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Olfactory Deficits and Donepezil Treatment in Cognitively Impaired Elderly

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ClinicalTrials.gov Identifier: NCT01951118
Recruitment Status : Completed
First Posted : September 26, 2013
Results First Posted : July 13, 2020
Last Update Posted : July 13, 2020
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Davangere P. Devanand, New York State Psychiatric Institute

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Conditions Alzheimer Disease
Mild Cognitive Impairment
Delirium, Dementia, Amnestic, Cognitive Disorders
Intervention Drug: Donepezil
Enrollment 121
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Donepezil Treatment & Atropine Challenge
Hide Arm/Group Description

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).

Period Title: Overall Study
Started 121
Completed 94
Not Completed 27
Arm/Group Title Donepezil Treatment & Atropine Challenge
Hide Arm/Group Description

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 Number of Baseline Participants 121
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 121 participants
<=18 years
0
   0.0%
Between 18 and 65 years
40
  33.1%
>=65 years
81
  66.9%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 121 participants
Female
61
  50.4%
Male
60
  49.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 121 participants
Hispanic or Latino
21
  17.4%
Not Hispanic or Latino
100
  82.6%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 121 participants
American Indian or Alaska Native
0
   0.0%
Asian
5
   4.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
27
  22.3%
White
88
  72.7%
More than one race
1
   0.8%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 121 participants
121
1.Primary Outcome
Title Change Over Time in Selective Reminding Test (SRT) Scores
Hide Description 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.
Time Frame Week 0, Week 8, Week 26, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The number analyzed in one or more rows differs from overall number analyzed due to participant drop-out.
Arm/Group Title MCI Sample AD Sample
Hide Arm/Group Description:
100 patients with MCI were analyzed for this sample.
21 patients with AD were analyzed for this sample.
Overall Number of Participants Analyzed 100 21
Mean (Standard Deviation)
Unit of Measure: Words
Week 0 Number Analyzed 100 participants 21 participants
36.14  (10.67) 21.19  (8.23)
Week 8 Number Analyzed 90 participants 20 participants
39.99  (10.30) 24.10  (9.82)
Week 26 Number Analyzed 83 participants 20 participants
39.75  (10.69) 23.00  (8.07)
Week 52 Number Analyzed 77 participants 16 participants
39.62  (11.44) 24.38  (9.69)
2.Secondary Outcome
Title Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog)
Hide Description 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.
Time Frame Week 0, Week 8, Week 26, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The number analyzed in one or more rows differs from overall number analyzed due to participant drop-out.
Arm/Group Title MCI Sample AD Sample
Hide Arm/Group Description:
100 MCI participants were analyzed for this sample.
21 AD participants were analyzed for this sample.
Overall Number of Participants Analyzed 100 21
Mean (Standard Deviation)
Unit of Measure: Errors
Week 0 Number Analyzed 99 participants 21 participants
11.41  (4.67) 21.67  (6.12)
Week 8 Number Analyzed 89 participants 20 participants
10.13  (4.22) 19.30  (5.80)
Week 26 Number Analyzed 83 participants 20 participants
9.63  (4.44) 19.63  (7.15)
Week 52 Number Analyzed 77 participants 15 participants
10.40  (4.72) 22.69  (8.99)
3.Secondary Outcome
Title Clinician's Interview Based Impression (CIBIC-plus)
Hide Description 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.
Time Frame Week 8, Week 26, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The number analyzed in one or more rows differs from overall number analyzed due to participant drop-out.
Arm/Group Title MCI Sample AD Sample
Hide Arm/Group Description:
100 MCI participants were analyzed for this sample.
21 AD participants were analyzed for this sample.
Overall Number of Participants Analyzed 100 21
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 8 Number Analyzed 89 participants 20 participants
3.34  (0.74) 3.55  (0.69)
Week 26 Number Analyzed 82 participants 20 participants
3.15  (0.86) 3.75  (0.64)
Week 52 Number Analyzed 76 participants 16 participants
3.11  (1.17) 4.38  (0.96)
4.Secondary Outcome
Title Pfeffer Functional Activities Questionnaire (FAQ)
Hide Description 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).
Time Frame Week 0, Week 8, Week 26, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The number analyzed in one or more rows differs from overall number analyzed due to participant drop-out.
Arm/Group Title MCI Sample AD Sample
Hide Arm/Group Description:
100 MCI participants were analyzed for this sample.
21 AD participants were analyzed for this sample.
Overall Number of Participants Analyzed 100 21
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 0 Number Analyzed 94 participants 16 participants
4.80  (4.84) 11.25  (6.19)
Week 8 Number Analyzed 83 participants 18 participants
4.68  (4.56) 11.78  (4.72)
Week 26 Number Analyzed 77 participants 20 participants
4.84  (4.96) 13.75  (5.46)
Week 52 Number Analyzed 74 participants 13 participants
4.25  (4.76) 14.62  (4.15)
5.Secondary Outcome
Title Measurement of Everyday Cognition (Ecog)
Hide Description 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).
Time Frame Week 0, Week 8, Week 26, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The number analyzed in one or more rows differs from overall number analyzed due to participant drop-out.
Arm/Group Title MCI Sample AD Sample
Hide Arm/Group Description:
100 MCI participants were included in this sample.
21 AD participants were included in this sample.
Overall Number of Participants Analyzed 100 21
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 0 Number Analyzed 92 participants 20 participants
67.93  (20.58) 90.80  (28.11)
Week 8 Number Analyzed 83 participants 20 participants
67.88  (23.35) 89.20  (31.14)
Week 26 Number Analyzed 77 participants 20 participants
67.92  (23.20) 97.65  (29.02)
Week 52 Number Analyzed 74 participants 17 participants
66.84  (22.66) 103.59  (29.27)
6.Other Pre-specified Outcome
Title Mini-Mental State Examination - MMSE
Hide Description 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.
Time Frame Week 0, Week 26, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The number analyzed in one or more rows differs from overall number analyzed due to participant drop-out.
Arm/Group Title MCI Sample AD Sample
Hide Arm/Group Description:
100 MCI participants were included in this sample.
21 AD participants were included in this sample.
Overall Number of Participants Analyzed 100 21
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 0 Number Analyzed 100 participants 21 participants
26.72  (2.17) 23.048  (2.40)
Week 26 Number Analyzed 83 participants 20 participants
26.90  (2.20) 21.20  (3.52)
Week 52 Number Analyzed 77 participants 17 participants
26.44  (2.47) 20.35  (3.71)
7.Other Pre-specified Outcome
Title Trail Making Test (Parts A and B)
Hide Description Parts 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.
Time Frame Week 0, Week 52
Outcome Measure Data Not Reported
8.Other Pre-specified Outcome
Title Wechsler Adult Intelligence Scale (WAIS) -III Digit Symbol Subtest
Hide Description 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.
Time Frame Week 0, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The number analyzed in one or more rows differs from overall number analyzed due to participant drop-out.
Arm/Group Title MCI Sample AD Sample
Hide Arm/Group Description:
100 MCI participants were included in this sample.
21 AD participants were included in this sample.
Overall Number of Participants Analyzed 100 21
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 0 Number Analyzed 99 participants 19 participants
36.83  (13.72) 25.47  (9.27)
Week 52 Number Analyzed 76 participants 16 participants
37.24  (12.17) 21.06  (11.66)
9.Other Pre-specified Outcome
Title Controlled Word Association (CFL)
Hide Description [Not Specified]
Time Frame Week 0, Week 52
Outcome Measure Data Not Reported
10.Other Pre-specified Outcome
Title Boston Naming Test (BNT)
Hide Description [Not Specified]
Time Frame Week 0, Week 52
Outcome Measure Data Not Reported
11.Other Pre-specified Outcome
Title Wechsler Memory Scale (WMS)-R Digit Span
Hide Description [Not Specified]
Time Frame Week 0, Week 52.
Outcome Measure Data Not Reported
12.Other Pre-specified Outcome
Title Treatment Emergent Symptom Scale (TESS)
Hide Description 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.
Time Frame Week 0, Week 8, Week 26, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The number analyzed in one or more rows differs from overall number analyzed due to participant drop-out.
Arm/Group Title MCI Sample AD Sample
Hide Arm/Group Description:
100 MCI participants were analyzed for this sample.
21 AD participants were analyzed for this sample.
Overall Number of Participants Analyzed 100 21
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 0 Number Analyzed 98 participants 18 participants
2.57  (2.62) 1.89  (2.05)
Week 8 Number Analyzed 88 participants 17 participants
1.61  (1.90) 1.53  (1.37)
Week 26 Number Analyzed 77 participants 20 participants
1.42  (1.86) 1.20  (1.47)
Week 52 Number Analyzed 74 participants 16 participants
1.28  (2.11) 1.69  (2.33)
Time Frame Adverse event data were collected beginning at study start through study conclusion, an average of 5 years.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Donepezil Treatment & Atropine Challenge
Hide Arm/Group Description

