Trial Outcomes & Findings for Effects of Donepezil HCL on Task-Activated fMRI Brain Activation in Healthy Older Adults at Genetic Risk for Alzheimer's Disease (NCT NCT02087865)
NCT ID: NCT02087865
Last Updated: 2023-08-30
Results Overview
Changes from baseline to 24 weeks follow-up fMRI - Left posterior cingulate BOLD signal at 24 weeks, adjusting for baseline left posterior cingulate BOLD signal.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
89 participants
Primary outcome timeframe
Baseline and 24 Weeks
Results posted on
2023-08-30
Participant Flow
Participant milestones
| Measure |
Donepezil HCL
Participants will receive 5mg of donepezil HCL for 4 weeks and then 10mg of donepezil HCL for 20 weeks.
donepezil HCL
|
Placebo
Participants will receive placebo for 24 weeks.
Placebo
|
Control Group
Participants without a family history of AD will undergo the study evaluations but will not receive any study drug
|
|---|---|---|---|
|
Overall Study
STARTED
|
28
|
29
|
32
|
|
Overall Study
COMPLETED
|
22
|
26
|
29
|
|
Overall Study
NOT COMPLETED
|
6
|
3
|
3
|
Reasons for withdrawal
| Measure |
Donepezil HCL
Participants will receive 5mg of donepezil HCL for 4 weeks and then 10mg of donepezil HCL for 20 weeks.
donepezil HCL
|
Placebo
Participants will receive placebo for 24 weeks.
Placebo
|
Control Group
Participants without a family history of AD will undergo the study evaluations but will not receive any study drug
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
6
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
1
|
|
Overall Study
Drug Non-compliance
|
0
|
2
|
0
|
|
Overall Study
Not analyzed due to anatomical abnormalities
|
0
|
1
|
1
|
Baseline Characteristics
Effects of Donepezil HCL on Task-Activated fMRI Brain Activation in Healthy Older Adults at Genetic Risk for Alzheimer's Disease
Baseline characteristics by cohort
| Measure |
Donepezil HCL
n=22 Participants
Participants will receive 5mg of donepezil HCL for 4 weeks and then 10mg of donepezil HCL for 20 weeks.
donepezil HCL
|
Placebo
n=26 Participants
Participants will receive placebo for 24 weeks.
Placebo
|
Control Group
n=29 Participants
Participants without a family history of AD will undergo the study evaluations but will not receive any study drug
|
Total
n=77 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
26 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
16 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
51 Participants
n=4 Participants
|
|
Age, Continuous
|
66.4 years
STANDARD_DEVIATION 4.1 • n=5 Participants
|
66.1 years
STANDARD_DEVIATION 3.8 • n=7 Participants
|
67.7 years
STANDARD_DEVIATION 4.7 • n=5 Participants
|
66.8 years
STANDARD_DEVIATION 4.2 • n=4 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
48 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
29 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
22 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
76 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
21 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
69 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
22 participants
n=5 Participants
|
26 participants
n=7 Participants
|
29 participants
n=5 Participants
|
77 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline and 24 WeeksPopulation: Please note that the fMRI result of one subject was collected but could not be processed due to data quality issues. Hence, only 21 subjects in Donepezil HCL arm were analyzed.
Changes from baseline to 24 weeks follow-up fMRI - Left posterior cingulate BOLD signal at 24 weeks, adjusting for baseline left posterior cingulate BOLD signal.
Outcome measures
| Measure |
Donepezil HCL
n=21 Participants
Participants will receive 5mg of donepezil HCL for 4 weeks and then 10mg of donepezil HCL for 20 weeks.
donepezil HCL
|
Placebo
n=26 Participants
Participants will receive placebo for 24 weeks.
Placebo
|
Control Group
n=29 Participants
Participants without a family history of AD will undergo the study evaluations but will not receive any study drug
|
|---|---|---|---|
|
Change in BOLD Response From Baseline to 24 Weeks During Functional Magnetic Resonance Imaging - Left Posterior Cingulate BOLD Signal at 24 Weeks, Adjusting for Baseline Left Posterior Cingulate BOLD
|
44.68 100 * % Signal Change
Standard Deviation 33.86
|
50.61 100 * % Signal Change
Standard Deviation 23.46
|
45.57 100 * % Signal Change
Standard Deviation 25.24
|
PRIMARY outcome
Timeframe: Baseline and 24 WeeksPopulation: Please note that the fMRI result of one subject was collected but could not be processed due to data quality issues. Hence, only 21 subjects in Donepezil HCL arm were analyzed.
