Brain Changes by Rivastigmine According to Butyrylcholinesterase Alleles

NCT02063269 | Unknown DMC

• 1 other identifier: CENA713DKR15T
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Butyrylcholinesterase (BuChE) activity is increasing in Alzheimer Disease (AD) process (Lane et al., 2006). BuChE wild type has stronger butyrylcholine esterase activity than BuChE K variant allele and this strong activity can affect AD brain negatively by choline depletion. Rivastigmine has unique dual action - acetylcholine esterase inhibition and butyrylcholine esterase inhibition. Therefore, rivastigmine can lower serum butyrylcholine esterase activity and delay functional decrease of Fluorodeoxyglucose positron emission tomography (FDG PET) images in AD patients with BuChE wild type allele by strong BuChE inhibition. It suggests that rivastigmine can affect brain function differently by BuChE genotype in AD. Therefore, we will try to find the different changes of serum butyrylcholine esterase activity by ELISA and functional and structural changes of brain between BuChE wild type and K-variant type by FDG PET and MRI pre and post images after 12 month use of rivastigmine.

1. 1.Primary objective:
2. 2.the mean changes of Standardized Uptake Values (SUVmean) in PET imaging
3. 3.the mean changes of serum BuChE activity between BuChE wild type and K-variant type.
4. 4.Secondary objectives:
5. 5.the mean changes of cortical thickness in brain MRI
6. 6.the cognitive changes in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog)
7. 7.the cognitive changes in Mini-Mental State Exam (MMSE)
8. 8.the daily function changes by Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
9. 9.the behavioural changes by Caregiver-Administered Neuropsychiatric Inventory (NPI)
10. 10.the disease severity changes by Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) between BuChE wild type and K-variant type.

Conditions

Alzheimer's Disease

Keywords

rivastigmine, butyrylcholinesterase, MRI, PET

Outcome Measures

Primary Outcomes (2)

• the mean changes of Standardized Uptake Values (SUVmean) in PET imaging

  Unit: mg/100g/min

  screening and 52weeks (2 times)

• the mean changes of serum BuChE activity between BuChE wild type and K-variant type

  unit of umil ACSCh/h/mg

  screening and 52weeks (2 times)

Secondary Outcomes (6)

• the mean changes of cortical thickness in brain MRI

  screening and 52weeks (2 times)

• the cognitive changes in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog)

  screening, 26, and 52 weeks (3 times)

• the cognitive changes in Mini-Mental State Exam (MMSE)

  screening, 26, and 52 weeks (3 times)

• the daily function changes by Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)

  screening, 26, and 52 weeks (3 times)

• the behavioural changes by Caregiver-Administered Neuropsychiatric Inventory (NPI)

  screening, 26, and 52 weeks (3 times)

Study Arms (1)

Rivastigmine

EXPERIMENTAL

Rivastigmine

Drug: Rivastigmine

Interventions

Rivastigmine DRUG

9-18mg/rivastigmine for 52 weeks

Also known as: Exelon

Rivastigmine

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of Alzheimer's Disease (NINCD-ADRDA and MMSE between 10 \~26)
• Who didn't take Cholinesterase Inhibitor on liver within 3 months

You may not qualify if:

• diagnosed with diseases other than AD that affect brain atrophy according to Brain MRI
• Diagnosed with diseases other than AD which affect cognitive functions (i.g. Schizophrenia, Major Depression, Mental Retardation, encephalopathy, etc.)
• Didn't suspect of drug or alcohol addictions within last decade
• Unable to participate the study due to poor sight and hearing
• Who aren't suitable to participate according to the researchers' judgement

Sponsors & Collaborators

• Seoul National University Hospital: lead
• Novartis Korea Ltd.: collaborator

Study Sites (1)

Seoul Metropolitan Government Seoul National University Boramae Medical Center

Seoul, 156-707, South Korea

Location

Related Publications (15)

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  PMID: 11086186 BACKGROUND

• Blesa R, Bullock R, He Y, Bergman H, Gambina G, Meyer J, Rapatz G, Nagel J, Lane R. Effect of butyrylcholinesterase genotype on the response to rivastigmine or donepezil in younger patients with Alzheimer's disease. Pharmacogenet Genomics. 2006 Nov;16(11):771-4. doi: 10.1097/01.fpc.0000220573.05714.ac.

  PMID: 17047484 BACKGROUND

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  PMID: 63862 BACKGROUND

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  PMID: 21699607 BACKGROUND

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  PMID: 16083515 BACKGROUND

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  PMID: 10791868 BACKGROUND

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  PMID: 12668920 BACKGROUND

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  PMID: 12139368 BACKGROUND

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  PMID: 15867110 BACKGROUND

• Ki CS, Na DL, Kim JW, Kim HJ, Kim DK, Yoon BK. No association between the genes for butyrylcholinesterase K variant and apolipoprotein E4 in late-onset Alzheimer's disease. Am J Med Genet. 1999 Apr 16;88(2):113-5. doi: 10.1002/(sici)1096-8628(19990416)88:23.0.co;2-3.

  PMID: 10206226 BACKGROUND

• Kim KW, Jhoo JH, Lee JH, Lee KU, Lee DY, Youn JC, Youn JY, Woo JI. Neither the butyrylcholinesterase K variant nor transferrin C2 variant confers a risk for Alzheimer's disease in Koreans. J Neural Transm (Vienna). 2001;108(10):1159-66. doi: 10.1007/s007020170005.

  PMID: 11725818 BACKGROUND

• Jagust WJ, Bandy D, Chen K, Foster NL, Landau SM, Mathis CA, Price JC, Reiman EM, Skovronsky D, Koeppe RA; Alzheimer's Disease Neuroimaging Initiative. The Alzheimer's Disease Neuroimaging Initiative positron emission tomography core. Alzheimers Dement. 2010 May;6(3):221-9. doi: 10.1016/j.jalz.2010.03.003.

  PMID: 20451870 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease; Butyrylcholinesterase deficiency

Interventions

Rivastigmine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phenylcarbamates; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: February 12, 2014
• First Posted: February 14, 2014
• Study Start: February 1, 2014
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: May 14, 2015

Record last verified: 2015-05

Locations

KR (1)