Trial Outcomes & Findings for Neural Correlates In Mild Alzheimer's Disease (NCT NCT00477659)

NCT ID: NCT00477659

Last Updated: 2021-11-10

Results Overview

All neuroimaging procedures were performed on a research-dedicated GE 3.0 Tesla whole-body Excite scanner with 8-channel phase-array head coil. Resting-state functional magnetic resonance imaging (fMRI) of the medial temporal lobe (MTL) was performed. The functional HCI was derived from the MTL network using a data driven approach corresponding voxel time courses from the fMR images were processed to extract low frequency fluctuations. Functional connectivity was quantified by calculating the cross-correlation of each voxel time course in the hippocampus to all voxel time courses of the whole brain and the mean of absolute cross-correlation coefficients between a hippocampus voxel to the whole-brain voxels. HCI was then calculated as the average of all hippocampus cross-correlation coefficients. Change from baseline (CFB) was calculated using the CBF-Perfusion Processing Method. A positive change from baseline for HCI indicates improved function.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 14 participants
• Primary outcome timeframe: Week 12
• Results posted on: 2021-11-10

Participant Flow

Participants took part in this study at one investigative site in the United States from 23 July 2007 to 15 August 2008.

Out of the 16 participants who were screened, 14 participants were enrolled into the study.

Participant milestones

Measure	Donepezil Hydrochloride Participants received donepezil hydrochloride 5 mg per day orally, once daily for 4 weeks, followed by 10 mg per day (two 5-mg tablets) for 8 weeks.
Overall Study STARTED	14
Overall Study COMPLETED	14
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Neural Correlates In Mild Alzheimer's Disease

Baseline characteristics by cohort

Measure	Donepezil n=14 Participants Participants received donepezil hydrochloride 5 mg per day orally, once daily for 4 weeks, followed by 10 mg per day (two 5-mg tablets) for 8 weeks.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	14 Participants n=5 Participants
Age, Continuous	77.6 years STANDARD_DEVIATION 6.6 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	14 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 12

Population: The ITT set included all participants who received at least one dose of study medication, had a baseline efficacy evaluation, and had at least one post-baseline efficacy evaluation.

All neuroimaging procedures were performed on a research-dedicated GE 3.0 Tesla whole-body Excite scanner with 8-channel phase-array head coil. Resting-state functional magnetic resonance imaging (fMRI) of the medial temporal lobe (MTL) was performed. The functional HCI was derived from the MTL network using a data driven approach corresponding voxel time courses from the fMR images were processed to extract low frequency fluctuations. Functional connectivity was quantified by calculating the cross-correlation of each voxel time course in the hippocampus to all voxel time courses of the whole brain and the mean of absolute cross-correlation coefficients between a hippocampus voxel to the whole-brain voxels. HCI was then calculated as the average of all hippocampus cross-correlation coefficients. Change from baseline (CFB) was calculated using the CBF-Perfusion Processing Method. A positive change from baseline for HCI indicates improved function.

Outcome measures

Measure	Donepezil Hydrochloride n=14 Participants Participants received donepezil hydrochloride 5 mg per day orally, once daily for 4 weeks, followed by 10 mg per day (two 5-mg tablets) for 8 weeks.
Percent Change From Baseline to Week 12 Based on Hippocampus Connectivity Index (HCI)	7.47 percent change Standard Deviation 17.23

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The ITT set included all participants who received at least one dose of study medication, had a baseline efficacy evaluation, and had at least one post-baseline efficacy evaluation.

The ADAS-cog is a 13-item performance-based test that examines selected aspects of cognition including memory, orientation, attention, reasoning, language, and praxis. Total score ranges from 0 to 70 with higher scores indicating greater cognitive impairment. A decrease from baseline indicates improved cognitive function. The ADAS-cog was administered by a trained individual unaware of adverse events reported during this trial.

Outcome measures

Measure	Donepezil Hydrochloride n=14 Participants Participants received donepezil hydrochloride 5 mg per day orally, once daily for 4 weeks, followed by 10 mg per day (two 5-mg tablets) for 8 weeks.
Change From Baseline at Week 12 in Alzheimer's Disease Assessment Scale - Cognitive Scale (ADAS)-Cog Score Baseline	12.0 score on a scale Standard Deviation 4.85
Change From Baseline at Week 12 in Alzheimer's Disease Assessment Scale - Cognitive Scale (ADAS)-Cog Score Change at Week 12	-1.6 score on a scale Standard Deviation 2.81

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The ITT set included all participants who received at least one dose of study medication, had a baseline efficacy evaluation, and had at least one post-baseline efficacy evaluation.

