Trial Outcomes & Findings for Olfactory Deficits in MCI as Predictor of Improved Cognition on Donepezil (NCT NCT01845636)
NCT ID: NCT01845636
Last Updated: 2018-07-09
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
41 participants
Week 0, Week 8, Week 26, Week 52
2018-07-09
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 University of Pennsylvania Smell Identification Test (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.
Atropine: A single acute dose of 1 mg of atropine nasal spray is administered to the nostril. The dose chosen reflects clinical doses typically used by Ear, Nose, and Throat (ENT) physicians.
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Overall Study
STARTED
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41
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Overall Study
COMPLETED
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37
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Overall Study
NOT COMPLETED
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4
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Olfactory Deficits in MCI as Predictor of Improved Cognition on Donepezil
Baseline characteristics by cohort
| Measure |
Donepezil Treatment & Atropine Challenge
n=37 Participants
Atropine nasal spray is administered at baseline for the atropine challenge which involves administration of the 40-item University of Pennsylvania Smell Identification Test (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.
Atropine: A single acute dose of 1 mg of atropine nasal spray is administered to the nostril. The dose chosen reflects clinical doses typically used by Ear, Nose, and Throat (ENT) physicians.
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Age, Categorical
<=18 years
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0 Participants
n=5 Participants
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Age, Categorical
Between 18 and 65 years
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8 Participants
n=5 Participants
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Age, Categorical
>=65 years
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29 Participants
n=5 Participants
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Age, Continuous
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70.4 years
STANDARD_DEVIATION 9.8 • n=5 Participants
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Sex: Female, Male
Female
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17 Participants
n=5 Participants
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Sex: Female, Male
Male
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20 Participants
n=5 Participants
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Region of Enrollment
United States
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37 Participants
n=5 Participants
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Selective Reminding Test Total Recall Score
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33.61 Words
STANDARD_DEVIATION 8.15 • n=5 Participants
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PRIMARY outcome
Timeframe: Week 0, Week 8, Week 26, Week 52The 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 |
Donepezil Treatment & Atropine Challenge
n=37 Participants
Atropine nasal spray is administered at baseline for the atropine challenge which involves administration of the 40-item University of Pennsylvania Smell Identification Test (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.
Atropine: A single acute dose of 1 mg of atropine nasal spray is administered to the nostril. The dose chosen reflects clinical doses typically used by Ear, Nose, and Throat (ENT) physicians.
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Selective Reminding Test (SRT)
Week 26
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36.81 Words
Standard Deviation 9.22
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Selective Reminding Test (SRT)
Week 0
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33.61 Words
Standard Deviation 8.15
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Selective Reminding Test (SRT)
Week 8
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36.23 Words
Standard Deviation 9.27
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Selective Reminding Test (SRT)
Week 52
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37.13 Words
Standard Deviation 10.59
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SECONDARY outcome
Timeframe: Week 0, Week 8, Week 26, Week 52The 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 |
Donepezil Treatment & Atropine Challenge
n=37 Participants
Atropine nasal spray is administered at baseline for the atropine challenge which involves administration of the 40-item University of Pennsylvania Smell Identification Test (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.
Atropine: A single acute dose of 1 mg of atropine nasal spray is administered to the nostril. The dose chosen reflects clinical doses typically used by Ear, Nose, and Throat (ENT) physicians.
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Total Number of Errors Measured Using the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog)
Week 0
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10.67 Errors
Standard Deviation 4.15
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Total Number of Errors Measured Using the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog)
Week 8
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10.27 Errors
Standard Deviation 3.83
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Total Number of Errors Measured Using the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog)
Week 26
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8.80 Errors
Standard Deviation 3.69
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Total Number of Errors Measured Using the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog)
Week 52
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10.09 Errors
Standard Deviation 4.68
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SECONDARY outcome
Timeframe: Week 0, Week 4, Week 8, Week 26, Week 52FAQ 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 |
Donepezil Treatment & Atropine Challenge
n=37 Participants
Atropine nasal spray is administered at baseline for the atropine challenge which involves administration of the 40-item University of Pennsylvania Smell Identification Test (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.
Atropine: A single acute dose of 1 mg of atropine nasal spray is administered to the nostril. The dose chosen reflects clinical doses typically used by Ear, Nose, and Throat (ENT) physicians.
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Pfeffer Functional Activities Questionnaire (FAQ)
Week 52
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5.16 units on a scale
Standard Deviation 5.36
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Pfeffer Functional Activities Questionnaire (FAQ)
Week 0
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3.73 units on a scale
Standard Deviation 4.17
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Pfeffer Functional Activities Questionnaire (FAQ)
Week 8
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4.37 units on a scale
Standard Deviation 4.72
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Pfeffer Functional Activities Questionnaire (FAQ)
Week 26
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4.40 units on a scale
Standard Deviation 4.74
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SECONDARY outcome
Timeframe: Week 0, Week 4, Week 8, Week 26, Week 52This 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 |
Donepezil Treatment & Atropine Challenge
n=37 Participants
Atropine nasal spray is administered at baseline for the atropine challenge which involves administration of the 40-item University of Pennsylvania Smell Identification Test (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.
Atropine: A single acute dose of 1 mg of atropine nasal spray is administered to the nostril. The dose chosen reflects clinical doses typically used by Ear, Nose, and Throat (ENT) physicians.
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Measurement of Everyday Cognition (Ecog)
Week 0
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60.27 units on a scale
Standard Deviation 23.13
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Measurement of Everyday Cognition (Ecog)
Week 8
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62.80 units on a scale
Standard Deviation 27.91
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Measurement of Everyday Cognition (Ecog)
Week 26
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63.37 units on a scale
Standard Deviation 28.93
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Measurement of Everyday Cognition (Ecog)
Week 52
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65.39 units on a scale
Standard Deviation 29.53
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SECONDARY outcome
Timeframe: Week 8, Week 26, Week 52The 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.
Outcome measures
| Measure |
Donepezil Treatment & Atropine Challenge
n=37 Participants
Atropine nasal spray is administered at baseline for the atropine challenge which involves administration of the 40-item University of Pennsylvania Smell Identification Test (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.
Atropine: A single acute dose of 1 mg of atropine nasal spray is administered to the nostril. The dose chosen reflects clinical doses typically used by Ear, Nose, and Throat (ENT) physicians.
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Clinician's Interview Based Impression of Change Plus Caregiver Input (CIBIC-plus)
Week 8
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3.43 units on a scale
Standard Deviation 0.7
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Clinician's Interview Based Impression of Change Plus Caregiver Input (CIBIC-plus)
Week 26
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3.31 units on a scale
Standard Deviation 0.74
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Clinician's Interview Based Impression of Change Plus Caregiver Input (CIBIC-plus)
Week 52
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3.13 units on a scale
Standard Deviation 1.18
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Adverse Events
Donepezil Treatment & Atropine Challenge
Serious adverse events
| Measure |
Donepezil Treatment & Atropine Challenge
n=41 participants at risk
Atropine nasal spray is administered at baseline for the atropine challenge which involves administration of the 40-item University of Pennsylvania Smell Identification Test (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.
Atropine: A single acute dose of 1 mg of atropine nasal spray is administered to the nostril. The dose chosen reflects clinical doses typically used by Ear, Nose, and Throat (ENT) physicians.
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Psychiatric disorders
Alcohol abuse
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2.4%
1/41 • Adverse event data were collected beginning at study start in August 2012 and ending at study conclusion in March 2016.
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Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer
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2.4%
1/41 • Adverse event data were collected beginning at study start in August 2012 and ending at study conclusion in March 2016.
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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