Olfactory Deficits in MCI as Predictor of Improved Cognition on Donepezil

NCT01845636 | Completed Phase 4 Results DMC

• 2 other identifiers: 6577W81XWH-12-0142
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

Odor identification deficits, which are a result of early Alzheimer's Disease (AD) pathology in the olfactory bulb and tract as well as olfactory projection areas in the medial temporal lobe (entorhinal and piriform cortex and hippocampus), lateral and central orbitofrontal cortex and several other regions, occur in AD and strongly predict mild cognitive impairment (MCI) conversion to AD. Our pilot data, along with converging findings in the literature, suggests that odor identification deficits, both incremental change over time and change in response to an anticholinergic challenge, may be clinically simple, relatively inexpensive, predictors of cognitive improvement with acetylcholinesterase inhibitor (ACheI) treatment with potential clinical implications for predicting improvement and monitoring ACheI therapy.

Conditions

Mild Cognitive Impairment

Keywords

Olfaction; Donepezil; Alzheimer's Disease; Mild Cognitive Impairment; Memory

Outcome Measures

Primary Outcomes (1)

• Selective Reminding Test (SRT)

  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.

  Week 0, Week 8, Week 26, Week 52

Secondary Outcomes (4)

• Total Number of Errors Measured Using the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog)

  Week 0, Week 8, Week 26, Week 52

• Pfeffer Functional Activities Questionnaire (FAQ)

  Week 0, Week 4, Week 8, Week 26, Week 52

• Measurement of Everyday Cognition (Ecog)

  Week 0, Week 4, Week 8, Week 26, Week 52

• Clinician's Interview Based Impression of Change Plus Caregiver Input (CIBIC-plus)

  Week 8, Week 26, Week 52

Study Arms (1)

Donepezil Treatment & Atropine Challenge

EXPERIMENTAL

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.

Drug: Donepezil; Drug: Atropine

Interventions

Donepezil DRUG

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.

Also known as: Aricept

Donepezil Treatment & Atropine Challenge

Atropine DRUG

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.

Also known as: Atropine sulfate ophthalmic solution 1%

Donepezil Treatment & Atropine Challenge

Eligibility Criteria

• Age: 55 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Of either sex, age 55-95 years old
• Patients who meet criteria for amnestic mild cognitive impairment by meeting all of the following:
• (i) subjective memory complaints (ii) Wechsler Memory Scale-R Logical Memory combined Story A + B immediate recall score or combined Story A + B delayed recall score or Free and Cued Selective Reminding Test immediate recall or delayed recall score greater than 1.5 Standard Deviation (SD) below norms or Selective Reminding Test immediate recall or delayed recall score greater than 1.5 SD below norms iii) no functional impairment consistent with dementia
• Folstein Mini Mental State (MMSE) score ≥ 23 out of 30
• Clinical Dementia Rating (CDR) of 0.5 (questionable dementia)
• Availability of informant

You may not qualify if:

• Meets Criteria for dementia by Diagnostic and Statistical Manual IV (DSM-IV) criteria or probable Alzheimer's disease
• Meets DSM IV criteria for:
• (i)schizophrenia, schizoaffective disorder, other psychosis, or bipolar I disorder (ii)alcohol or substance dependence or abuse (current or within past 6 months)
• Current untreated major depression or suicidality
• Parkinson's disease, Lewy body disease, multiple sclerosis, central nervous system infection, Huntington's disease, amyotrophic lateral sclerosis, other major neurological disorder.
• Mental Retardation
• Patients receiving cholinesterase inhibitors (donepezil, rivastigmine, galantamine) or memantine will be excluded.
• Medical contraindication to donepezil treatment or prior history of intolerability to donepezil treatment.
• Medications with anticholinergic effects that have been shown to adversely impact cognition will not be permitted. Benzodiazepines in lorazepam equivalents greater than or equal to 2 mg daily and narcotics will also not be permitted.

Sponsors & Collaborators

• New York State Psychiatric Institute: lead
• United States Department of Defense: collaborator

Study Sites (1)

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Cognitive Dysfunction; Anosmia; Alzheimer Disease

Interventions

Donepezil; Atropine

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Olfaction Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Dementia; Brain Diseases; Central Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds; Atropine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Belladonna Alkaloids; Solanaceous Alkaloids; Alkaloids; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

• Title: Dr. Davangere Devanand
• Organization: New York State Psychiatric Institute

dpd3@cumc.columbia.edu

646-774-8658

Study Officials

• Davangere Devanand, M.D.

  Columbia University

  PRINCIPAL INVESTIGATOR

• Gregory Pelton, M.D.

  Columbia University

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Clinical Psychiatry and Neurology

Study Record Dates

• First Submitted: April 26, 2013
• First Posted: May 3, 2013
• Study Start: August 1, 2012
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: July 9, 2018
• Results First Posted: March 13, 2018

Record last verified: 2018-06

Locations

US (1)