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).

All-Cause Mortality
Donepezil Treatment & Atropine Challenge
Affected / at Risk (%)
Total   3/121 (2.48%) 
Hide Serious Adverse Events
Donepezil Treatment & Atropine Challenge
Affected / at Risk (%)
Total   8/121 (6.61%) 
Blood and lymphatic system disorders   
Low platelet level *  1/121 (0.83%) 
General disorders   
Dizziness *  1/121 (0.83%) 
Death *  3/121 (2.48%) 
Musculoskeletal and connective tissue disorders   
Broken Femur *  1/121 (0.83%) 
Wrist Fracture *  1/121 (0.83%) 
Psychiatric disorders   
Agitation *  1/121 (0.83%) 
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Donepezil Treatment & Atropine Challenge
Affected / at Risk (%)
Total   0/121 (0.00%) 
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Davangere Devanand
Organization: New York State Psychiatric Institute
Phone: 646-774-8658
EMail: dpd3@cumc.columbia.edu
Layout table for additonal information
Responsible Party: Davangere P. Devanand, New York State Psychiatric Institute
ClinicalTrials.gov Identifier: NCT01951118    
Other Study ID Numbers: 6655
1R01AG041795 ( U.S. NIH Grant/Contract )
First Submitted: September 18, 2013
First Posted: September 26, 2013
Results First Submitted: May 29, 2020
Results First Posted: July 13, 2020
Last Update Posted: July 13, 2020