The Efficacy of Galantamine Treatment on Attention in Patients With Alzheimer's Disease

• Sponsor: Janssen Korea, Ltd., Korea (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01054976
• Collaborator: (none)
• Enrollment: 99
• Arm: 1
• Duration (Months): 28.1

Study Details

Study Description

Brief Summary

This study will examine whether the administration of galantamine is effective for improvement of attention and more effective for patients with serious disturbance of attention by administering galantamine to patients with Alzheimer's dementia and performing an attention test on baseline, week 4 and 12.

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

Detailed Description

This is an open label (all people know the identity of the intervention), multi-center, prospective study investigating the effect of galantamine on the attention of Alzheimer's dementia patients. The objectives of this study include the evaluation of the relationship between change in attention after 4 weeks of galantamine administration and to investigate the effect of study drug after 12 weeks administration (the difference in the improvement of attention after the administration of galantamine). The secondary objective of this study is to clarify the causal relationship between improvement of attention and activities of daily living (ADL). The design of this study is prospective, open-label, multi-center study. Study populations are probable Alzheimer's dementia patients diagnosed by NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's disease and Related Disorders Association), DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) criteria. The efficacy of study drug will be assessed by evaluating cognitive function, attention and behavioral symptoms before and after the treatment using the following assessment tools: ADAS-K-cog11 (Alzheimer's Disease Assessment Scale - cognitive subscale), computerized attention test and activities of daily living. Safety evaluations include adverse event monitoring and clinical lab tests. The patient is administered oral galantamine 8 mg/day for the first 4 weeks and then 16 mg/day. The dose of galantamine is increased up to 24 mg if tolerated.

Study Design

• Study Type: Interventional
• Actual Enrollment: 99 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Efficacy of Galantamine Treatment on Attention in Patients With Alzheimer's Disease
• Study Start Date: Oct 1, 2006
• Actual Primary Completion Date: Feb 1, 2009
• Actual Study Completion Date: Feb 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Galantamine	Drug: Galantamine; Orally administered Galantamine 8 mg/day for the first 4 weeks. Thereafter the dose will be increased to 16 mg/day. If tolerated, the dose of galantamine can be increased up to 24 mg/day.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Simple Reaction Time [Baseline, Week 12]

   The Simple Reaction Time is a computerized attention test that evaluates the patient's reaction time when the color of the computer screen changes from black to white by performing a total of 70 times for six minutes.

2. Change From Baseline in Choice Reaction Time [Baseline, Week 12]

   The Choice Reaction Time is a computerized attention test that evaluates the reaction time and the number of errors by showing patients one card on the computer screen and making them find the same one among similar four cards. The test is performed a total of 12 times.

Secondary Outcome Measures

1. Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) [Baseline, Week 12]

   The Alzheimer's disease Assessment Scale-Cognitive subscale (ADAS-Cog) is an instrument used to assess cognitive dysfunction in individuals with Alzheimer disease and other dementias. It consists of 11 items, with scores ranging from 1 to 70. Maximum score is 70. Higher scores indicate worsening.

2. Change From Baseline in Korean Version of Disability Assessment for Demential Scale (DAD-K) [Baseline, Week 12]

   DAD-K is the Korean version of the Assessment for Dementia Scale, a tool developed to evaluate the Alzheimer patients' function including both basic and instrumental Activities of Daily Livings (ADL). It evaluates one function from various perspectives including behavior initiation, plan and preparation, and valid performance. It consists of 10 questions, each can score either 0 (no) or 1 (yes), if not applicable, patient will check on "not applicable (x)" which will not count in the calculation. Scores range from 0 to 100. Higher score represents better function

3. Change From Baseline in Seoul-Instrumental Activities of Daily Livings (S-IADL) [Baseline, Week 12]

   The Seoul-Instrumental Activities of Daily Living (S-IADL) assesses patients' abilities to perform instrumental and social activities of daily living. These include the ability to prepare a balanced meal, remember appointments, keep financial records, remember to take medication, and so on. It is composed of 15 items, with scores ranging from 0 to 45. Lower scores indicate better functioning.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Alzheimer's disease according to the criteria of DSM-IV, NINCDS-ADRDA

