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Detecting an Early Response to Donepezil With Measures of Visual Attention

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ClinicalTrials.gov Identifier: NCT03073876
Recruitment Status : Active, not recruiting
First Posted : March 8, 2017
Last Update Posted : January 11, 2019
Sponsor:
Collaborator:
Queens College, The City University of New York
Information provided by (Responsible Party):
NYU Langone Health

Brief Summary:

Acetylcholinesterase inhibitors (AChE-I) comprise a class of drugs used to treat Alzheimer's disease (AD), but controversy about their usefulness remains. Modest response rates of treated versus placebo groups, small effect sizes with respect to efficacy, drug costs, and clinical relevance of the effects are problematic. Standard efficacy measures of efficacy are not sufficiently sensitive, and trying to assess cognitive change after 4-6 months of therapy confounds the drug effect and the natural progression of the disease.

Surprisingly, attention has never been included in the assessment of AChE-I drugs. The rationale for using attentional measures are that (1) Attentional deficits are recognized as a critical cognitive change in the earliest phases of AD; (2) Attentional function is directly mediated by the cholinergic system, and responds rapidly to cholinergic augmentation, particularly on tasks that tax available attentional capacity are dose dependent; and (3) Acetylcholine is depleted in AD. However, the link between attention and cholinergic depletion in AD has not been fully explored, especially with regard to response to cholinergic treatment.

The study tests if attentional performance can be a more sensitive marker of response. In a longitudinal study we measure attentional, as well as cognitive and behavioral performance in de novo AD patients undergoing donepezil treatment. The investigators develop visual attentional measures and contrast them to global and domain-specific cognitive scores on three occasions (T1) baseline pre-treatment, (T2) after approximately 6 weeks, and (T3) after 6 months treatment. The T1-to-T2 arm is a double-blind placebo control period, after which members of the placebo group start open-label treatment. The assessment at 6 months allows us to determine whether the changes seen earlier at T2 can predict patients who respond, or determine which measures best predict response.

We hypothesize that attention measures are more sensitive than standard global measures or other cognitive domains and that the change of attentional function can be detected after only after approximately 6 weeks treatment.

Knowledge from this project will facilitate and inform our decisions about individual patients undergoing pharmacological treatment.


Condition or disease Intervention/treatment Phase
Alzheimer Disease Drug: Donepezil Hydrochloride Drug: Placebo Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double Blind Placebo Control
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Study drug was prepared by research pharmacist who was the only person privy to group assignment. Drug and Placebo pills looked identical.
Primary Purpose: Other
Official Title: Detecting an Early Response to Donepezil With Measures of Visual Attention
Actual Study Start Date : December 1, 2005
Actual Primary Completion Date : October 8, 2009
Estimated Study Completion Date : July 31, 2019


Arm Intervention/treatment
Experimental: Drug
Participants in the Drug group received oral 5mg of Donepezil Hydrochloride daily for 6 months. The Drug group was assessed at baseline, after approximately 6 weeks and after 6 months of treatment. The baseline to 6 weeks phase was part of the double-blind, placebo controlled portion of the trial.
Drug: Donepezil Hydrochloride
5mg of Donepezil Hydrochloride by mouth
Other Name: Aricept

Placebo Comparator: Placebo

Participants in the placebo group first received oral administration of a placebo pill for approximately 6 weeks. After that initial interval, the study was unblinded and participants in the placebo group then received 5mg of donepezil hydrochloride treatment for 6 months.

The Placebo group was evaluated at baseline, after 6 weeks of placebo, after 6 weeks of donepezil hydrochloride drug treatment, and 6 months of donepezil hydrochloride treatment.

