Brain Changes by Rivastigmine According to Butyrylcholinesterase Alleles
Primary Purpose
Alzheimer's Disease
Status
Unknown status
Phase
Not Applicable
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Rivastigmine
Sponsored by
About this trial
This is an interventional basic science trial for Alzheimer's Disease focused on measuring rivastigmine, butyrylcholinesterase, MRI, PET
Eligibility Criteria
Inclusion Criteria:
- Clinical diagnosis of Alzheimer's Disease (NINCD-ADRDA and MMSE between 10 ~26)
- Who didn't take Cholinesterase Inhibitor on liver within 3 months
Exclusion Criteria:
- 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
Sites / Locations
- Seoul Metropolitan Government Seoul National University Boramae Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Rivastigmine
Arm Description
Rivastigmine
Outcomes
Primary Outcome Measures
the mean changes of Standardized Uptake Values (SUVmean) in PET imaging
Unit: mg/100g/min
the mean changes of serum BuChE activity between BuChE wild type and K-variant type
unit of umil ACSCh/h/mg
Secondary Outcome Measures
the mean changes of cortical thickness in brain MRI
unit of mm
the cognitive changes in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog)
unit in points
the cognitive changes in Mini-Mental State Exam (MMSE)
unit in points
the daily function changes by Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
unit in points
the behavioural changes by Caregiver-Administered Neuropsychiatric Inventory (NPI)
unit in points
the disease severity changes by Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) between BuChE wild type and K-variant type
unit in points
Full Information
NCT ID
NCT02063269
First Posted
February 12, 2014
Last Updated
May 12, 2015
Sponsor
Seoul National University Hospital
Collaborators
Novartis Korea Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT02063269
Brief Title
Brain Changes by Rivastigmine According to Butyrylcholinesterase Alleles
Official Title
Differences of Functional Changes in Brain by Rivastigmine According to Butyrylcholinesterase Alleles in Alzheimer's Disease Patients(Rivastigmine, Imaging, and BuChE in AD: RIBA)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2015
Overall Recruitment Status
Unknown status
Study Start Date
February 2014 (undefined)
Primary Completion Date
June 2017 (Anticipated)
Study Completion Date
June 2017 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Seoul National University Hospital
Collaborators
Novartis Korea Ltd.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
Primary objective:
the mean changes of Standardized Uptake Values (SUVmean) in PET imaging
the mean changes of serum BuChE activity between BuChE wild type and K-variant type.
Secondary objectives:
the mean changes of cortical thickness in brain MRI
the cognitive changes in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog)
the cognitive changes in Mini-Mental State Exam (MMSE)
the daily function changes by Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
the behavioural changes by Caregiver-Administered Neuropsychiatric Inventory (NPI)
the disease severity changes by Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) between BuChE wild type and K-variant type.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
Keywords
rivastigmine, butyrylcholinesterase, MRI, PET
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
70 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Rivastigmine
Arm Type
Experimental
Arm Description
Rivastigmine
Intervention Type
Drug
Intervention Name(s)
Rivastigmine
Other Intervention Name(s)
Exelon
Intervention Description
9-18mg/rivastigmine for 52 weeks
Primary Outcome Measure Information:
Title
the mean changes of Standardized Uptake Values (SUVmean) in PET imaging
Description
Unit: mg/100g/min
Time Frame
screening and 52weeks (2 times)
Title
the mean changes of serum BuChE activity between BuChE wild type and K-variant type
Description
unit of umil ACSCh/h/mg
Time Frame
screening and 52weeks (2 times)
Secondary Outcome Measure Information:
Title
the mean changes of cortical thickness in brain MRI
Description
unit of mm
Time Frame
screening and 52weeks (2 times)
Title
the cognitive changes in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog)
Description
unit in points
Time Frame
screening, 26, and 52 weeks (3 times)
Title
the cognitive changes in Mini-Mental State Exam (MMSE)
Description
unit in points
Time Frame
screening, 26, and 52 weeks (3 times)
Title
the daily function changes by Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
Description
unit in points
Time Frame
screening, 26, and 52 weeks (3 times)
Title
the behavioural changes by Caregiver-Administered Neuropsychiatric Inventory (NPI)
Description
unit in points
Time Frame
screening, 26, and 52 weeks (3 times)
Title
the disease severity changes by Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) between BuChE wild type and K-variant type
Description
unit in points
Time Frame
screening, 26, and 52 weeks (3 times)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Clinical diagnosis of Alzheimer's Disease (NINCD-ADRDA and MMSE between 10 ~26)
Who didn't take Cholinesterase Inhibitor on liver within 3 months
Exclusion Criteria:
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
Facility Information:
Facility Name
Seoul Metropolitan Government Seoul National University Boramae Medical Center
City
Seoul
ZIP/Postal Code
156-707
Country
Korea, Republic of
12. IPD Sharing Statement
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Brain Changes by Rivastigmine According to Butyrylcholinesterase Alleles
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