Olfactory Deficits in MCI as Predictor of Improved Cognition on Donepezil

NCT ID: NCT01845636

Last Updated: 2018-07-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2016-03-31

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.

Detailed Description

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.

Conditions

Mild Cognitive Impairment

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Donepezil

Intervention Type: 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.

Atropine

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

Aricept; Atropine sulfate ophthalmic solution 1%

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• Clinical stroke with residual neurological deficits. MRI findings of cerebrovascular disease (small infarcts, lacunes, periventricular disease) in the absence of clinical stroke with residual neurological deficits will not lead to exclusion.
• Patients receiving cholinesterase inhibitors (donepezil, rivastigmine, galantamine) or memantine will be excluded.
• Acute, severe, unstable medical illness. For cancer, patients with active illness or metastases will be excluded, but past history of successfully treated cancer will not lead to exclusion.
• 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.
• Exclusion criterion for olfaction: history of anosmia due to any cause (e.g. traumatic or congenital) verified by UPSIT score of <11 out of 40; head trauma with loss of consciousness; nasal sinus disease, current upper respiratory infection; severe allergies to odors; current smoker > 1 pack daily.

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 95 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

United States Department of Defense

FED

Sponsor Role: collaborator

New York State Psychiatric Institute

OTHER

Sponsor Role: lead

Responsible Party

Davangere P. Devanand

Professor of Clinical Psychiatry and Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Davangere Devanand, M.D.

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Gregory Pelton, M.D.

Role: STUDY_DIRECTOR

Columbia University

Locations

New York State Psychiatric Institute

New York, New York, United States

Countries

United States

Other Identifiers

W81XWH-12-0142

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

6577

Identifier Type: -

Identifier Source: org_study_id