Inflammation Reduction by TREhalose AdminisTration

Study Overview
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Brief Summary
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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.

Official Title
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The Use of Intravenous Trehalose to Reduce Vascular Inflammation in Acute Coronary Syndrome

Conditions
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Acute Coronary Syndrome

Intervention / Treatment
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* Drug: Trehalose
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trehalose<br>Participants will be received intravenous trehalose infusion weekly (15 g/week) for a period of 12 weeks | Drug: Trehalose<br>* 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.<br>* Other names: Mycose;|
| Placebo Comparator: Placebo<br>Participants will be received equal volume of normal saline weekly for a period of 12 weeks | Drug: Normal saline<br>* A solution of 0.90% w/v of sodium chloride (NaCl) in water<br>* Other names: Isotonic saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arterial wall inflammation in the aorta and carotid arteries | This will be assessed using the 18F-FDG PET/CT imaging technique | At the beginning and end of the intervention trial (Day 0 and week 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Carotid intima-media thickness (cIMT) | This will be assessed using doppler sonography | At the beginning and end of the intervention trial (Day 0 and week 12) | 
| 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) | Including triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) | At the beginning and end of the intervention trial (Day 0 and week 12) | 
| Assessing glucose (Safety) | Fasting blood glucose (FBS) | 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) | 
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Coronary Syndrome, Trehalose, Arterial inflammation, Autophagy