Acute Coronary Syndrome
Conditions
Keywords
Acute Coronary Syndrome, Trehalose, Arterial inflammation, Autophagy
Brief summary
Arterial wall inflammation has been consistently suggested to serve a causal role in promoting atherosclerosis and predisposing to hard cardiovascular outcomes. Therefore, there is a global trend in the pharmaceutical industry to develop safe and effective anti-inflammatory agents that could lessen arterial wall inflammation and prevent its detrimental impact on atheroma growth and instability. To this end, autophagy has emerged as a key regulator of inflammation and dysfunctional autophagy machinery has been consistently reported as a contributing factor to atherosclerosis and inflammation. Trehalose, a natural disaccharide sugar found extensively among miscellaneous organisms, by preventing protein denaturation plays various protective roles against stress conditions. Numerous studies indicated trehalose's ability to induce macrophage autophagy-lysosomal biogenesis and reduce inflammation. Also, intravenous (IV) administration of trehalose showed beneficial effects in the reversal of atherosclerosis in atherosclerotic animals. Therefore, in this study, the investigators will explore the potential efficacy of IV trehalose administration on arterial inflammation by employing an positron emission tomography (PET) with 18F-labeled fluoro-2-deoxyglucose (18F-FDG) and computed tomography (18F-FDG PET/CT) technique which noninvasively characterizes vascular inflammation and atherosclerosis.
Interventions
DRUGTrehalose
Trehalose is a natural disaccharide sugar found extensively among miscellaneous organisms including bacteria, plants, insects, yeast, fungi, and invertebrates. By preventing protein denaturation, it plays various protective roles against stress conditions such as heat, freeze, oxidation, desiccation and dehydration. Owing to this capacity, trehalose is an FDA-approved pharmaceutical excipient that is used as a stabilizer in numerous medicines including parenteral products. In this study, all injections will be conducted by a trained nurse in the presence of a specialist physician at a duration of 45-90 minutes.
DRUGNormal saline
A solution of 0.90% w/v of sodium chloride (NaCl) in water
Sponsors
Mashhad University of Medical Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This study will be performed double-blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Men and women aged between 18-55 years * Having a history of acute coronary syndrome * Having a baseline high-sensitivity C-reactive protein (hs-CRP) of ≥ 2mg/L * Willingness to participate in the trials.
Exclusion criteria
* Lactation or breastfeeding * Diabetes mellitus * Nephrotic syndrome or Estimated Glomerular Filtration Rate (eGFR) \< 30/mL/min/1.73m2 * Active or recurrent hepatic disease or/and alanine aminotransferase (ALT)/aspartate aminotransferase (AST) (ALT/AST) of \> 3 times upper normal limit or total bilirubin of \> 2 times upper normal limit * Active infectious or febrile disease * Any type of malignancy * History of transplantation * Consumption of immunosuppressive drugs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Arterial wall inflammation in the aorta and carotid arteries | At the beginning and end of the intervention trial (Day 0 and week 12) | This will be assessed using the 18F-FDG PET/CT imaging technique |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measuring beclin-1 to assess autophagy activation | At the beginning and end of the intervention trial (Day 0 and week 12) | — |
| Measuring high-sensitivity C-reactive protein (hs-CRP) to assess systemic inflammation | At the beginning and end of the intervention trial (Day 0 and week 12) | — |
| Measuring complete blood count (CBC) (Safety) | At the beginning and end of the intervention trial (Day 0 and week 12) | — |
| Assessing lipid profile (Safety) | At the beginning and end of the intervention trial (Day 0 and week 12) | Including triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) |
| Assessing glucose (Safety) | At the beginning and end of the intervention trial (Day 0 and week 12) | Fasting blood glucose (FBS) |
| Carotid intima-media thickness (cIMT) | At the beginning and end of the intervention trial (Day 0 and week 12) | This will be assessed using doppler sonography |
| Measuring alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin (Bil) to assess liver function (Safety) | At the beginning and end of the intervention trial (Day 0 and week 12) | — |
| Measuring creatinine (Cr), urine (Ur) and blood urea nitrogen (BUN) to assess renal function (Safety) | At the beginning and end of the intervention trial (Day 0 and week 12) | — |
| Evaluating electrocardiogram (ECG) and heart rhythm to assess heart function (Safety) | At the beginning and end of the intervention trial (Day 0 and week 12) | — |
| Measuring creatinine phosphokinase (CPK) to detect muscle damage (Safety) | At the beginning and end of the intervention trial (Day 0 and week 12) | — |
| Measuring thyroid-stimulating hormone (TSH) to assess thyroid function (Safety) | At the beginning and end of the intervention trial (Day 0 and week 12) | — |
Countries
Iran
Contacts
Primary ContactAmirhossien Sahebkar, PharmD, PhD
Outcome results
None listed