Drug: Donepezil Hydrochloride
5mg of Donepezil Hydrochloride by mouth
Other Name: Aricept

Drug: Placebo
prepared placebo looking exactly the same as drug. Participants took placebo by mouth for approximately 6 weeks, and after unblinding, they took donepezil hydrochloride for 6 months.
Other Name: Placebo pill




Primary Outcome Measures :
  1. Change in Foreperiod Effect task from baseline to 6 weeks [ Time Frame: Baseline to 6 weeks ]
    Computerized attention task measures response time to detect a target presented at varied interstimulus intervals.

  2. Change in Attentional Blink task from baseline to 6 weeks [ Time Frame: Baseline to 6 weeks ]
    Computerized attention task measures the accuracy of reporting stimuli that are presented at varied time intervals.

  3. Change in Corert Orienting task from baseline to 6 weeks [ Time Frame: Baseline to 6 weeks ]
    Computerized attention task measuring response time to detect a target after an spatial orienting cue (valid, invalid, neutral).

  4. Change of Foreperiod Effect task from baseline to 6 months [ Time Frame: Baseline to 6 months ]
    Computerized attention task measures response time to detect a target presented at varied interstimulus intervals.

  5. Change in Attentional Blink task from baseline to 6 months [ Time Frame: Baseline to 6 months ]
    Computerized attention task measures the accuracy of reporting stimuli that are presented at varied time intervals.

  6. Change of Covert Orienting task from baseline to 6 months [ Time Frame: Baseline to 6 months ]
    Computerized attention task measuring response time to detect a target after an spatial orienting cue (valid, invalid, neutral).


Secondary Outcome Measures :
  1. Change in Dementia Rating Scale [ Time Frame: Baseline to 6 weeks and to 6 months ]
    Global measure of cognitive function

  2. Change in Mini Mental Status Examination [ Time Frame: Baseline to 6 weeks and to 6 months ]
    Global measure of cognitive function

  3. Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale [ Time Frame: Baseline to 6 weeks and to 6 months ]
    Global measure of cognitive function

  4. Change in Clinical Dementia Rating [ Time Frame: Baseline to 6 weeks and to 6 months ]
    Global measure of cognitive function

  5. Change in Digit Span [ Time Frame: Baseline to 6 weeks and to 6 months ]
    Measure of attention function

  6. Change in Hopkins Verbal Learning Test- Revised [ Time Frame: Baseline to 6 weeks and to 6 months ]
    Measure of memory function

  7. Change in Language function assessed with the Letter and Category Fluency Test [ Time Frame: Baseline to 6 weeks and to 6 months ]
    Measure of language function

  8. Change in Executive function assessed with the Trail Making Test [ Time Frame: Baseline, 6 weeks and 6 months ]
    Measure of executive function

  9. Change in Visuospatial function assessed with Visual Form Discrimination [ Time Frame: Baseline to 6 weeks and to 6 months ]
    Measure of visuospatial function



Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years to 95 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Clinical diagnosis of Alzheimer's Disease
  • Mini Mental State Examination score >15 / 30
  • Can swallow pills

Exclusion Criteria:

  • No other dementia due to Parkinson's disease, Lewy Body dementia, Normal Pressure Hydrocephalus, Fronto-temporal dementia, or prominent cerebral vascular accident
  • No prior or concurrent use of cholinesterase inhibitors
  • No prior or concurrent use of memantine hydrochloride
  • No other concurrent anticholinergic treatments

Information from the National Library of Medicine

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): NCT03073876


Locations
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United States, New York
Winthrop-University Hospital
Mineola, New York, United States, 11501
Sponsors and Collaborators
NYU Langone Health
Queens College, The City University of New York
Investigators
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Principal Investigator: Nancy Foldi, PhD NYU Winthrop Hospital

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: NYU Langone Health
ClinicalTrials.gov Identifier: NCT03073876     History of Changes
Other Study ID Numbers: WUH 05030
First Posted: March 8, 2017    Key Record Dates
Last Update Posted: January 11, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by NYU Langone Health:
Alzheimer Disease
Attention
Donepezil hydrochloride
Additional relevant MeSH terms:
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Donepezil
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Nootropic Agents