IR-TREAT: Inflammation Reduction by TREhalose AdminisTration

Sponsor

Mashhad University of Medical Sciences (Other)

Overall Status

Recruiting

CT.gov ID

NCT03700424

Collaborator

(none)

Enrollment

Location

Arms

23.4

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Coronary Syndrome	Drug: Trehalose Drug: Normal saline	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

15 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

This study will be performed double-blind

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 20, 2020

Anticipated Primary Completion Date :

May 20, 2022

Anticipated Study Completion Date :

Aug 1, 2022

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Trehalose

Participants will be received intravenous trehalose infusion weekly (15 g/week) for a period of 12 weeks

Drug: Trehalose

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.

Other Names:

Mycose

Placebo Comparator: Placebo

Participants will be received equal volume of normal saline weekly for a period of 12 weeks

Drug: Normal saline

A solution of 0.90% w/v of sodium chloride (NaCl) in water

Other Names:

Physiological saline

Isotonic saline

Outcome Measures

Primary Outcome Measures

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

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)
Assessing glucose (Safety) [At the beginning and end of the intervention trial (Day 0 and week 12)]
Fasting blood glucose (FBS)
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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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