Mycose AdminiStration for HealIng Alzheimer NEuropathy (MASHIANE)

NCT04663854 | Unknown Phase 1

• 1 other identifier: 971659
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alzheimer Disease

Keywords

Alzheimer Disease; Trehalose; Clinical Trial; Autophagy

Outcome Measures

Primary Outcomes (2)

• Changes of Mini-Mental State Exam (MMSE)

  Global cognition will be assessed by MMSE test, which will be conducted at baseline and week 12.

  From baseline to 12 weeks

• Changes in Clinical Dementia Rating Scale (CDR)

  Clinical Dementia Rating Scale (CDR) has six different cognitive and behavioral domains such as memory, orientation, judgment and problem solving, community affairs, home and hobbies performance, and personal care, which will be conducted at baseline and week 12.

  From baseline to 12 weeks

Study Arms (2)

Trehalose

EXPERIMENTAL

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

Drug: Trehalose

Placebo

PLACEBO COMPARATOR

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

Drug: Trehalose

Interventions

Trehalose 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.

Also known as: Mycose

Placebo; Trehalose

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mashhad University of Medical Sciences: lead

Study Sites (1)

Ghaem Educational, Research and Treatment Center

Mashhad, Razavi Khorasan Province, 9919991766, Iran

RECRUITING

Related Publications (13)

• 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.

  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.

  PMID: 23305823 BACKGROUND

• 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.

  PMID: 25984581 BACKGROUND

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

  PMID: 14685252 BACKGROUND

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

  PMID: 9686307 BACKGROUND

• 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.

  PMID: 23477989 BACKGROUND

• 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.

  PMID: 20920466 BACKGROUND

• 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.

  PMID: 24236985 BACKGROUND

• 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.

  PMID: 15094052 BACKGROUND

• 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.

  PMID: 14730359 BACKGROUND

• 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.

  PMID: 28166771 BACKGROUND

• 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.

  PMID: 12065209 BACKGROUND

• 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.

  PMID: 21337544 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Trehalose

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Glucans; Polysaccharides; Carbohydrates; Disaccharides; Oligosaccharides; Sugars

Central Study Contacts

Amirhossien Sahebkar, PhD

CONTACT

+985138002299; SahebkarA@mums.ac.ir

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor at Mashhad University of Medical Sciences

Study Record Dates

• First Submitted: September 1, 2020
• First Posted: December 11, 2020
• Study Start: August 20, 2020
• Primary Completion: March 20, 2022
• Study Completion: August 20, 2022
• Last Updated: December 11, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

IR (1)