The Clinical Response of Choline Acetyltransferase and Apolipoprotein Epsilon Gene Polymorphisms to Donepezil in Alzheimer's Disease

• Sponsor: Eisai Korea Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00381381
• Collaborator: (none)
• Enrollment: 199
• Locations: 15
• Arm: 1
• Actual Duration (Months): 31
• Patients Per Site: 13.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study attempts to differentiate the clinical responses of Choline Acetyltransferase and Apolipoprotein Epsilon gene polymorphism to donepezil in Alzheimer's Disease patients.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Drug: Donepezil	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 199 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-center Study for the Clinical Response of Choline Acetyltransferase and Apolipoprotein Epsilon Gene Polymorphisms to Donepezil in Alzheimer's Disease
• Actual Study Start Date: May 31, 2006
• Actual Primary Completion Date: Aug 31, 2008
• Actual Study Completion Date: Dec 31, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Donepezil; 2.5mg once daily for the first 7 days, 5mg once daily for the next 3 weeks, after then the dose can be increased 10mg once daily under the investigator's decision.; Other Names: Aricept

Outcome Measures

Primary Outcome Measures

1. CERAD-K (the Korean Version of the Consortium to Establish a Registry for Alzheimer's Disease) [26 weeks]

   CERAD-K includes: Verbal Fluency-number of kinds of animal patients listed per minute, ranges from 0, no maximum point fixed.Boston Naming Test is naming objects (0-15). Mini-Mental State Examination in the Korean version of CERAD Assessment Packet (0-30). Word List Memory (0-30). Construction Praxis is from 0-11. Word List Recall and Word List Recognition ranges from 0-10.Construction Recall (0-11).

2. CERAD-K [26 weeks]

   CERAD-K includes: Trail making test A and B is scored by the time spent to link randomly arranged numbers and alphabets in correct order. Except Trail making test A and B, higher score presents better condition.

Secondary Outcome Measures

1. Neuropsychiatry Inventory (NPI) [26 weeks]

   NPI score after treatment. NPI includes 12 sections which are Delusions, Hallucinations, Agitation, Depression, Anxiety, Euphoria, Apathy, Disinhibition, Irritability, Aberrant motor behavior, Night-time behaviors and Appetite and eating disorders. The score of each section ranges from 0 to 12, and higher score means higher severity and frequency of the neuropsychiatric disturbances.

2. GDS-K (Geriatric Depression Scale-Korean) Score After Treatment [26 weeks]

   GDS-K score after treatment. Geriatric Depression Scale is a basic screening measure for depression in older adults. It ranges from 0 to 30, and higher score represents more depressed.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

1. Age: 60 - 90 years old.

2. CDR: 0.5 - 2.0.

3. Patients who do not have severe depressive symptoms that affect cognition on depression scale of CERAD-K(C), GDS-K: 19 and below.

4. Modified Hachinski Ischemic Score (Rosen, et. al., 1979): 3 and below.

5. NINCDS-ADRDA criteria: Probable AD.

Exclusion criteria:

1. Patients who have delusions and other conscious dysfunction.

2. Patients who have neurologic diseases such as Parkinson's disease, stroke, tumor, normal pressure hydrocephalus, etc., on history and neurologic examination.

3. Patients who have history of infectious and inflammatory brain disease owing to virus, fungus and syphilis.

4. Patients with severe cerebrovascular pathology.

5. Patients who have present history of major psychological diseases such as depression and mania according to DSM-IV criteria.

6. Patients who have history of alcoholism or drug addiction.

7. Patients who have severe depressive symptoms that affect cognition on depression scale of CERAD-K.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Seoul National University Bundang Hospital	Bundang		Korea, Republic of
2	Hallym University Medical Center	Changwon		Korea, Republic of
3	Kangwon National University Hospital	Chuncheon		Korea, Republic of
4	Kunkuk University Chungju Hospital	Chungju		Korea, Republic of
5	Kyungpook National University Hospital	Daegu		Korea, Republic of
6	Chungnam National University Hospital	Daejeon		Korea, Republic of
7	Gyeonggi Province Geriatric Hospital	Gyeonggi		Korea, Republic of
8	Uijeongbu St. Mary's Hospital	Gyeonggi		Korea, Republic of
9	Jeju National University Hospital	Jeju		Korea, Republic of
10	Jeonju City Welfare Hospital	Jeonju		Korea, Republic of
11	Gyeongsang National University Hospital	Jinju		Korea, Republic of
12	Inje University Pusan Paik Hospital	Pusan		Korea, Republic of
13	Kunkuk University Hospital	Seoul		Korea, Republic of
14	Seoul National University Hospital	Seoul		Korea, Republic of
15	Seoul St. Mary's Hospital	Seoul		Korea, Republic of

Sponsors and Collaborators

• Eisai Korea Inc.

Investigators

• Study Director: Jihee Mun, Eisai Korea Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eisai Korea Inc.
• ClinicalTrials.gov Identifier: NCT00381381
• Other Study ID Numbers: EKI-6-004
• First Posted: Sep 27, 2006
• Last Update Posted: Jan 4, 2022
• Last Verified: Jul 1, 2010

• Keywords provided by Eisai Korea Inc.: Alzheimer's disease
• Additional relevant MeSH terms: Alzheimer Disease; Donepezil

Study Results

Participant Flow

Recruitment Details	This study was recruited at 15 centers in Korea during the period of June 2006 to August 2008.