MMSE was a 11-item scale to measure cognitive status where a higher score indicated better cognitive state. The score ranged from 0 to 30, with a higher score indicating better function. A positive change score indicated improvement from baseline. The mean change was analyzed by Wilcoxon's signed rank test.

Outcome measures

Measure	Donepezil Hydrochloride n=14 Participants Participants received donepezil hydrochloride 5 mg per day orally, once daily for 4 weeks, followed by 10 mg per day (two 5-mg tablets) for 8 weeks.
Change From Baseline at Week 12 in Mini-Mental State Examination (MMSE) Score Baseline	26.1 score on a scale Standard Deviation 1.33
Change From Baseline at Week 12 in Mini-Mental State Examination (MMSE) Score Change at Week 12	0.1 score on a scale Standard Deviation 2.70

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The ITT set included all participants who received at least one dose of study medication, had a baseline efficacy evaluation, and had at least one post-baseline efficacy evaluation.

IADL Scale measures 7 areas of more complex activities required for optimal independent functioning, as reported by the caregiver. The scoring indicates whether the participant was completely independent (3), requires assistance (2), or is dependent (1) for the performance of each activity. A summary score ranges from 7 (high function, independent) to 21 (low function, dependent). The mean change was analyzed by Wilcoxon's signed rank test. A decrease from Baseline to Week 12 indicates improved function.

Outcome measures

Measure	Donepezil Hydrochloride n=14 Participants Participants received donepezil hydrochloride 5 mg per day orally, once daily for 4 weeks, followed by 10 mg per day (two 5-mg tablets) for 8 weeks.
Change From Baseline at Week 12 in the Instrumental Activities of Daily Living (IADL) Assessment Score Baseline	13.1 score on a scale Standard Deviation 3.71
Change From Baseline at Week 12 in the Instrumental Activities of Daily Living (IADL) Assessment Score Change at Week 12	-0.3 score on a scale Standard Deviation 2.70

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The ITT set included all participants who received at least one dose of study medication, had a baseline efficacy evaluation, and had at least one post-baseline efficacy evaluation.

NPI was a 12-item caregiver-based assessment of behavioral disturbances commonly occurring in participants with AD. 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. The mean change was analyzed by Wilcoxon's signed rank test.

Outcome measures

Measure	Donepezil Hydrochloride n=14 Participants Participants received donepezil hydrochloride 5 mg per day orally, once daily for 4 weeks, followed by 10 mg per day (two 5-mg tablets) for 8 weeks.
Change From Baseline at Week 12 in the Neuropsychiatric Inventory (NPI) Score Baseline	9.2 score on a scale Standard Deviation 10.00
Change From Baseline at Week 12 in the Neuropsychiatric Inventory (NPI) Score Change at Week 12	-3.4 score on a scale Standard Deviation 11.25

