Trial Outcomes & Findings for Olfactory Deficits and Donepezil Treatment in Cognitively Impaired Elderly (NCT NCT01951118)
NCT ID: NCT01951118
Last Updated: 2020-07-13
Results Overview
The Selective Reminding Test (SRT) is a 12-item test of verbal learning and memory. To administer, the researcher will read aloud a list of 12 words. The participant repeats each word aloud to ensure that the word was heard correctly. Immediately following the reading of all 12 words, the participant is asked to recall as many words as possible within the one minute time limit. The participant is then reminded of the words they did not say and asked to recall the list again. This process is repeated for 6 trials. The total immediate recall is the total number of words recalled by the participant from all 6 trials. This is the number that is reported. Lower scores indicate fewer words recalled and a poorer performance.
COMPLETED
PHASE4
121 participants
Week 0, Week 8, Week 26, Week 52
2020-07-13
Participant Flow
Participant milestones
| Measure |
Donepezil Treatment & Atropine Challenge
Atropine nasal spray is administered at baseline for the atropine challenge which involves administration of the 40-item UPSIT immediately before and 45 minutes after atropine administration. Immediately after the atropine challenge, donepezil treatment is started and continues for 52 weeks.
Donepezil: Donepezil 5mg will be given for 4 weeks and if tolerated, the dose will be increased to 10 mg per day. The dose range of 5 to 10 mg of donepezil per day will be continued for the study duration, and this is the recommended dose for donepezil in the treatment of mild to moderate Alzheimer's disease. For patients who do not tolerate donepezil or have a history of intolerance to donepezil or cannot take donepezil for other reasons, treatment with other cholinesterase inhibitors (galantamine or rivastigmine) is permitted at any stage of the protocol. Data will be analyzed in two ways: for donepezil alone, and for any cholinesterase inhibitor (donepezil or rivastigmine or galantamine).
|
|---|---|
|
Overall Study
STARTED
|
121
|
|
Overall Study
COMPLETED
|
94
|
|
Overall Study
NOT COMPLETED
|
27
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Olfactory Deficits and Donepezil Treatment in Cognitively Impaired Elderly
Baseline characteristics by cohort
| Measure |
Donepezil Treatment & Atropine Challenge
n=121 Participants
Atropine nasal spray is administered at baseline for the atropine challenge which involves administration of the 40-item UPSIT immediately before and 45 minutes after atropine administration. Immediately after the atropine challenge, donepezil treatment is started and continues for 52 weeks.
Donepezil: Donepezil 5mg will be given for 4 weeks and if tolerated, the dose will be increased to 10 mg per day. The dose range of 5 to 10 mg of donepezil per day will be continued for the study duration, and this is the recommended dose for donepezil in the treatment of mild to moderate Alzheimer's disease. For patients who do not tolerate donepezil or have a history of intolerance to donepezil or cannot take donepezil for other reasons, treatment with other cholinesterase inhibitors (galantamine or rivastigmine) is permitted at any stage of the protocol. Data will be analyzed in two ways: for donepezil alone, and for any cholinesterase inhibitor (donepezil or rivastigmine or galantamine).
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
40 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
81 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
61 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
60 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
21 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
100 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
5 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
|
27 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
88 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
121 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 0, Week 8, Week 26, Week 52Population: The number analyzed in one or more rows differs from overall number analyzed due to participant drop-out.
The Selective Reminding Test (SRT) is a 12-item test of verbal learning and memory. To administer, the researcher will read aloud a list of 12 words. The participant repeats each word aloud to ensure that the word was heard correctly. Immediately following the reading of all 12 words, the participant is asked to recall as many words as possible within the one minute time limit. The participant is then reminded of the words they did not say and asked to recall the list again. This process is repeated for 6 trials. The total immediate recall is the total number of words recalled by the participant from all 6 trials. This is the number that is reported. Lower scores indicate fewer words recalled and a poorer performance.
