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
|Condition or disease||Intervention/treatment||Phase|
|Alzheimer Disease Mild Cognitive Impairment Delirium, Dementia, Amnestic, Cognitive Disorders||Drug: Donepezil||Phase 4|
In this clinical trial, the investigators will evaluate, treat and follow two broad samples of adult patients at New York State Psychiatric Institute/Columbia University Medical Center. Study 1 will include 70 patients with amnestic Mild Cognitive Impairment (MCI). Study 2 will include 100 patients with probable Alzheimer's Disease (AD). Recruitment will be from clinics and/or advertisements. In the protocol, all 170 patients will receive baseline memory and olfactory assessments and are treated with donepezil. Patients will be followed for a total of 1 year. During this time, patients will be monitored closely by the study physician and will receive memory and olfactory assessments at weeks 0, 8, 26, and 52. In addition, an olfactory challenge test will be done at baseline.
This project will be of value in the selection of patients with MCI and AD for treatment based on the evaluation of olfaction tests to predict response to donepezil. Since mild cognitive impairment is widespread and Alzheimer's disease represents a major public health problem, this study has considerable public purpose and significance.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||121 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Olfactory Deficits and Donepezil Treatment in Cognitively Impaired Elderly|
|Actual Study Start Date :||October 2013|
|Actual Primary Completion Date :||May 2019|
|Actual Study Completion Date :||May 2019|
Experimental: 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 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) as the intervention.
Other Name: Aricept
- Change Over Time in Selective Reminding Test (SRT) Scores [ Time Frame: Week 0, Week 8, Week 26, Week 52 ]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.
- Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) [ Time Frame: Week 0, Week 8, Week 26, Week 52 ]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.
- Clinician's Interview Based Impression (CIBIC-plus) [ Time Frame: Week 8, Week 26, Week 52 ]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.
- Pfeffer Functional Activities Questionnaire (FAQ) [ Time Frame: Week 0, Week 8, Week 26, Week 52 ]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).
- Measurement of Everyday Cognition (Ecog) [ Time Frame: Week 0, Week 8, Week 26, Week 52 ]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).
- Mini-Mental State Examination - MMSE [ Time Frame: Week 0, Week 26, Week 52 ]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.
- Trail Making Test (Parts A and B) [ Time Frame: Week 0, Week 52 ]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.
- Wechsler Adult Intelligence Scale (WAIS) -III Digit Symbol Subtest [ Time Frame: Week 0, Week 52 ]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.
- Controlled Word Association (CFL) [ Time Frame: Week 0, Week 52 ]
- Boston Naming Test (BNT) [ Time Frame: Week 0, Week 52 ]
- Wechsler Memory Scale (WMS)-R Digit Span [ Time Frame: Week 0, Week 52. ]
- Treatment Emergent Symptom Scale (TESS) [ Time Frame: Week 0, Week 8, Week 26, Week 52 ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01951118
|United States, New York|
|New York State Psychiatric Institute|
|New York, New York, United States, 10032|
|Principal Investigator:||Davangere Devanand, M.D.||Columbia University|