Olfactory Deficits in MCI as Predictor of Improved Cognition on Donepezil
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Olfactory Deficits in Mild Cognitive Impairment as a Predictor of Improved Cognition on Donepezil|
- Selective Reminding Test (SRT) [ Time Frame: Week 0, Week 8, Week 26, Week 52 ] [ Designated as safety issue: No ]The 12-item, 6-trial SRT is a memory measure used to assess verbal list learning and memory. The total number of words learned over six trials (total immediate recall), and delayed recall (after a 15-minute delay) will be obtained.
- Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) [ Time Frame: Week 0, Week 8, Week 26, Week 52 ] [ Designated as safety issue: No ]The modified ADAS-Cog is a cognitive battery that assesses learning, memory, language production, language comprehension, constructional praxis, ideational praxis, and orientation.
- Pfeffer Functional Activities Questionnaire (FAQ) [ Time Frame: Week 0, Week 4, Week 8, Week 26, Week 52 ] [ Designated as safety issue: No ]FAQ is a widely used 10-item instrument that takes 3 minutes to administer and focuses on instrumental, social and cognitive functioning.
- Measurement of Everyday Cognition (Ecog) [ Time Frame: Week 0, Week 4, Week 8, Week 26, Week 52 ] [ Designated as safety issue: No ]This instrument has 40 items, takes 20 minutes to administer, and focuses on functional correlates of cognitive deficits.
- Clinician's Interview Based Impression of Change plus Caregiver Input (CIBIC-plus) [ Time Frame: Week 0, Week 2, Week 4, Week 8, Week 26, Week 52 ] [ Designated as safety issue: No ]The CIBIC-plus is a well-validated, reliable and widely used measure (range 1-7) of global improvement used in AD and MCI trials.
- Mini-Mental State Examination - MMSE [ Time Frame: Week 0, Week 26, Week 52 ] [ Designated as safety issue: No ]
- Trail Making Test (Parts A and B) [ Time Frame: Week 0, Week 52 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]
- Controlled Word Association (CFL) [ Time Frame: Week 0, Week 52 ] [ Designated as safety issue: No ]
- Boston Naming Test (BNT) [ Time Frame: Week 0, Week 52 ] [ Designated as safety issue: No ]
- Wechsler Memory Scale (WMS)-R Digit Span [ Time Frame: Week 0, Week 52 ] [ Designated as safety issue: No ]
- Treatment Emergent Symptom Scale (TESS) [ Time Frame: Week 0, Week 4, Week 8, Week 26, Week 52 ] [ Designated as safety issue: No ]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.
|Study Start Date:||August 2012|
|Estimated Study Completion Date:||March 2016|
|Estimated Primary Completion Date:||March 2016 (Final data collection date for primary outcome measure)|
Experimental: 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 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.
Other Name: AriceptDrug: 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.
Other Name: Atropine sulfate ophthalmic solution 1%
In this clinical trial, the investigators will evaluate, treat and follow a broad sample of 60 adult patients with amnestic MCI at New York State Psychiatric Institute/Columbia University Medical Center. Recruitment will be from clinics and/or advertisements. In the protocol, all 60 amnestic MCI patients will receive baseline memory and olfactory assessments and begin treatment 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 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 mild cognitive impairment for treatment based on the evaluation of olfaction tests to predict response to donepezil and other ACheI. Since mild cognitive impairment is widespread and Alzheimer's disease represents a major public health problem, this study has considerable public purpose and significance.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01845636
|United States, New York|
|New York State Psychiatric Institute|
|New York, New York, United States, 10032|
|Principal Investigator:||Davangere Devanand, M.D.||Columbia University|
|Study Director:||Gregory Pelton, M.D.||Columbia University|