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Inflammation Reduction by TREhalose AdminisTration (IR-TREAT)

Primary Purpose

Acute Coronary Syndrome

Status

Unknown status

Phase

Phase 2

Locations

Iran, Islamic Republic of

Study Type

Interventional

Intervention

Trehalose

Normal saline

About this trial

This is an interventional treatment trial for Acute Coronary Syndrome focused on measuring Acute Coronary Syndrome, Trehalose, Arterial inflammation, Autophagy

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept 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 > 2 times upper normal limit
Active infectious or febrile disease
Any type of malignancy
History of transplantation
Consumption of immunosuppressive drugs.

Sites / Locations

Ghaem Educational, Research and Treatment CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Trehalose

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

Arterial wall inflammation in the aorta and carotid arteries

This will be assessed using the 18F-FDG PET/CT imaging technique

Secondary Outcome Measures

Carotid intima-media thickness (cIMT)

This will be assessed using doppler sonography

Measuring beclin-1 to assess autophagy activation

Measuring high-sensitivity C-reactive protein (hs-CRP) to assess systemic inflammation

Measuring complete blood count (CBC) (Safety)

Assessing lipid profile (Safety)

Including triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)

Assessing glucose (Safety)

Fasting blood glucose (FBS)

Measuring thyroid-stimulating hormone (TSH) to assess thyroid function (Safety)

Measuring alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin (Bil) to assess liver function (Safety)

Measuring creatinine (Cr), urine (Ur) and blood urea nitrogen (BUN) to assess renal function (Safety)

Evaluating electrocardiogram (ECG) and heart rhythm to assess heart function (Safety)

Measuring creatinine phosphokinase (CPK) to detect muscle damage (Safety)

Full Information

NCT ID

NCT03700424

First Posted

October 3, 2018

Last Updated

September 17, 2020

Sponsor

Mashhad University of Medical Sciences

1. Study Identification

Unique Protocol Identification Number

NCT03700424

Brief Title

Inflammation Reduction by TREhalose AdminisTration

Acronym

IR-TREAT

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2020

Overall Recruitment Status

Unknown status

Study Start Date

August 20, 2020 (Actual)

Primary Completion Date

May 20, 2022 (Anticipated)

Study Completion Date

August 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Mashhad University of Medical Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Coronary Syndrome

Keywords

Acute Coronary Syndrome, Trehalose, Arterial inflammation, Autophagy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

This study will be performed double-blind

Allocation

Randomized

Enrollment

15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Trehalose

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Trehalose

Other Intervention Name(s)

Mycose

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Normal saline

Other Intervention Name(s)

Physiological saline, Isotonic saline

Intervention Description

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

Primary Outcome Measure Information:

Title

Arterial wall inflammation in the aorta and carotid arteries

Description

This will be assessed using the 18F-FDG PET/CT imaging technique

Time Frame

At the beginning and end of the intervention trial (Day 0 and week 12)

Secondary Outcome Measure Information:

Title

Carotid intima-media thickness (cIMT)

Description

This will be assessed using doppler sonography

Time Frame

At the beginning and end of the intervention trial (Day 0 and week 12)

Title

Measuring beclin-1 to assess autophagy activation

Time Frame

At the beginning and end of the intervention trial (Day 0 and week 12)

Title

Measuring high-sensitivity C-reactive protein (hs-CRP) to assess systemic inflammation

Time Frame

At the beginning and end of the intervention trial (Day 0 and week 12)

Title

Measuring complete blood count (CBC) (Safety)

Time Frame

At the beginning and end of the intervention trial (Day 0 and week 12)

Title

Assessing lipid profile (Safety)

Description

Including triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)

Time Frame

At the beginning and end of the intervention trial (Day 0 and week 12)

Title

Assessing glucose (Safety)

Description

Fasting blood glucose (FBS)

Time Frame

At the beginning and end of the intervention trial (Day 0 and week 12)

Title

Measuring thyroid-stimulating hormone (TSH) to assess thyroid function (Safety)

Time Frame

At the beginning and end of the intervention trial (Day 0 and week 12)

Title

Measuring alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin (Bil) to assess liver function (Safety)

Time Frame

At the beginning and end of the intervention trial (Day 0 and week 12)

Title

Measuring creatinine (Cr), urine (Ur) and blood urea nitrogen (BUN) to assess renal function (Safety)

Time Frame

At the beginning and end of the intervention trial (Day 0 and week 12)

Title

Evaluating electrocardiogram (ECG) and heart rhythm to assess heart function (Safety)

Time Frame

At the beginning and end of the intervention trial (Day 0 and week 12)

Title

Measuring creatinine phosphokinase (CPK) to detect muscle damage (Safety)

Time Frame

At the beginning and end of the intervention trial (Day 0 and week 12)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Amirhossien Sahebkar, PharmD, PhD

Phone

+985138002299

SahebkarA@mums.ac.ir

Facility Information:

Facility Name

Ghaem Educational, Research and Treatment Center

City

Mashhad

State/Province

Razavi Khorasan

ZIP/Postal Code

9919991766

Country

Iran, Islamic Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Amirhossein Sahebkar, PharmD, PhD

Phone

+989151221496

sahebkara@mums.ac.ir

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

22895665

Citation

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22445600

Citation

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Citation

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PubMed Identifier

26750103

Citation

Shao BZ, Han BZ, Zeng YX, Su DF, Liu C. The roles of macrophage autophagy in atherosclerosis. Acta Pharmacol Sin. 2016 Feb;37(2):150-6. doi: 10.1038/aps.2015.87. Epub 2016 Jan 11.

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Citation

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Citation

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Citation

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