Acute Coronary Syndrome: Protocol for a Randomized Pilot Trial.

Maier Rebecca R Bawamia Bilal B Bennaceur Karim K Dunn Sarah S Marsay Leanne L Amoah Roland R Kasim Adetayo A Filby Andrew A Austin David D Hancock Helen H Spyridopoulos Ioakim I

JMIR research protocols 20200923 9

<h4>Background</h4>Inflammation plays a key role in the pathophysiology of coronary heart disease (CHD) and its acute manifestation, acute coronary syndrome (ACS). Aging is associated with a decline of the immune system, a process known as immunosenescence. This is characterized by an increase in highly proinflammatory T cells that are involved in CHD progression, plaque destabilization, and myocardial ischemia-reperfusion injury. Telomere dysfunction has been implicated in immunosenescence of T ...[more]

PMID: 32965237

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Project description:Background and Objectives: Nearly 23% of elderly patients hospitalized due to acute coronary syndrome have reduced muscle strength. It is assumed that these patients would better benefit from a complex training-a combination of endurance, strength, balance, coordination, and flexibility-in order to reduce the loss of muscle strength and mass and improve functional capacity. The aim of this study was to assess the effectiveness and safety of two different complementary resistance and balance training programs during short-term cardiac rehabilitation (CR) in elderly patients after a percutaneous or surgical intervention due to acute coronary syndrome. Materials and Methods: This randomized controlled trial was conducted from January 2020 to February 2021 in one Lithuanian rehabilitation hospital. A total of 63 participants who met the inclusion criteria were randomly assigned to three groups (at the ratio of 1:1:1): control (CG, n = 19), intervention 1 (IG-1, n = 26), and intervention 2 (IG-2, n = 18). All the patients attended a usual inpatient CR program of a mean duration of 18.7 ± 1.7 days, while the patients assigned to the intervention groups (IG-1 and IG-2) additionally received different resistance and balance training programs three days a week. Functional capacity, with 6-minute walk test (6MWT) and cardiopulmonary exercise testing (CPET), as well as physical performance, with the short physical performance battery (SPPB) test and one repetition maximum test (1RM) for leg press, were assessed at baseline and after CR. Results: The mean age of the participants was 72.9 ± 5.5 years; 73% were men. All parameters of functional capacity and physical performance improved significantly after CR (p < 0.05), except for peak VO2 that improved only in the IG-1. Comparison of CR effectiveness among the groups revealed no significant differences. Conclusions: All three rehabilitation programs were safe and well tolerated by elderly patients aged ≥65 years as well as improved functional capacity (6-minute walk distance and peak workload) and physical performance (SPPB and 1RM). Complementary resistance and balance training with traditional physical therapy means and exercises with mechanical devices did not show greater benefits for the results of physical performance compared with the usual CR program.

Project description:BackgroundAcute coronary syndrome (ACS) is linked to a range of in-hospital complications, and age is recognized as risk factor for adverse events. Discrepancies between physiological and chronological age are explained by frailty. However, the relationship between frailty and in-hospital complications is not clear.MethodsAssessment of frailty in patients was carried out using the FRAIL scale. In-hospital complications assessed included, bleeding, infection, arrhythmia, acute kidney injury (AKI), delirium, stroke/transient ischemic attack (TIA), liver injury, hypoglycemia, length of stay in the cardiac care unit (CCU).ResultsOf the 174 patients, frailty was identified in 39.1% and pre-frailty in 29.9%. Frailty was associated with a higher incidence of all types of bleeding (frail vs. robust: 45.5% vs. 16.7%, P < 0.001) and infection (54.4% vs. 11.1%, P < 0.001), including pneumonia/lower respiratory tract infections (LRTI) and urinary tract infections (UTI). Incidence of antibiotic therapy (52.9% vs. 13.0%, P < 0.001), atrial fibrillation (AF) (47.1% vs. 9.3%, P < 0.001), AKI (57.3% vs. 20.4%, P < 0.001), delirium (52.9% vs. 3.7%, P < 0.001), liver injury, were higher in frail patients (17.6% vs. 0, P = 0.001), whilst their length of stay in the CCU was longer (4 days (2-6.5) vs. 2 days (2-3), P < 0.001). Infections, pneumonia/LRTI, antibiotic therapy during hospitalization, the incidence of AF and liver injury were more often in patients with pre-frailty compared to the robust group. After adjustment for potential confounders, frailty remained independently associated with an increased risk of infection (OR: 3.3 [1.6-7.0]), including pneumonia/LRTI (OR: 2.5 [1.1-5.8]) and UTI (OR: 4.8 [1.8-12.5]). Frail individuals had an increased requirement for antibiotic therapy (OR: 3.9 [1.9-8.1]), and greater risk of AF (OR: 3.5 [1.3-9.3]), AKI (OR: 2.6 [1.2-5.3]) delirium (OR: 11.7 [4.8-28.7]), as well as having to stay longer in the CCU (> 3 days) (OR: 3.7 [1.9-7.3]).ConclusionsFrailty was associated with an increased risk of numerous in-hospital complications in elderly patients who had been hospitalized with ACS.

Project description:BackgroundOptimum management after an acute coronary syndrome (ACS) requires considerable patient engagement/activation. Religious practices permeate people's lives and may influence engagement in their healthcare. Little is known about the relationship between religiosity and patient activation.ObjectiveTo examine the association between religiosity and patient activation in hospital survivors of an ACS.DesignSecondary analysis using baseline data from Transitions, Risks, and Actions in Coronary Events: Center for Outcomes Research and Education (TRACE-CORE) Study.ParticipantsA total of 2067 patients hospitalized for an ACS at six medical centers in Central Massachusetts and Georgia (2011-2013).Main measuresStudy participants self-reported three items assessing religiosity-strength and comfort from religion, making petition prayers, and awareness of intercessory prayers for health. Patient activation was assessed using the 6-item Patient Activation Measure (PAM-6). Participants were categorized as either having low (levels 1 and 2) or high (levels 3 and 4) activation.ResultsThe mean age of study participants was 61 years, 33% were women, and 81% were non-Hispanic White. Approximately 85% derived strength and comfort from religion, 61% prayed for their health, and 89% received intercessory prayers for their health. Overall, 58% had low activation. Reports of a great deal (aOR, 2.02; 95% CI, 1.44-2.84), and little/some (aOR, 1.45; 95% CI, 1.07-1.98) strength and comfort from religion were associated with high activation, as were receipt of intercessions (aOR, 1.48; 95% CI, 1.07-2.05). Praying for one's health was associated with low activation (aOR, 0.78; 95% CI, 0.61-0.99).ConclusionsMost ACS survivors acknowledge religious practices toward their recovery. Strength and comfort from religion and intercessory prayers for health were associated with high patient activation. Petition prayers for health were associated with low activation. Healthcare providers should use knowledge about patient's religiosity to enhance patient engagement in their care.

Dataset Information

Telomerase Activation to Reverse Immunosenescence in Elderly Patients With Acute Coronary Syndrome: Protocol for a Randomized Pilot Trial.

Publications

Telomerase Activation to Reverse Immunosenescence in Elderly Patients With Acute Coronary Syndrome: Protocol for a Randomized Pilot Trial.

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