Left hippocampus BOLD signal at 24 weeks, adjusting for baseline left hippocampus BOLD signal.
Outcome measures
| Measure |
Donepezil HCL
n=21 Participants
Participants will receive 5mg of donepezil HCL for 4 weeks and then 10mg of donepezil HCL for 20 weeks.
donepezil HCL
|
Placebo
n=26 Participants
Participants will receive placebo for 24 weeks.
Placebo
|
Control Group
n=29 Participants
Participants without a family history of AD will undergo the study evaluations but will not receive any study drug
|
|---|---|---|---|
|
Left Hippocampus BOLD Signal at 24 Weeks, Adjusted for Baseline Left Hippocampus BOLD Signal
|
19.91 100 * % Signal Change
Standard Deviation 8.69
|
32.31 100 * % Signal Change
Standard Deviation 16.62
|
19.38 100 * % Signal Change
Standard Deviation 14.02
|
PRIMARY outcome
Timeframe: Baseline and 24 WeeksPopulation: Please note that the fMRI result of one subject was collected but could not be processed due to data quality issues. Hence, only 21 subjects in Donepezil HCL arm were analyzed.
Right hippocampus BOLD signal at 24 weeks, adjusting for baseline left hippocampus BOLD signal.
Outcome measures
| Measure |
Donepezil HCL
n=21 Participants
Participants will receive 5mg of donepezil HCL for 4 weeks and then 10mg of donepezil HCL for 20 weeks.
donepezil HCL
|
Placebo
n=26 Participants
Participants will receive placebo for 24 weeks.
Placebo
|
Control Group
n=29 Participants
Participants without a family history of AD will undergo the study evaluations but will not receive any study drug
|
|---|---|---|---|
|
Right Hippocampus BOLD Signal at 24 Weeks, Adjusted for Baseline Left Hippocampus BOLD Signal
|
24.9 100 * % Signal Change
Standard Deviation 18.72
|
32.78 100 * % Signal Change
Standard Deviation 20.57
|
26.73 100 * % Signal Change
Standard Deviation 18.09
|
SECONDARY outcome
Timeframe: Baseline and 24 WeeksRey Auditory Verbal Learning Test (RAVLT) (Sum of Trials 1-5) , adjusting for baseline RAVLT (Sum of Trials 1-5) score. The RAVLT total score has a minimum of 0 and a maximum of 75 correct items (15 per trial x 5 trials). A higher score means better outcomes.
Outcome measures
| Measure |
Donepezil HCL
n=22 Participants
Participants will receive 5mg of donepezil HCL for 4 weeks and then 10mg of donepezil HCL for 20 weeks.
donepezil HCL
|
Placebo
n=26 Participants
Participants will receive placebo for 24 weeks.
Placebo
|
Control Group
n=29 Participants
Participants without a family history of AD will undergo the study evaluations but will not receive any study drug
|
|---|---|---|---|
|
Neuropsychological Testing Scores - Rey Auditory Verbal Learning Test (RAVLT) Sum of Trials (1-5) at 24 Weeks, Adjusted for Baseline RAVLT Score
|
52.86 Total number of correct items
Standard Deviation 7.76
|
53.58 Total number of correct items
Standard Deviation 9.71
|
51.41 Total number of correct items
Standard Deviation 7.40
|
SECONDARY outcome
Timeframe: Baseline and 24 WeeksLeft hippocampus volume (MRI) at 24 weeks, adjusting for baseline left hippocampus volume
Outcome measures
| Measure |
Donepezil HCL
n=22 Participants
Participants will receive 5mg of donepezil HCL for 4 weeks and then 10mg of donepezil HCL for 20 weeks.
donepezil HCL
|
Placebo
n=26 Participants
Participants will receive placebo for 24 weeks.
Placebo
|
Control Group
n=29 Participants
Participants without a family history of AD will undergo the study evaluations but will not receive any study drug
|
|---|---|---|---|
|
Left Hippocampus Volume (MRI) at 24 Weeks, Adjusted for Baseline Left Hippocampus Volume
|
3309.51 mm^3
Standard Deviation 300.08
|
3289.36 mm^3
Standard Deviation 260.1
|
3296.68 mm^3
Standard Deviation 312.89
|
SECONDARY outcome
Timeframe: Baseline and 24 WeeksRight hippocampus volume (MRI) at 24 weeks, adjusting for baseline right hippocampus volume
Outcome measures
| Measure |
Donepezil HCL
n=22 Participants
Participants will receive 5mg of donepezil HCL for 4 weeks and then 10mg of donepezil HCL for 20 weeks.
donepezil HCL
|
Placebo
n=26 Participants
Participants will receive placebo for 24 weeks.
