Ignite Creation Date:
2024-10-26 @ 3:43 PM
Last Modification Date:
2024-10-26 @ 3:43 PM
Study NCT ID:
NCT06656442
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-10-21
Brief Title:
The Effect of Trimetazidine on the Clinical Outcome of Acute Ischemic Stroke Patients
Sponsor:
None
Organization:
None
Study Overview
Official Title:
The Effect of Trimetazidine on the Clinical Outcome of Acute Ischemic Stroke Patients
Status:
RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The investigators need to test the effect of Trimetazidine on the pro-inflammatory marker Interleukin - 18 NIHSS score and mRs score of acute ischemic stroke patients
Detailed Description:
Trimetazidine is a well-known anti-anginal drug that exerts its effect by converting the cells metabolism from fatty acid oxidation to glucose oxidation This is contrary to what occurs during a stroke event in which the cells metabolism is shifted to fatty acid metabolism It also improves the activity of pyruvate dehydrogenase the enzyme that allows the entry of pyruvate from the cytosol into the mitochondria for subsequent oxidation in the Krebs cycle Therefore attenuating lactic acid production controlling intracellular acidosis and calcium ion overload thus conserving valuable ATP stores to meet energy requirements and preventing the occurrence of further ischemia Clinical reports indicate that trimetazidine restores energy homeostasis and attenuates free radical generation to exhibit benefits in ischemia and angina pectoris
An increasing number of studies have focused on the effect of Trimetazidine on myocardial IR injury and some studies have proposed possible hypotheses Trimetazidine protects against myocardial IR injury and is presumed to be related to autophagy apoptosis and oxidative stress which are all pathways in stroke
An in vitro study proving the role of Trimetazidine in apoptosis found that trimetazidine protected muscle cells against starvation or inflammation-induced atrophy by inhibiting protein degradation and inducing autophagy It has recently been shown to ameliorate lipopolysaccharide LPS-induced cardiomyocyte pyroptosis which plays an important role in the development of muscle atrophy by promoting neutrophil migration to cardiac tissue It was shown that Trimetazidine mitigated the mRNA expression of pyroptosis-related molecules including NLRP3 Caspase-1 and GSDMD25 In another in vitro study it was found that TMZ reduced the myocardial infarct size and decreased the expression of TLR4 MyD88 phospho-NF-κB p65 and the NLRP3 inflammasome
Furthermore a study assessing the effect of TMZ on cerebral IR injury proved that it reduced infarct volume compared with the vehicle-treated reperfused animals and significantly decreased the percentage of brain swelling in the TMZ-treated groups
Trimetazidine in a clinical study added to the standard of care with or without interventional andor surgical reperfusion reduced oxidative stress endothelial dysfunction inflammation and major acute cardiovascular events whereas in patients with chronic coronary syndrome TMZ decreased oxidative stress and readmission for ACS and heart failure
Moreover there is a recent clinical trial that has proven that Trimetazidine significantly reduced the serum levels of interleukin - 18 in patients with acute viral myocarditis compared to the control group
This makes it possible to detect the severity of the stroke event by measuring the serum levels of interleukin - 18 It is a pro-inflammatory cytokine that is encoded by the IL-18 gene in humans It is likely to be the first line of immune defense for the brain primarily secreted by macrophage cells and mononuclear cells in humans It is initially expressed as the inactive precursor pro-IL-18 It is then converted into an active form by proteolytic cleavage mainly by the cysteine protease caspase-1 which is also known as IL-1B converting enzyme ICE
Some researchers have proposed the hypothesis that a pro-inflammatory profile induced by increased IL-18 levels creates a prothrombotic and pro-atherosclerotic environment which may eventually contribute to stroke in older people These results are consistent with the results of a meta-analysis study which proved that there is a significant association between IL-18 level and NIHSS scores that makes it a strong tool for reflecting the severity of stroke and for predicting the prognosis
An increasing number of studies have focused on the effect of Trimetazidine on myocardial IR injury and some studies have proposed possible hypotheses Trimetazidine protects against myocardial IR injury and is presumed to be related to autophagy apoptosis and oxidative stress which are all pathways in stroke
An in vitro study proving the role of Trimetazidine in apoptosis found that trimetazidine protected muscle cells against starvation or inflammation-induced atrophy by inhibiting protein degradation and inducing autophagy It has recently been shown to ameliorate lipopolysaccharide LPS-induced cardiomyocyte pyroptosis which plays an important role in the development of muscle atrophy by promoting neutrophil migration to cardiac tissue It was shown that Trimetazidine mitigated the mRNA expression of pyroptosis-related molecules including NLRP3 Caspase-1 and GSDMD25 In another in vitro study it was found that TMZ reduced the myocardial infarct size and decreased the expression of TLR4 MyD88 phospho-NF-κB p65 and the NLRP3 inflammasome
Furthermore a study assessing the effect of TMZ on cerebral IR injury proved that it reduced infarct volume compared with the vehicle-treated reperfused animals and significantly decreased the percentage of brain swelling in the TMZ-treated groups
Trimetazidine in a clinical study added to the standard of care with or without interventional andor surgical reperfusion reduced oxidative stress endothelial dysfunction inflammation and major acute cardiovascular events whereas in patients with chronic coronary syndrome TMZ decreased oxidative stress and readmission for ACS and heart failure
Moreover there is a recent clinical trial that has proven that Trimetazidine significantly reduced the serum levels of interleukin - 18 in patients with acute viral myocarditis compared to the control group
This makes it possible to detect the severity of the stroke event by measuring the serum levels of interleukin - 18 It is a pro-inflammatory cytokine that is encoded by the IL-18 gene in humans It is likely to be the first line of immune defense for the brain primarily secreted by macrophage cells and mononuclear cells in humans It is initially expressed as the inactive precursor pro-IL-18 It is then converted into an active form by proteolytic cleavage mainly by the cysteine protease caspase-1 which is also known as IL-1B converting enzyme ICE
Some researchers have proposed the hypothesis that a pro-inflammatory profile induced by increased IL-18 levels creates a prothrombotic and pro-atherosclerotic environment which may eventually contribute to stroke in older people These results are consistent with the results of a meta-analysis study which proved that there is a significant association between IL-18 level and NIHSS scores that makes it a strong tool for reflecting the severity of stroke and for predicting the prognosis
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None