Inflammation Reduction by TREhalose AdminisTration

NCT ID: NCT03700424

Last Updated: 2020-09-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-08-20

Study Completion Date

2022-08-31

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.

Detailed Description

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Conditions

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Acute Coronary Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
This study will be performed double-blind

Study Groups

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Trehalose

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

Group Type EXPERIMENTAL

Trehalose

Intervention Type DRUG

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.

Placebo

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

Group Type PLACEBO_COMPARATOR

Normal saline

Intervention Type DRUG

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

Interventions

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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.

Intervention Type DRUG

Normal saline

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

Intervention Type DRUG

Other Intervention Names

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Mycose Physiological saline Isotonic saline

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mashhad University of Medical Sciences

OTHER

Sponsor Role lead

Responsible Party

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Amirhossein Sahebkar

Assistant Professor at Mashhad University of Medical Sciences

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Ghaem Educational, Research and Treatment Center

Mashhad, Razavi Khorasan Province, Iran

Site Status RECRUITING

Countries

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Iran

Central Contacts

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Amirhossien Sahebkar, PharmD, PhD

Role: CONTACT

+985138002299

Facility Contacts

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Amirhossein Sahebkar, PharmD, PhD

Role: primary

+989151221496

References

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Libby P. Inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol. 2012 Sep;32(9):2045-51. doi: 10.1161/ATVBAHA.108.179705.

Reference Type BACKGROUND
PMID: 22895665 (View on PubMed)

Libby P, Hansson GK. Taming Immune and Inflammatory Responses to Treat Atherosclerosis. J Am Coll Cardiol. 2018 Jan 16;71(2):173-176. doi: 10.1016/j.jacc.2017.10.081. No abstract available.

Reference Type BACKGROUND
PMID: 29325641 (View on PubMed)

Liao X, Sluimer JC, Wang Y, Subramanian M, Brown K, Pattison JS, Robbins J, Martinez J, Tabas I. Macrophage autophagy plays a protective role in advanced atherosclerosis. Cell Metab. 2012 Apr 4;15(4):545-53. doi: 10.1016/j.cmet.2012.01.022. Epub 2012 Mar 22.

Reference Type BACKGROUND
PMID: 22445600 (View on PubMed)

Maiuri MC, Grassia G, Platt AM, Carnuccio R, Ialenti A, Maffia P. Macrophage autophagy in atherosclerosis. Mediators Inflamm. 2013;2013:584715. doi: 10.1155/2013/584715. Epub 2013 Jan 21.

Reference Type BACKGROUND
PMID: 23401644 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26750103 (View on PubMed)

Iwatsuka R, Matsue Y, Yonetsu T, O'uchi T, Matsumura A, Hashimoto Y, Hirao K. Arterial inflammation measured by 18F-FDG-PET-CT to predict coronary events in older subjects. Atherosclerosis. 2018 Jan;268:49-54. doi: 10.1016/j.atherosclerosis.2017.11.016. Epub 2017 Nov 21.

Reference Type BACKGROUND
PMID: 29175654 (View on PubMed)

Chrapko BE, Chrapko M, Nocun A, Stefaniak B, Zubilewicz T, Drop A. Role of 18F-FDG PET/CT in the diagnosis of inflammatory and infectious vascular disease. Nucl Med Rev Cent East Eur. 2016;19(1):28-36. doi: 10.5603/NMR.2016.0006.

Reference Type BACKGROUND
PMID: 26841377 (View on PubMed)

Menezes LJ, Kotze CW, Hutton BF, Endozo R, Dickson JC, Cullum I, Yusuf SW, Ell PJ, Groves AM. Vascular inflammation imaging with 18F-FDG PET/CT: when to image? J Nucl Med. 2009 Jun;50(6):854-7. doi: 10.2967/jnumed.108.061432. Epub 2009 May 14.

Reference Type BACKGROUND
PMID: 19443587 (View on PubMed)

Chen Q, Haddad GG. Role of trehalose phosphate synthase and trehalose during hypoxia: from flies to mammals. J Exp Biol. 2004 Aug;207(Pt 18):3125-9. doi: 10.1242/jeb.01133.

Reference Type BACKGROUND
PMID: 15299033 (View on PubMed)

Castillo K, Nassif M, Valenzuela V, Rojas F, Matus S, Mercado G, Court FA, van Zundert B, Hetz C. Trehalose delays the progression of amyotrophic lateral sclerosis by enhancing autophagy in motoneurons. Autophagy. 2013 Sep;9(9):1308-20. doi: 10.4161/auto.25188. Epub 2013 Jun 6.

Reference Type BACKGROUND
PMID: 23851366 (View on PubMed)

Mardones P, Rubinsztein DC, Hetz C. Mystery solved: Trehalose kickstarts autophagy by blocking glucose transport. Sci Signal. 2016 Feb 23;9(416):fs2. doi: 10.1126/scisignal.aaf1937.

Reference Type BACKGROUND
PMID: 26905424 (View on PubMed)

Sergin I, Evans TD, Zhang X, Bhattacharya S, Stokes CJ, Song E, Ali S, Dehestani B, Holloway KB, Micevych PS, Javaheri A, Crowley JR, Ballabio A, Schilling JD, Epelman S, Weihl CC, Diwan A, Fan D, Zayed MA, Razani B. Exploiting macrophage autophagy-lysosomal biogenesis as a therapy for atherosclerosis. Nat Commun. 2017 Jun 7;8:15750. doi: 10.1038/ncomms15750.

Reference Type BACKGROUND
PMID: 28589926 (View on PubMed)

van der Valk FM, Bekkering S, Kroon J, Yeang C, Van den Bossche J, van Buul JD, Ravandi A, Nederveen AJ, Verberne HJ, Scipione C, Nieuwdorp M, Joosten LA, Netea MG, Koschinsky ML, Witztum JL, Tsimikas S, Riksen NP, Stroes ES. Oxidized Phospholipids on Lipoprotein(a) Elicit Arterial Wall Inflammation and an Inflammatory Monocyte Response in Humans. Circulation. 2016 Aug 23;134(8):611-24. doi: 10.1161/CIRCULATIONAHA.116.020838. Epub 2016 Aug 5.

Reference Type BACKGROUND
PMID: 27496857 (View on PubMed)

van der Valk FM, Verweij SL, Zwinderman KA, Strang AC, Kaiser Y, Marquering HA, Nederveen AJ, Stroes ES, Verberne HJ, Rudd JH. Thresholds for Arterial Wall Inflammation Quantified by 18F-FDG PET Imaging: Implications for Vascular Interventional Studies. JACC Cardiovasc Imaging. 2016 Oct;9(10):1198-1207. doi: 10.1016/j.jcmg.2016.04.007. Epub 2016 Sep 14.

Reference Type BACKGROUND
PMID: 27639759 (View on PubMed)

Other Identifiers

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964334

Identifier Type: -

Identifier Source: org_study_id

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