Placebo
|
Control Group
n=29 Participants
Participants without a family history of AD will undergo the study evaluations but will not receive any study drug
|
|---|---|---|---|
|
Right Hippocampus Volume (MRI) at 24 Weeks, Adjusted for Baseline Right Hippocampus Volume
|
1810.88 mm^3
Standard Deviation 231.08
|
1756.92 mm^3
Standard Deviation 183.39
|
3363.62 mm^3
Standard Deviation 214.59
|
SECONDARY outcome
Timeframe: Baseline and 24 WeeksBrief Visuospatial Memory Test (BVMT) learning scores at 24 weeks, adjusted for baseline BVMT learning scores. The BVMT-R total scare has a minimum of 0 and a maximum of 36 correct items (12 per trial x 3 trials). A higher score means better outcomes.
Outcome measures
| Measure |
Donepezil HCL
n=22 Participants
Participants will receive 5mg of donepezil HCL for 4 weeks and then 10mg of donepezil HCL for 20 weeks.
donepezil HCL
|
Placebo
n=26 Participants
Participants will receive placebo for 24 weeks.
Placebo
|
Control Group
n=29 Participants
Participants without a family history of AD will undergo the study evaluations but will not receive any study drug
|
|---|---|---|---|
|
Brief Visuospatial Memory Test (BVMT) Learning Scores at 24 Weeks, Adjusted for Baseline BVMT Learning Scores
|
21.41 Total number of correct items
Standard Deviation 6.17
|
23.58 Total number of correct items
Standard Deviation 5.84
|
23.28 Total number of correct items
Standard Deviation 5.07
|
SECONDARY outcome
Timeframe: Baseline and 24 WeeksPopulation: Please note only those participants who had complete PST data were included in the analysis, which are 12 participants in Donepezil HCL group, 15 participants in Placebo group, and 22 participants in Control group.
Processing speed test (PST) at 24 weeks, adjusting for baseline PST scores. The PST has a minimum of 0 and no upper limit/maximum since it is the number of correct items in 2 minutes. A higher score means better outcome.
Outcome measures
| Measure |
Donepezil HCL
n=12 Participants
Participants will receive 5mg of donepezil HCL for 4 weeks and then 10mg of donepezil HCL for 20 weeks.
donepezil HCL
|
Placebo
n=15 Participants
Participants will receive placebo for 24 weeks.
Placebo
|
Control Group
n=22 Participants
Participants without a family history of AD will undergo the study evaluations but will not receive any study drug
|
|---|---|---|---|
|
Processing Speed Test (PST) at 24 Weeks, Adjusted for Baseline PST Scores
|
44.17 Total number of correct items
Standard Deviation 7.96
|
49.8 Total number of correct items
Standard Deviation 4.69
|
47.73 Total number of correct items
Standard Deviation 4.87
|
Adverse Events
Donepezil HCL
Serious events: 0 serious events
Other events: 20 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
Control Group
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Donepezil HCL
n=28 participants at risk
Participants will receive 5mg of donepezil HCL for 4 weeks and then 10mg of donepezil HCL for 20 weeks.
donepezil HCL
|
Placebo
n=29 participants at risk
Participants will receive placebo for 24 weeks.