• K-MMSE (Korean - Mini Mental State Exam) is 10 to 24

• Reliable Guardian available to the patients

• Patient or guardian provided written informed consent before entering into the clinical trial

Exclusion Criteria:

• Acetylcholine esterase inhibitors used to treat dementia taken within 30 days of the beginning in this clinical trial

• Neurodegenerative diseases (eg Parkinson's disease, Pick's disease, Huntington's disease, Down syndrome)

• Dementia related to head trauma and dementia related to brain damage due to cerebral hypoxia (hypoxic brain damage after cardiopulmonary resuscitation, hypoxic brain damage after surgery, hypoxic brain damage due to addiction, hypoxic brain damage due to shock)

• brain tumor, nerve syphilis, meningitis, encephalitis

• epilepsy

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Janssen Korea, Ltd., Korea

Investigators

• Study Director: Janssen Korea, Ltd. Clinical Trial, Janssen Korea, Ltd.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen Korea, Ltd., Korea
• ClinicalTrials.gov Identifier: NCT01054976
• Other Study ID Numbers: CR015850; GAL-KOR-21; GALALZ4039
• First Posted: Jan 22, 2010
• Last Update Posted: Dec 24, 2012
• Last Verified: Nov 1, 2012

• Keywords provided by Janssen Korea, Ltd., Korea: Alzheimer's disease; Galantamine; Dementia
• Additional relevant MeSH terms: Alzheimer Disease; Galantamine

Study Results

Participant Flow

Recruitment Details	Of the total of 99 enrolled patients, only 92 were screened.

Arm/Group Title	Galantamine
Arm/Group Description	8 mg/day for 4 weeks; 16 mg/day thereafter
Period Title: Overall Study
STARTED	92
COMPLETED	57
NOT COMPLETED	35

Baseline Characteristics

Arm/Group Title	Galantamine
Arm/Group Description	8 mg/day for 4 weeks; 16 mg/day thereafter
Overall Participants	92
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	73.24 (7.969)
Sex: Female, Male (Count of Participants)
Female	70 76.1%
Male	22 23.9%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Simple Reaction Time
Description	The Simple Reaction Time is a computerized attention test that evaluates the patient's reaction time when the color of the computer screen changes from black to white by performing a total of 70 times for six minutes.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Per-protocol (PP) analysis set.

Arm/Group Title	Galantamine
Arm/Group Description	8 mg/day for 4 weeks; 16 mg/day thereafter
Measure Participants	92
Week 4 (n=83)	-30.92 (1277.0)
Week 12 (n=73)	180.83 (519.18)

2. Primary Outcome

Title	Change From Baseline in Choice Reaction Time
Description	The Choice Reaction Time is a computerized attention test that evaluates the reaction time and the number of errors by showing patients one card on the computer screen and making them find the same one among similar four cards. The test is performed a total of 12 times.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Per-protocol (PP) analysis set.

Arm/Group Title	Galantamine
Arm/Group Description	8 mg/day for 4 weeks; 16 mg/day thereafter
Measure Participants	92
Week 4 (n=80)	429.54 (3388.0)
Week 12 (n=73)	1331 (3627.0)

3. Secondary Outcome

Title	Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog)
Description	The Alzheimer's disease Assessment Scale-Cognitive subscale (ADAS-Cog) is an instrument used to assess cognitive dysfunction in individuals with Alzheimer disease and other dementias. It consists of 11 items, with scores ranging from 1 to 70. Maximum score is 70. Higher scores indicate worsening.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Intention-to-Treat analysis set.

Arm/Group Title	Galantamine
Arm/Group Description	8 mg/day for 4 weeks; 16 mg/day thereafter
Measure Participants	73
Mean (Standard Deviation) [scores on a scale]	1.31 (5.67)

4. Secondary Outcome

Title	Change From Baseline in Korean Version of Disability Assessment for Demential Scale (DAD-K)
Description	DAD-K is the Korean version of the Assessment for Dementia Scale, a tool developed to evaluate the Alzheimer patients' function including both basic and instrumental Activities of Daily Livings (ADL). It evaluates one function from various perspectives including behavior initiation, plan and preparation, and valid performance. It consists of 10 questions, each can score either 0 (no) or 1 (yes), if not applicable, patient will check on "not applicable (x)" which will not count in the calculation. Scores range from 0 to 100. Higher score represents better function
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Intention-to-Treat analysis set.