Outcome measures
| Measure |
MCI Sample
n=100 Participants
100 patients with MCI were analyzed for this sample.
|
AD Sample
n=21 Participants
21 patients with AD were analyzed for this sample.
|
|---|---|---|
|
Change Over Time in Selective Reminding Test (SRT) Scores
Week 0
|
36.14 Words
Standard Deviation 10.67
|
21.19 Words
Standard Deviation 8.23
|
|
Change Over Time in Selective Reminding Test (SRT) Scores
Week 8
|
39.99 Words
Standard Deviation 10.30
|
24.10 Words
Standard Deviation 9.82
|
|
Change Over Time in Selective Reminding Test (SRT) Scores
Week 26
|
39.75 Words
Standard Deviation 10.69
|
23.00 Words
Standard Deviation 8.07
|
|
Change Over Time in Selective Reminding Test (SRT) Scores
Week 52
|
39.62 Words
Standard Deviation 11.44
|
24.38 Words
Standard Deviation 9.69
|
SECONDARY outcome
Timeframe: Week 0, Week 8, Week 26, Week 52Population: The number analyzed in one or more rows differs from overall number analyzed due to participant drop-out.
The modified Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) is a cognitive battery that assesses learning, memory, language production, language comprehension, constructional praxis, ideational praxis, and orientation. The ADAS-Cog is not a timed test and the participant's score does not depend on how rapidly the test is completed. The ADAS-Cog total score is based on the total number of errors made in the test by the participant. Therefore, a lower total score indicates a higher cognitive performance. The total score ranges from 0 to 95 and is determined by summing the errors from 12 subscales. The total score, indicating number of errors made, is the number that is reported at each timeframe.
Outcome measures
| Measure |
MCI Sample
n=100 Participants
100 patients with MCI were analyzed for this sample.
|
AD Sample
n=21 Participants
21 patients with AD were analyzed for this sample.
|
|---|---|---|
|
Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog)
Week 0
|
11.41 Errors
Standard Deviation 4.67
|
21.67 Errors
Standard Deviation 6.12
|
|
Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog)
Week 8
|
10.13 Errors
Standard Deviation 4.22
|
19.30 Errors
Standard Deviation 5.80
|
|
Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog)
Week 26
|
9.63 Errors
Standard Deviation 4.44
|
19.63 Errors
Standard Deviation 7.15
|
|
Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog)
Week 52
|
10.40 Errors
Standard Deviation 4.72
|
22.69 Errors
Standard Deviation 8.99
|
SECONDARY outcome
Timeframe: Week 8, Week 26, Week 52Population: The number analyzed in one or more rows differs from overall number analyzed due to participant drop-out.
The CIBIC-plus is a well-validated, reliable and widely used measure (range 1-7) of global improvement used in AD and MCI trials. This is a measure of change based on clinician impression. Higher values represent a worse outcome.
Outcome measures
| Measure |
MCI Sample
n=100 Participants
100 patients with MCI were analyzed for this sample.
|
AD Sample
n=21 Participants
21 patients with AD were analyzed for this sample.
|
|---|---|---|
|
Clinician's Interview Based Impression (CIBIC-plus)
Week 8
|
3.34 units on a scale
Standard Deviation 0.74
|
3.55 units on a scale
Standard Deviation 0.69
|
|
Clinician's Interview Based Impression (CIBIC-plus)
Week 26
|
3.15 units on a scale
Standard Deviation 0.86
|
3.75 units on a scale
Standard Deviation 0.64
|
|
Clinician's Interview Based Impression (CIBIC-plus)
Week 52
|
3.11 units on a scale
Standard Deviation 1.17
|
4.38 units on a scale
Standard Deviation 0.96
|
SECONDARY outcome
Timeframe: Week 0, Week 8, Week 26, Week 52Population: The number analyzed in one or more rows differs from overall number analyzed due to participant drop-out.
FAQ is a widely used 10-item instrument that takes 3 minutes to administer and focuses on instrumental, social and cognitive functioning. The assessment is completed by a study informant - typically a caregiver able to report best on the patient's current ability. The instrument assesses the patient's current ability, at the point of testing and through the past month, in these various domains. The total score is described as the cumulative scores of each item, ranging from "0 - No help needed" to "3 - No, unable to do." More impairment is indicated by higher scores. The reported total score range is from 0 (no impairment score) to 30 (maximum impairment score).
