Trial record 4 of 4 for:    Open Studies | "Olfaction Disorders"

Olfactory Deficits and Donepezil Treatment in Cognitively Impaired Elderly

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by New York State Psychiatric Institute
Sponsor:
Collaborators:
Information provided by (Responsible Party):
New York State Psychiatric Institute
ClinicalTrials.gov Identifier:
NCT01951118
First received: September 18, 2013
Last updated: August 14, 2014
Last verified: August 2014
  Purpose

Olfactory identification deficits occur in patients with Alzheimer's disease (AD), are associated with disease severity, predict conversion from mild cognitive impairment (MCI) to AD and are associated with healthy elderly subjects developing MCI. Odor (olfactory) identification deficits may reflect degeneration of cholinergic inputs to the olfactory bulb and other olfactory brain regions. Acetylcholinesterase inhibitors (ACheI) like donepezil show modest effects in improving cognition but can be associated with adverse effects and increased burden and costs because of the need for prolonged, often lifelong, treatment. Converging findings on odor identification test performance (UPSIT, scratch and sniff 40-item test) from four pilot studies, including two of our own, suggest that acute change in the UPSIT in response to an anticholinergic challenge (atropine nasal spray), incremental change over 8 weeks, and even the baseline UPSIT score by itself, may predict cognitive improvement with ACheI treatment in MCI and AD. If change in odor identification deficits can help to identify which patients should receive ACheI treatment, this simple inexpensive approach will advance the goal of improving personalized treatment, improve selection and monitoring of patients for ACheI treatment, reduce needless ACheI exposure with risk of side effects, and decrease health care costs.


Condition Intervention Phase
Alzheimer Disease
Mild Cognitive Impairment
Delirium, Dementia, Amnestic, Cognitive Disorders
Drug: Donepezil
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Olfactory Deficits and Donepezil Treatment in Cognitively Impaired Elderly

Resource links provided by NLM:


Further study details as provided by New York State Psychiatric Institute:

Primary Outcome Measures:
  • Change over time in Selective Reminding Test (SRT) Scores [ 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.


Secondary Outcome Measures:
  • 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.

  • Clinician's Interview Based Impression (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 in AD and MCI trials.

  • 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.


Other Outcome Measures:
  • 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.


Estimated Enrollment: 170
Study Start Date: October 2013
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: 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. 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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   55 Years to 95 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Study 1

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-III 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
  • Retains capacity to consent

Exclusion Criteria:

  • 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 less than or equal to 2 mg daily and narcotics will also not be permitted.
  • Meets criteria for dementia by Diagnostic and Statistical Manual IV (DSM-IV) or probable Alzheimer's disease by National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA)
  • Meets Diagnostic and Statistical Manual IV Text Revision (DSM IV TR) 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
  • Cystic Fibrosis
  • 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. Patients already receiving one of these medications at screening who undergo a 2-week washout before starting all study procedures will not 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.
  • 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.
  • Exclusion criteria for atropine nasal spray: presence of nasal deformity or disease that makes it difficult to administer the nasal spray reliably. A patient who cannot complete the atropine nasal spray procedure can still participate in the rest of the study.

Study 2

Inclusion Criteria:

  • Of either sex, age 55-95 years old
  • Diagnosis of probable Alzheimer's disease (NINCDS-ADRDA criteria) and the diagnosis of "Probable AD dementia: core clinical diagnosis with amnestic or nonamnestic initial presentation".
  • Folstein Mini Mental State (MMSE) score 18-27 out of 30
  • Availability of informant
  • Retains capacity to consent

Exclusion Criteria:

  • 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 less than or equal to 2 mg daily and narcotics will also not be permitted.
  • Meets DSM IV TR 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
  • Cystic Fibrosis
  • 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. Patients already receiving one of these medications at screening who undergo a 2-week washout before starting all study procedures will not 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.
  • 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.
  • Exclusion criteria for atropine nasal spray: presence of nasal deformity or disease that makes it difficult to administer the nasal spray reliably. A patient who cannot complete the atropine nasal spray procedure can still participate in the rest of the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01951118

Locations
United States, New York
New York State Psychiatric Institute Recruiting
New York, New York, United States, 10032
Contact: Jennifer Ferrar, B.S.    646-774-7204    ferrarj@nyspi.columbia.edu   
Contact: Daniel Valmas, B.A.    646-774-7202    dv2329@columbia.edu   
Principal Investigator: Davangere Devanand, M.D.         
Sub-Investigator: Gregory Pelton, M.D.         
Sub-Investigator: Edward Huey, M.D.         
Sub-Investigator: Karen Bell, M.D.         
Sponsors and Collaborators
New York State Psychiatric Institute
Investigators
Principal Investigator: Davangere Devanand, M.D. Columbia University
  More Information

No publications provided

Responsible Party: New York State Psychiatric Institute
ClinicalTrials.gov Identifier: NCT01951118     History of Changes
Other Study ID Numbers: 6655, 1R01AG041795
Study First Received: September 18, 2013
Last Updated: August 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by New York State Psychiatric Institute:
Smell
Olfaction Disorders
Atropine
Donepezil
Cholinesterase Inhibitors
Cognition Disorders

Additional relevant MeSH terms:
Alzheimer Disease
Cognition Disorders
Delirium
Dementia
Delirium, Dementia, Amnestic, Cognitive Disorders
Mild Cognitive Impairment
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Mental Disorders
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms
Cholinesterase Inhibitors
Donepezil
Atropine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Adjuvants, Anesthesia
Central Nervous System Agents
Therapeutic Uses
Anti-Arrhythmia Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on September 14, 2014