Mycose AdminiStration for HealIng Alzheimer NEuropathy (MASHIANE)

NCT ID: NCT04663854

Last Updated: 2020-12-11

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

PHASE1

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-08-20

Study Completion Date

2022-08-20

Brief Summary

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Alzheimer's disease (AD) is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills, and, eventually, the ability to function independently. Despite the significant effort to understand the basic biology of the disease and pharmaceutical advances to develop drugs, there is no effective therapy available to treat AD or slow the disease progression.

β-amyloid accumulation outside brain cells and abnormal accumulations of tau protein inside neurons are taught to be two main changes in the brain that lead to AD. Progressive accumulation of β-amyloid interferes with the neuron-to-neuron communication at synapses, contributing to neural cell death. Also, tau tangles block the transport of nutrients and other essential molecules into the neurons. Many molecules have been shown to inhibit amyloid aggregation. The anti-amyloidogenic activity of trehalose was confirmed in both in vitro and in vivo studies and its inhibitory effects on β-amyloid formation in AD have also been demonstrated. Trehalose is a non-toxic disaccharide and no dose-dependent adverse effects were seen in any of the safety studies. It can act as a chemical chaperone and stabilizes the natively folded structure of protein and also trehalose has been identified as an autophagy inducer and promotes the clearance of aggregated proteins. Therefore, trehalose could be a valuable candidate for the treatment and prevention of amyloid-related disease. Based on the proposed hypothesis, this study aim to investigate the potential efficacy of trehalose administration in patients with AD.

Detailed Description

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Purpose of the study: A randomized, triple-blind, pilot clinical trial has been designed to evaluate the effectiveness of trehalose on reducing the symptoms in AD patients. Study intervention: twenty patients with Alzheimer's disease were randomly divided into an intervention and a control group. Trehalose will be administrated intravenously (15 g/week) for 12 weeks in the intervention group and the control group will be received normal saline as a placebo.

Conditions

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Alzheimer Disease

Keywords

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Alzheimer Disease Trehalose Clinical Trial Autophagy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Trehalose

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

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.

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

Other Intervention Names

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Mycose

Eligibility Criteria

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Inclusion Criteria

* Mini-Mental State Examination (MMSE) score range from 10 to 23
* Not having other cognitive disorders

Exclusion Criteria

* MMSE score higher than 23 or lower than 10
* The presence of other cognitive disorders which will be evaluated by clinical assessment and brain imaging
* The presence of factors affecting cognitive impairment such as depression
* Vascular dementia and Lewy body dementia
* Previous history of head trauma
* Use of alcohol and other drugs that affect cognitive functioning
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

Associate 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, PhD

Role: CONTACT

Phone: +985138002299

Email: [email protected]

Facility Contacts

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Amirhossein Sahebkar, PharmD, PhD

Role: primary

References

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Prince M, Comas-Herrera A, Knapp M, Guerchet M, Karagiannidou M. World Alzheimer report 2016: improving healthcare for people living with dementia: coverage, quality and costs now and in the future.

Reference Type BACKGROUND

Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement. 2013 Jan;9(1):63-75.e2. doi: 10.1016/j.jalz.2012.11.007.

Reference Type BACKGROUND
PMID: 23305823 (View on PubMed)

Alzheimer's Association. 2015 Alzheimer's disease facts and figures. Alzheimers Dement. 2015 Mar;11(3):332-84. doi: 10.1016/j.jalz.2015.02.003.

Reference Type BACKGROUND
PMID: 25984581 (View on PubMed)

Cohen FE, Kelly JW. Therapeutic approaches to protein-misfolding diseases. Nature. 2003 Dec 18;426(6968):905-9. doi: 10.1038/nature02265.

Reference Type BACKGROUND
PMID: 14685252 (View on PubMed)

Teplow DB. Structural and kinetic features of amyloid beta-protein fibrillogenesis. Amyloid. 1998 Jun;5(2):121-42. doi: 10.3109/13506129808995290.

Reference Type BACKGROUND
PMID: 9686307 (View on PubMed)

Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, Szoeke C, Macaulay SL, Martins R, Maruff P, Ames D, Rowe CC, Masters CL; Australian Imaging Biomarkers and Lifestyle (AIBL) Research Group. Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study. Lancet Neurol. 2013 Apr;12(4):357-67. doi: 10.1016/S1474-4422(13)70044-9. Epub 2013 Mar 8.

Reference Type BACKGROUND
PMID: 23477989 (View on PubMed)

Izmitli A, Schebor C, McGovern MP, Reddy AS, Abbott NL, de Pablo JJ. Effect of trehalose on the interaction of Alzheimer's Abeta-peptide and anionic lipid monolayers. Biochim Biophys Acta. 2011 Jan;1808(1):26-33. doi: 10.1016/j.bbamem.2010.09.024. Epub 2010 Oct 1.

Reference Type BACKGROUND
PMID: 20920466 (View on PubMed)

Du J, Liang Y, Xu F, Sun B, Wang Z. Trehalose rescues Alzheimer's disease phenotypes in APP/PS1 transgenic mice. J Pharm Pharmacol. 2013 Dec;65(12):1753-6. doi: 10.1111/jphp.12108. Epub 2013 Aug 5.

Reference Type BACKGROUND
PMID: 24236985 (View on PubMed)

Arora A, Ha C, Park CB. Inhibition of insulin amyloid formation by small stress molecules. FEBS Lett. 2004 Apr 23;564(1-2):121-5. doi: 10.1016/S0014-5793(04)00326-6.

Reference Type BACKGROUND
PMID: 15094052 (View on PubMed)

Tanaka M, Machida Y, Niu S, Ikeda T, Jana NR, Doi H, Kurosawa M, Nekooki M, Nukina N. Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease. Nat Med. 2004 Feb;10(2):148-54. doi: 10.1038/nm985. Epub 2004 Jan 18.

Reference Type BACKGROUND
PMID: 14730359 (View on PubMed)

Yoshizane C, Mizote A, Yamada M, Arai N, Arai S, Maruta K, Mitsuzumi H, Ariyasu T, Ushio S, Fukuda S. Glycemic, insulinemic and incretin responses after oral trehalose ingestion in healthy subjects. Nutr J. 2017 Feb 6;16(1):9. doi: 10.1186/s12937-017-0233-x.

Reference Type BACKGROUND
PMID: 28166771 (View on PubMed)

Richards AB, Krakowka S, Dexter LB, Schmid H, Wolterbeek AP, Waalkens-Berendsen DH, Shigoyuki A, Kurimoto M. Trehalose: a review of properties, history of use and human tolerance, and results of multiple safety studies. Food Chem Toxicol. 2002 Jul;40(7):871-98. doi: 10.1016/s0278-6915(02)00011-x.

Reference Type BACKGROUND
PMID: 12065209 (View on PubMed)

Ohtake S, Wang YJ. Trehalose: current use and future applications. J Pharm Sci. 2011 Jun;100(6):2020-53. doi: 10.1002/jps.22458. Epub 2011 Feb 18.

Reference Type BACKGROUND
PMID: 21337544 (View on PubMed)

Other Identifiers

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971659

Identifier Type: -

Identifier Source: org_study_id