Outcome measures
| Measure |
MCI Sample
n=100 Participants
100 patients with MCI were analyzed for this sample.
|
AD Sample
n=21 Participants
21 patients with AD were analyzed for this sample.
|
|---|---|---|
|
Pfeffer Functional Activities Questionnaire (FAQ)
Week 0
|
4.80 units on a scale
Standard Deviation 4.84
|
11.25 units on a scale
Standard Deviation 6.19
|
|
Pfeffer Functional Activities Questionnaire (FAQ)
Week 8
|
4.68 units on a scale
Standard Deviation 4.56
|
11.78 units on a scale
Standard Deviation 4.72
|
|
Pfeffer Functional Activities Questionnaire (FAQ)
Week 26
|
4.84 units on a scale
Standard Deviation 4.96
|
13.75 units on a scale
Standard Deviation 5.46
|
|
Pfeffer Functional Activities Questionnaire (FAQ)
Week 52
|
4.25 units on a scale
Standard Deviation 4.76
|
14.62 units on a scale
Standard Deviation 4.15
|
SECONDARY outcome
Timeframe: Week 0, Week 8, Week 26, Week 52Population: The number analyzed in one or more rows differs from overall number analyzed due to participant drop-out.
This instrument has 40 items, takes 20 minutes to administer, and focuses on functional correlates of cognitive deficits. This assessment asks the study informant to rate the participant's ability to perform certain tasks with the domains of Memory, Language, Visual-spatial and Perceptual Abilities, Executive Functioning: Planning, Executive Functioning: Organization, and Executive Functioning: Divided Attention. The informant is asked to compare functioning from 10 years prior to the time of testing. The Everyday Cognition measure uses the sum score of all of the subscales, and the items are reverse coded (i.e., 1= "Better or no change", 2="Questionable/occasionally worse", 3="Consistently a little worse", 4="Consistently much worse"), meaning that lower scores are better. Reported total scores range from 39 (Better or no change) to 156 (Consistently much worse).
Outcome measures
| Measure |
MCI Sample
n=100 Participants
100 patients with MCI were analyzed for this sample.
|
AD Sample
n=21 Participants
21 patients with AD were analyzed for this sample.
|
|---|---|---|
|
Measurement of Everyday Cognition (Ecog)
Week 0
|
67.93 units on a scale
Standard Deviation 20.58
|
90.80 units on a scale
Standard Deviation 28.11
|
|
Measurement of Everyday Cognition (Ecog)
Week 8
|
67.88 units on a scale
Standard Deviation 23.35
|
89.20 units on a scale
Standard Deviation 31.14
|
|
Measurement of Everyday Cognition (Ecog)
Week 26
|
67.92 units on a scale
Standard Deviation 23.20
|
97.65 units on a scale
Standard Deviation 29.02
|
|
Measurement of Everyday Cognition (Ecog)
Week 52
|
66.84 units on a scale
Standard Deviation 22.66
|
103.59 units on a scale
Standard Deviation 29.27
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Week 0, Week 26, Week 52Population: The number analyzed in one or more rows differs from overall number analyzed due to participant drop-out.
The Mini Mental State Examination (MMSE) is a widely used 30-item test of cognitive function that includes tests of orientation, attention, memory, language, and visual-spatial skills. Values range from 0-30; a higher value represents a better outcome.
Outcome measures
| Measure |
MCI Sample
n=100 Participants
100 patients with MCI were analyzed for this sample.
|
AD Sample
n=21 Participants
21 patients with AD were analyzed for this sample.
|
|---|---|---|
|
Mini-Mental State Examination - MMSE
Week 0
|
26.72 units on a scale
Standard Deviation 2.17
|
23.048 units on a scale
Standard Deviation 2.40
|
|
Mini-Mental State Examination - MMSE
Week 26
|
26.90 units on a scale
Standard Deviation 2.20
|
21.20 units on a scale
Standard Deviation 3.52
|
|
Mini-Mental State Examination - MMSE
Week 52
|
26.44 units on a scale
Standard Deviation 2.47
|
20.35 units on a scale
Standard Deviation 3.71
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Week 0, Week 52Parts A and B are composed of 25 circles. Patients are asked to scan the entire page and identify the next number or letter in a sequence.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Week 0, Week 52Population: The number analyzed in one or more rows differs from overall number analyzed due to participant drop-out.
The Wechsler Adult Intelligence Scale (WAIS) -III Digit Symbol Subtest is a paper-and-pencil cognitive test presented on a single sheet of paper that requires a subject to match symbols to numbers according to a key located on the top of the page. Values range from 0-93; a higher value represents a better outcome.