Adverse Events

Donepezil Hydrochloride

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Donepezil Hydrochloride n=14 participants at risk Participants received donepezil hydrochloride 5 mg per day orally, once daily for 4 weeks, followed by 10 mg per day (two 5-mg tablets) for 8 weeks.
Metabolism and nutrition disorders Decreased appetite	7.1% 1/14 • All adverse events were collected from first dose of study drug (Baseline) up to 30 days after last dose of study drug (approximately up to 12 weeks) Safety analysis set included all participants who received at least one dose of study medication.
Metabolism and nutrition disorders Weight loss	7.1% 1/14 • All adverse events were collected from first dose of study drug (Baseline) up to 30 days after last dose of study drug (approximately up to 12 weeks) Safety analysis set included all participants who received at least one dose of study medication.
Ear and labyrinth disorders Ear pain	7.1% 1/14 • All adverse events were collected from first dose of study drug (Baseline) up to 30 days after last dose of study drug (approximately up to 12 weeks) Safety analysis set included all participants who received at least one dose of study medication.
Eye disorders Eye pain	7.1% 1/14 • All adverse events were collected from first dose of study drug (Baseline) up to 30 days after last dose of study drug (approximately up to 12 weeks) Safety analysis set included all participants who received at least one dose of study medication.
Eye disorders Vision blurred	7.1% 1/14 • All adverse events were collected from first dose of study drug (Baseline) up to 30 days after last dose of study drug (approximately up to 12 weeks) Safety analysis set included all participants who received at least one dose of study medication.
Gastrointestinal disorders Diarrhea	14.3% 2/14 • All adverse events were collected from first dose of study drug (Baseline) up to 30 days after last dose of study drug (approximately up to 12 weeks) Safety analysis set included all participants who received at least one dose of study medication.
Gastrointestinal disorders Feces discolored	7.1% 1/14 • All adverse events were collected from first dose of study drug (Baseline) up to 30 days after last dose of study drug (approximately up to 12 weeks) Safety analysis set included all participants who received at least one dose of study medication.
Gastrointestinal disorders Flatulence	7.1% 1/14 • All adverse events were collected from first dose of study drug (Baseline) up to 30 days after last dose of study drug (approximately up to 12 weeks) Safety analysis set included all participants who received at least one dose of study medication.
Gastrointestinal disorders Stomach discomfort	7.1% 1/14 • All adverse events were collected from first dose of study drug (Baseline) up to 30 days after last dose of study drug (approximately up to 12 weeks) Safety analysis set included all participants who received at least one dose of study medication.
General disorders Asthenia	7.1% 1/14 • All adverse events were collected from first dose of study drug (Baseline) up to 30 days after last dose of study drug (approximately up to 12 weeks) Safety analysis set included all participants who received at least one dose of study medication.
Injury, poisoning and procedural complications Contusion	7.1% 1/14 • All adverse events were collected from first dose of study drug (Baseline) up to 30 days after last dose of study drug (approximately up to 12 weeks) Safety analysis set included all participants who received at least one dose of study medication.
Metabolism and nutrition disorders Hypercholesterolemia	7.1% 1/14 • All adverse events were collected from first dose of study drug (Baseline) up to 30 days after last dose of study drug (approximately up to 12 weeks) Safety analysis set included all participants who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Muscle spasms	7.1% 1/14 • All adverse events were collected from first dose of study drug (Baseline) up to 30 days after last dose of study drug (approximately up to 12 weeks) Safety analysis set included all participants who received at least one dose of study medication.
Nervous system disorders Headache	7.1% 1/14 • All adverse events were collected from first dose of study drug (Baseline) up to 30 days after last dose of study drug (approximately up to 12 weeks) Safety analysis set included all participants who received at least one dose of study medication.
Psychiatric disorders Abnormal dreams	7.1% 1/14 • All adverse events were collected from first dose of study drug (Baseline) up to 30 days after last dose of study drug (approximately up to 12 weeks) Safety analysis set included all participants who received at least one dose of study medication.
Psychiatric disorders Nervousness	7.1% 1/14 • All adverse events were collected from first dose of study drug (Baseline) up to 30 days after last dose of study drug (approximately up to 12 weeks) Safety analysis set included all participants who received at least one dose of study medication.
Psychiatric disorders Nightmare	7.1% 1/14 • All adverse events were collected from first dose of study drug (Baseline) up to 30 days after last dose of study drug (approximately up to 12 weeks) Safety analysis set included all participants who received at least one dose of study medication.
Psychiatric disorders Obsessive thoughts	7.1% 1/14 • All adverse events were collected from first dose of study drug (Baseline) up to 30 days after last dose of study drug (approximately up to 12 weeks) Safety analysis set included all participants who received at least one dose of study medication.
Psychiatric disorders Sleep disorder	7.1% 1/14 • All adverse events were collected from first dose of study drug (Baseline) up to 30 days after last dose of study drug (approximately up to 12 weeks) Safety analysis set included all participants who received at least one dose of study medication.
Renal and urinary disorders Micturition urgency	7.1% 1/14 • All adverse events were collected from first dose of study drug (Baseline) up to 30 days after last dose of study drug (approximately up to 12 weeks) Safety analysis set included all participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	7.1% 1/14 • All adverse events were collected from first dose of study drug (Baseline) up to 30 days after last dose of study drug (approximately up to 12 weeks) Safety analysis set included all participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Rhinorrhea	14.3% 2/14 • All adverse events were collected from first dose of study drug (Baseline) up to 30 days after last dose of study drug (approximately up to 12 weeks) Safety analysis set included all participants who received at least one dose of study medication.

Additional Information

Eisai Medical Services

Eisai, Inc.

Phone: 1-888-422-4743

Email: esi_medinfo@eisai.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place