Inflammation Reduction by TREhalose AdminisTration

Phase 2

• Conditions: Acute Coronary Syndrome
• Interventions: Drug: Trehalose; Drug: Normal saline

• Registration Number: NCT03700424
• Lead Sponsor: Mashhad University of Medical Sciences

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-10-03
• Study First Submitted QC: 2018-10-05
• Study First Posted: 2018-10-09
• Study Start: 2020-08-20
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-17
• Last Update Posted: 2020-09-21
• Primary Completion: 2022-05-20
• Study Completion: 2022-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 15

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Trehalose	Trehalose	Participants will be received intravenous trehalose infusion weekly (15 g/week) for a period of 12 weeks
Placebo	Normal saline	Participants will be received equal volume of normal saline weekly for a period of 12 weeks

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Measuring thyroid-stimulating hormone (TSH) to assess thyroid function (Safety)	At the beginning and end of the intervention trial (Day 0 and week 12)
Assessing glucose (Safety)	At the beginning and end of the intervention trial (Day 0 and week 12)	Fasting blood glucose (FBS)
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)
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 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)

Trial Locations

Locations (1)

Ghaem Educational, Research and Treatment Center; 🇮🇷 Mashhad, Razavi Khorasan, Iran, Islamic Republic of