Outcome measures
| Measure |
MCI Sample
n=100 Participants
100 patients with MCI were analyzed for this sample.
|
AD Sample
n=21 Participants
21 patients with AD were analyzed for this sample.
|
|---|---|---|
|
Wechsler Adult Intelligence Scale (WAIS) -III Digit Symbol Subtest
Week 0
|
36.83 units on a scale
Standard Deviation 13.72
|
25.47 units on a scale
Standard Deviation 9.27
|
|
Wechsler Adult Intelligence Scale (WAIS) -III Digit Symbol Subtest
Week 52
|
37.24 units on a scale
Standard Deviation 12.17
|
21.06 units on a scale
Standard Deviation 11.66
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Week 0, Week 52Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Week 0, Week 52Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Week 0, Week 52.Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Week 0, Week 8, Week 26, Week 52Population: The number analyzed in one or more rows differs from overall number analyzed due to participant drop-out.
The Treatment Emergent Symptom Scale (TESS) is widely used to evaluate somatic side effects. For each item, a rating is made on a 3-point scale, with an additional rating on the likelihood that the medication caused the side effect. Values range from 0-78; a higher value indicates a worse outcome.
Outcome measures
| Measure |
MCI Sample
n=100 Participants
100 patients with MCI were analyzed for this sample.
|
AD Sample
n=21 Participants
21 patients with AD were analyzed for this sample.
|
|---|---|---|
|
Treatment Emergent Symptom Scale (TESS)
Week 52
|
1.28 units on a scale
Standard Deviation 2.11
|
1.69 units on a scale
Standard Deviation 2.33
|
|
Treatment Emergent Symptom Scale (TESS)
Week 0
|
2.57 units on a scale
Standard Deviation 2.62
|
1.89 units on a scale
Standard Deviation 2.05
|
|
Treatment Emergent Symptom Scale (TESS)
Week 8
|
1.61 units on a scale
Standard Deviation 1.90
|
1.53 units on a scale
Standard Deviation 1.37
|
|
Treatment Emergent Symptom Scale (TESS)
Week 26
|
1.42 units on a scale
Standard Deviation 1.86
|
1.20 units on a scale
Standard Deviation 1.47
|
Adverse Events
Donepezil Treatment & Atropine Challenge
Serious adverse events
| Measure |
Donepezil Treatment & Atropine Challenge
n=121 participants at risk
Atropine nasal spray is administered at baseline for the atropine challenge which involves administration of the 40-item UPSIT immediately before and 45 minutes after atropine administration. Immediately after the atropine challenge, donepezil treatment is started and continues for 52 weeks.
Donepezil: Donepezil 5mg will be given for 4 weeks and if tolerated, the dose will be increased to 10 mg per day. The dose range of 5 to 10 mg of donepezil per day will be continued for the study duration, and this is the recommended dose for donepezil in the treatment of mild to moderate Alzheimer's disease. For patients who do not tolerate donepezil or have a history of intolerance to donepezil or cannot take donepezil for other reasons, treatment with other cholinesterase inhibitors (galantamine or rivastigmine) is permitted at any stage of the protocol. Data will be analyzed in two ways: for donepezil alone, and for any cholinesterase inhibitor (donepezil or rivastigmine or galantamine).
|
|---|---|
|
Blood and lymphatic system disorders
Low platelet level
|
0.83%
1/121 • Adverse event data were collected beginning at study start through study conclusion, an average of 5 years.
|
|
Musculoskeletal and connective tissue disorders
Broken Femur
|
0.83%
1/121 • Adverse event data were collected beginning at study start through study conclusion, an average of 5 years.
|
|
Psychiatric disorders
Agitation
|
0.83%
1/121 • Adverse event data were collected beginning at study start through study conclusion, an average of 5 years.
|
|
General disorders
Dizziness
|
0.83%
1/121 • Adverse event data were collected beginning at study start through study conclusion, an average of 5 years.
|
|
Musculoskeletal and connective tissue disorders
Wrist Fracture
|
0.83%
1/121 • Adverse event data were collected beginning at study start through study conclusion, an average of 5 years.
|
|
General disorders
Death
|
2.5%
3/121 • Adverse event data were collected beginning at study start through study conclusion, an average of 5 years.
|
Other adverse events
Adverse event data not reported
Additional Information
Dr. Davangere Devanand
New York State Psychiatric Institute
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place