Arm/Group Title	Donepezil
Arm/Group Description	Initial dose was 2.5 mg/day, and the maximum dose was 10 mg/day.
Period Title: Overall Study
STARTED	199
COMPLETED	135
NOT COMPLETED	64

Baseline Characteristics

Arm/Group Title	Donepezil
Arm/Group Description	Initial dose was 2.5 mg/day, and the maximum dose was 10 mg/day.
Overall Participants	199
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	74.6 (6.5)
Sex: Female, Male (Count of Participants)
Female	136 68.3%
Male	63 31.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	199 100%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	CERAD-K (the Korean Version of the Consortium to Establish a Registry for Alzheimer's Disease)
Description	CERAD-K includes: Verbal Fluency-number of kinds of animal patients listed per minute, ranges from 0, no maximum point fixed.Boston Naming Test is naming objects (0-15). Mini-Mental State Examination in the Korean version of CERAD Assessment Packet (0-30). Word List Memory (0-30). Construction Praxis is from 0-11. Word List Recall and Word List Recognition ranges from 0-10.Construction Recall (0-11).
Time Frame	26 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Donepezil
Arm/Group Description	Initial dose was 2.5 mg/day, and the maximum dose was 10 mg/day.
Measure Participants	135
Verbal Fluency	8.28 (3.71)
Boston Naming Test	7.31 (3.25)
MMSE-KC	17.86 (5.25)
Word List Memory	10.62 (6.20)
Construction Praxis	7.61 (2.71)
Word List Recall	1.98 (1.99)
Word List Recognition	4.64 (3.24)
Construction Recall	2.11 (2.71)

2. Secondary Outcome

Title	Neuropsychiatry Inventory (NPI)
Description	NPI score after treatment. NPI includes 12 sections which are Delusions, Hallucinations, Agitation, Depression, Anxiety, Euphoria, Apathy, Disinhibition, Irritability, Aberrant motor behavior, Night-time behaviors and Appetite and eating disorders. The score of each section ranges from 0 to 12, and higher score means higher severity and frequency of the neuropsychiatric disturbances.
Time Frame	26 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Donepezil
Arm/Group Description	Initial dose was 2.5 mg/day, and the maximum dose was 10 mg/day.
Measure Participants	135
Delusions	0.49 (1.85)
Hallucinations	0.12 (0.69)
Agitation	0.54 (1.56)
Depression	0.76 (1.82)
Anxiety	0.70 (2.10)
Euphoria	0.02 (0.19)
Apathy	1.44 (2.69)
Disinhibition	0.28 (1.19)
Irritability	0.67 (1.93)
Aberrant motor behavior	0.44 (1.71)
Night-time behaviors	0.40 (1.68)
Appetite and eating disorders	0.43 (1.46)

3. Secondary Outcome

Title	GDS-K (Geriatric Depression Scale-Korean) Score After Treatment
Description	GDS-K score after treatment. Geriatric Depression Scale is a basic screening measure for depression in older adults. It ranges from 0 to 30, and higher score represents more depressed.
Time Frame	26 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Donepezil
Arm/Group Description	Initial dose was 2.5 mg/day, and the maximum dose was 10 mg/day.
Measure Participants	135
Mean (Standard Deviation) [Units on Scale]	11.69 (6.42)

4. Primary Outcome

Title	CERAD-K
Description	CERAD-K includes: Trail making test A and B is scored by the time spent to link randomly arranged numbers and alphabets in correct order. Except Trail making test A and B, higher score presents better condition.
Time Frame	26 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Donepezil
Arm/Group Description	Initial dose was 2.5 mg/day, and the maximum dose was 10 mg/day.
Measure Participants	135
Trail making test A	206.64 (126.94)
Trail making test B	290.88 (30.20)

Adverse Events

Arm/Group Title	Donepezil
Arm/Group Description	Initial dose was 2.5 mg/day, and the maximum dose was 10 mg/day.
All Cause Mortality
	Donepezil
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Donepezil
	Affected / at Risk (%)	# Events
Total	4/199 (2%)
General disorders
General Weakness	1/199 (0.5%)	1
Malignancy Of Unknown Origin	1/199 (0.5%)	1
Musculoskeletal and connective tissue disorders
Ankle Fracture	1/199 (0.5%)	1
Psychiatric disorders
Anorexia	1/199 (0.5%)	1
Vascular disorders
Stroke	1/199 (0.5%)	1
Other (Not Including Serious) Adverse Events
	Donepezil
	Affected / at Risk (%)	# Events
Total	30/199 (15.1%)
Gastrointestinal disorders
Abdominal Discomfort	4/199 (2%)
Vomiting	2/199 (1%)
Nausea	5/199 (2.5%)
General disorders
Weakness	3/199 (1.5%)
Nervous system disorders
Dizziness	7/199 (3.5%)
Headache	5/199 (2.5%)
Psychiatric disorders
Anorexia	7/199 (3.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.