Arm/Group Title	Galantamine
Arm/Group Description	8 mg/day for 4 weeks; 16 mg/day thereafter
Measure Participants	73
Mean (Standard Deviation) [scores on a scale]	-1.41 (10.53)

5. Secondary Outcome

Title	Change From Baseline in Seoul-Instrumental Activities of Daily Livings (S-IADL)
Description	The Seoul-Instrumental Activities of Daily Living (S-IADL) assesses patients' abilities to perform instrumental and social activities of daily living. These include the ability to prepare a balanced meal, remember appointments, keep financial records, remember to take medication, and so on. It is composed of 15 items, with scores ranging from 0 to 45. Lower scores indicate better functioning.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Intention-to-Treat analysis set.

Arm/Group Title	Galantamine
Arm/Group Description	8 mg/day for 4 weeks; 16 mg/day thereafter
Measure Participants	73
Mean (Standard Deviation) [scores on a scale]	1.22 (6.88)

Adverse Events

Time Frame	12 weeks
Arm/Group Title	Galantamine
Arm/Group Description	8 mg/day for 4 weeks; 16 mg/day thereafter
All Cause Mortality
	Galantamine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Galantamine
	Affected / at Risk (%)	# Events
Total	8/92 (8.7%)
Gastrointestinal disorders
Nausea	1/92 (1.1%)
General disorders
Headache	1/92 (1.1%)
Injury, poisoning and procedural complications
Fall	2/92 (2.2%)
Fracture	2/92 (2.2%)
Metabolism and nutrition disorders
Hyperglycemia	1/92 (1.1%)
Musculoskeletal and connective tissue disorders
Asthenia	1/92 (1.1%)
Nervous system disorders
Brain stem infarction	1/92 (1.1%)
Neuromyopathy	1/92 (1.1%)
Psychiatric disorders
Delirium	1/92 (1.1%)
Other (Not Including Serious) Adverse Events
	Galantamine
	Affected / at Risk (%)	# Events
Total	41/92 (44.6%)
Cardiac disorders
Chest discomfort	2/92 (2.2%)
Ear and labyrinth disorders
Tinnitus	1/92 (1.1%)
Hearing loss	1/92 (1.1%)
Gastrointestinal disorders
Nausea	15/92 (16.3%)
Vomiting	5/92 (5.4%)
Diarrhea	4/92 (4.3%)
Dyspepsia	2/92 (2.2%)
Abdominal discomfort	2/92 (2.2%)
Belching	1/92 (1.1%)
Constipation	1/92 (1.1%)
Intermittent indigestion	1/92 (1.1%)
General disorders
Headache	5/92 (5.4%)
Insomnia	2/92 (2.2%)
Cold	2/92 (2.2%)
Lethargy	2/92 (2.2%)
Fall	1/92 (1.1%)
Fatigue	1/92 (1.1%)
Sleep disorder	1/92 (1.1%)
Sun stroke	1/92 (1.1%)
Sweating	1/92 (1.1%)
Somnolence	1/92 (1.1%)
Metabolism and nutrition disorders
Weight loss	2/92 (2.2%)
Poor appetite	2/92 (2.2%)
Musculoskeletal and connective tissue disorders
Asthenia	2/92 (2.2%)
Arthralgia	1/92 (1.1%)
Rigor	1/92 (1.1%)
Knee pain	1/92 (1.1%)
Nervous system disorders
Dizziness/vertigo	7/92 (7.6%)
Anorexia	6/92 (6.5%)
Tonic pain	1/92 (1.1%)
Tremor	1/92 (1.1%)
Psychiatric disorders
Depression	1/92 (1.1%)
Dementia	1/92 (1.1%)
Confusion	1/92 (1.1%)

Limitations/Caveats

A relatively low number of patients finished the study, which may have had an impact on the statistical power of data analysis. Difficulties in performing computer-based tests for elderly patients may have hampered detection of changes in attention.

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release (time limit not indicated).