Placebo
|
Control Group
n=32 participants at risk
Participants without a family history of AD will undergo the study evaluations but will not receive any study drug
|
|---|---|---|---|
|
General disorders
Nausea
|
14.3%
4/28 • Number of events 4 • 6 Months
|
0.00%
0/29 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
General disorders
Dizziness
|
14.3%
4/28 • Number of events 4 • 6 Months
|
3.4%
1/29 • Number of events 1 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
Musculoskeletal and connective tissue disorders
Muscle cramping
|
25.0%
7/28 • Number of events 7 • 6 Months
|
3.4%
1/29 • Number of events 2 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
General disorders
Fatigue
|
10.7%
3/28 • Number of events 3 • 6 Months
|
0.00%
0/29 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
General disorders
Vivid dreams/Nightmares/Increased Dreams
|
35.7%
10/28 • Number of events 11 • 6 Months
|
3.4%
1/29 • Number of events 1 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
Gastrointestinal disorders
Loose stool/Diarrhea/Increased Bowel Movement
|
25.0%
7/28 • Number of events 7 • 6 Months
|
10.3%
3/29 • Number of events 3 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
Gastrointestinal disorders
Rumbling stomach
|
3.6%
1/28 • Number of events 1 • 6 Months
|
0.00%
0/29 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
General disorders
Disturbed sleep
|
25.0%
7/28 • Number of events 8 • 6 Months
|
0.00%
0/29 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
Ear and labyrinth disorders
Persistent ringing in ears
|
3.6%
1/28 • Number of events 1 • 6 Months
|
3.4%
1/29 • Number of events 1 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
Skin and subcutaneous tissue disorders
Recurrence of skin cancer
|
3.6%
1/28 • Number of events 1 • 6 Months
|
0.00%
0/29 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
General disorders
Decrease in appetite
|
3.6%
1/28 • Number of events 1 • 6 Months
|
6.9%
2/29 • Number of events 2 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
General disorders
Fall
|
7.1%
2/28 • Number of events 2 • 6 Months
|
0.00%
0/29 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
General disorders
Anxiety
|
7.1%
2/28 • Number of events 2 • 6 Months
|
0.00%
0/29 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
Eye disorders
Change in vision/Blurred vision
|
3.6%
1/28 • Number of events 1 • 6 Months
|
0.00%
0/29 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
General disorders
Mood changes/Mood swing
|
3.6%
1/28 • Number of events 1 • 6 Months
|
0.00%
0/29 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
Gastrointestinal disorders
Rectal Bleeding
|
3.6%
1/28 • Number of events 1 • 6 Months
|
0.00%
0/29 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
Renal and urinary disorders
Frequent urge to urinate
|
3.6%
1/28 • Number of events 1 • 6 Months
|
0.00%
0/29 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
General disorders
Increased talkativeness
|
3.6%
1/28 • Number of events 1 • 6 Months
|
0.00%
0/29 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
Cardiac disorders
Lower than normal heart rate
|
3.6%
1/28 • Number of events 1 • 6 Months
|
0.00%
0/29 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
Hepatobiliary disorders
Altered liver function tests
|
3.6%
1/28 • Number of events 1 • 6 Months
|
0.00%
0/29 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
Gastrointestinal disorders
Change in consistency of saliva
|
3.6%
1/28 • Number of events 1 • 6 Months
|
0.00%
0/29 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
Ear and labyrinth disorders
Vertigo
|
3.6%
1/28 • Number of events 1 • 6 Months
|
3.4%
1/29 • Number of events 1 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
General disorders
Headache/Pain in head or neck area
|
3.6%
1/28 • Number of events 1 • 6 Months
|
10.3%
3/29 • Number of events 3 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
General disorders
Excessive thirts
|
3.6%
1/28 • Number of events 1 • 6 Months
|
0.00%
0/29 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
Infections and infestations
Viral infection
|
0.00%
0/28 • 6 Months
|
3.4%
1/29 • Number of events 1 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
Reproductive system and breast disorders
Change in sexual intercourse or libido
|
0.00%
0/28 • 6 Months
|
3.4%
1/29 • Number of events 1 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
Musculoskeletal and connective tissue disorders
Hand surgery under general anesthesia
|
0.00%
0/28 • 6 Months
|
3.4%
1/29 • Number of events 1 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
Reproductive system and breast disorders
Scrotal blisters
|
0.00%
0/28 • 6 Months
|
3.4%
1/29 • Number of events 1 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
Nervous system disorders
Paresthesia in legs (numbness, tingling sensation)
|
0.00%
0/28 • 6 Months
|
3.4%
1/29 • Number of events 1 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
Skin and subcutaneous tissue disorders
Change in facial skin color (Darker skin in cheek area)
|
0.00%
0/28 • 6 Months
|
3.4%
1/29 • Number of events 1 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
Nervous system disorders
Increase in size of colloid cyst with early signs of hydrocephalus
|
0.00%
0/28 • 6 Months
|
3.4%
1/29 • Number of events 1 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
Skin and subcutaneous tissue disorders
Change in sweat/body smell
|
0.00%
0/28 • 6 Months
|
3.4%
1/29 • Number of events 1 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
Skin and subcutaneous tissue disorders
Eyebrows falling out
|
0.00%
0/28 • 6 Months
|
3.4%
1/29 • Number of events 2 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
Renal and urinary disorders
Kidney stones
|
0.00%
0/28 • 6 Months
|
3.4%
1/29 • Number of events 1 • 6 Months
|
0.00%
0/32 • 6 Months
|
|
Renal and urinary disorders
Urinary tract infection
|
0.00%
0/28 • 6 Months
|
3.4%
1/29 • Number of events 1 • 6 Months
|
0.00%
0/32 • 6 Months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place