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Trial record 65 of 331 for:    DONEPEZIL

Olfactory Deficits in MCI as Predictor of Improved Cognition on Donepezil

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ClinicalTrials.gov Identifier: NCT01845636
Recruitment Status : Completed
First Posted : May 3, 2013
Results First Posted : March 13, 2018
Last Update Posted : July 9, 2018
Sponsor:
Collaborator:
United States Department of Defense
Information provided by (Responsible Party):
Davangere P. Devanand, New York State Psychiatric Institute

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Mild Cognitive Impairment
Interventions Drug: Donepezil
Drug: Atropine
Enrollment 41
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 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.

Period Title: Overall Study
Started 41
Completed 37
Not Completed 4
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 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.

Overall Number of Baseline Participants 37
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants
<=18 years
0
   0.0%
Between 18 and 65 years
8
  21.6%
>=65 years
29
  78.4%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 37 participants
70.4  (9.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants
Female
17
  45.9%
Male
20
  54.1%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 37 participants
37
 100.0%
Selective Reminding Test Total Recall Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Words
Number Analyzed 37 participants
33.61  (8.15)
[1]
Measure 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 for all 6 trials is the number that is reported.
1.Primary Outcome
Title Selective Reminding Test (SRT)
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
[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 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.

Overall Number of Participants Analyzed 37
Mean (Standard Deviation)
Unit of Measure: Words
Week 0 33.61  (8.15)
Week 8 36.23  (9.27)
Week 26 36.81  (9.22)
Week 52 37.13  (10.59)
2.Secondary Outcome
Title Total Number of Errors Measured Using the 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
[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 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.

Overall Number of Participants Analyzed 37
Mean (Standard Deviation)
Unit of Measure: Errors
Week 0 10.67  (4.15)
Week 8 10.27  (3.83)
Week 26 8.80  (3.69)
Week 52 10.09  (4.68)
3.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 4, Week 8, Week 26, Week 52
Hide Outcome Measure Data
Hide Analysis Population 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 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.

Overall Number of Participants Analyzed 37
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 0 3.73  (4.17)
Week 8 4.37  (4.72)
Week 26 4.40  (4.74)
Week 52 5.16  (5.36)
4.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 4, Week 8, Week 26, Week 52
Hide Outcome Measure Data
Hide Analysis Population 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 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.

Overall Number of Participants Analyzed 37
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 0 60.27  (23.13)
Week 8 62.80  (27.91)
Week 26 63.37  (28.93)
Week 52 65.39  (29.53)
5.Secondary Outcome
Title Clinician's Interview Based Impression of Change Plus Caregiver Input (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.
Time Frame Week 8, Week 26, Week 52
Hide Outcome Measure Data
Hide Analysis Population 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 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.

Overall Number of Participants Analyzed 37
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 8 3.43  (0.7)
Week 26 3.31  (0.74)
Week 52 3.13  (1.18)
Time Frame Adverse event data were collected beginning at study start in August 2012 and ending at study conclusion in March 2016.
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 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.

All-Cause Mortality
Donepezil Treatment & Atropine Challenge
Affected / at Risk (%)
Total   0/41 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Donepezil Treatment & Atropine Challenge
Affected / at Risk (%)
Total   2/41 (4.88%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Cancer   1/41 (2.44%) 
Psychiatric disorders   
Alcohol abuse   1/41 (2.44%) 
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Donepezil Treatment & Atropine Challenge
Affected / at Risk (%)
Total   0/41 (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: NCT01845636     History of Changes
Other Study ID Numbers: 6577
W81XWH-12-0142 ( Other Grant/Funding Number: DOD and TATRC )
First Submitted: April 26, 2013
First Posted: May 3, 2013
Results First Submitted: July 3, 2017
Results First Posted: March 13, 2018
Last Update Posted: July 9, 2018