Combining Donepezil With Perceptual Learning in Normal and Amblyopic Human The Effect of Donepezil on Perceptual Learning in Adult Amblyopia

The Effect of Donepezil on Perceptual Learning in Adult Amblyopia

The research deals with amblyopia or lazy eye, a condition that affects about 3% of the population, and results in a variety of visual deficits. Recent work suggests that there is limited neural plasticity in the visual system of adults with amblyopia. This study is aimed at understanding and increasing this plasticity. In this study, the investigators aim to understand how the amblyopic brain learns and how this process is affected by a drug called donepezil, which is sometimes given as a treatment for Alzheimer's disease. The investigators hope that this study will help to identify the chemical components that help the brain to learn, as well as the mechanism of amblyopia. The investigators also plan to test the normal periphery, as control.

Study Overview

• Status: Completed
• Conditions: Amblyopia
• Intervention / Treatment: Drug: Donepezil; Behavioral: Single-letter training; Behavioral: Uncrowd training

Detailed Description

The research deals with amblyopia or lazy eye, a condition that affects about 3% of the population, and results in a variety of visual deficits. Recent work suggests that there is limited neural plasticity in the visual system of adults with amblyopia. This study is aimed at understanding and increasing this plasticity. In this study, the investigators aim to understand how the amblyopic brain learns and how this process is affected by a drug called donepezil, which is sometimes given as a treatment for Alzheimer's disease. The investigators hope that this study will help to identify the chemical components that help the brain to learn, as well as the mechanism of amblyopia. The investigators also plan to test the normal periphery, as control.

In this study, donepezil will be administered while amblyopic subjects (or normally sighted subjects tested in the periphery) are trained on a low-contrast single-letter recognition task, or an uncrowd task (recognizing a letter closely embedded within two other letters). Subjects will be asked to identify the target letter (the low-contrast single letter, or the letter embedded within other letters). Training will take place for 10 consecutive days. Pre- and post-tests will be conducted immediately before and after training, and will consist of the measurements of visual acuity, crowding extent and contrast threshold for recognizing single letters.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Berkeley, California, United States, 94720
      • University of California, Berkeley

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Subjects with amblyopia

Inclusion Criteria:

• corrected visual acuity being 20/30 or worse in the poorer eye (at least 20/20 in the better eye)
• reduced stereoacuity
• normal retina

Exclusion Criteria:

• with other diagnosed eye diseases

Subjects with normal vision

Inclusion Criteria:

• corrected visual acuity at least 20/20 in each eye
• normal stereoacuity
• normal retina

Exclusion Criteria:

• with other diagnosed eye diseases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Single-letter training group; Subjects will be trained on a low-contrast single-letter task. The task is to identify a faint letter (low-contrast). Performance will be measured as correct or incorrect. Training will consist of identifying these low-contrast letters for 1000 trials per day (10 blocks of 100 trials each, subjects can take breaks in-between blocks), for a total of 10 days. During training, subjects will be administered a daily dosage of 5 mg of donepezil. Immediately before and after training (the day before and the day after), subjects' performance on (1) visual acuity; (2) contrast for identifying letters and (3) crowding extent will be measured.	Drug: Donepezil; Donepezil will be administered to subjects three days before each training, and during training, to evaluate if donepezil improves the effectiveness of training.; Other Names: Aricept; Behavioral: Single-letter training; Subjects will undergo training to identify single letters (10,000 trials, or 10 blocks per session for 10 sessions).
Active Comparator: Uncrowd training group; Subjects will be trained on an uncrowd task (identifying the middle letter of groups of three letters presented). Performance will be measured as correct or incorrect. Training will consist of identifying these letters for 1000 trials per day (10 blocks of 100 trials each, subjects can take breaks in-between blocks), for a total of 10 days. During training, subjects will be administered a daily dosage of 5 mg of donepezil. Immediately before and after training (the day before and the day after), subjects' performance on (1) visual acuity; (2) contrast for identifying letters and (3) crowding extent will be measured.	Drug: Donepezil; Donepezil will be administered to subjects three days before each training, and during training, to evaluate if donepezil improves the effectiveness of training.; Other Names: Aricept; Behavioral: Uncrowd training; Subjects will undergo training to identify letters closely flanked by other letters (10,000 trials, or 10 blocks per session for 10 sessions).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in percent-correct performance in the respective training task	During training, for each trial, participants' responses can be categorized as correct or incorrect. The investigators will use the percent-correct performance to quantify the performance in each block, and this percent-correct performance will be measured throughout training (i.e. for each block on each day (10 blocks per day), and for 10 training days).	During training (performance will be summarized for each block of trials (a block takes approximately 5 - 10 min to complete). In other words, there should be 100 points of measurements throughout the training period.)
Visual acuity (the smallest letter the participants can see)	The change in visual acuity before and after (one day before and one day after) training will be compared. The change will be expressed as a ratio.	Immediately (one day) before and after training
Contrast sensitivity for identifying single letters (the lowest contrast required to identify letters)	Contrast refers to the smallest difference in luminance between a letter and its background. This is a standard clinical measurement. Essentially, the lowest contrast letter is also the faintest letter that a participant can see. The change in contrast sensitivity for identifying single letters before and after (one day before and one day after) training will be compared. The change will be expressed as a ratio.	Immediately (one day) before and after training
Crowding extent (the extent over which adjacent letters will affect the recognition of a letter)	Crowding extent refers to the minimum distance between adjacent letters such that the presence of adjacent letters affects the recognition of a target letter. Usually the letter separation will be adjusted until the adjacent letters no longer affects how well the middle letter can be recognized. This distance is the crowding extent. The change in the crowding extent before and after (one day before and one day after) training will be measured. The change will be expressed as a ratio.	Immediately (one day) before and after training

Collaborators and Investigators

• Sponsor: Dennis Levi
• Investigators: Principal Investigator: Dennis M Levi, OD, PhD, University of California, Berkeley

Publications and helpful links

General Publications

• Chung STL, Li RW, Silver MA, Levi DM. Donepezil Does Not Enhance Perceptual Learning in Adults with Amblyopia: A Pilot Study. Front Neurosci. 2017 Aug 7;11:448. doi: 10.3389/fnins.2017.00448. eCollection 2017.

Helpful Links

• Article in Frontiers in Neuroscience

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2012
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: March 23, 2017
• First Submitted That Met QC Criteria: April 5, 2017
• First Posted (Actual): April 12, 2017

Study Record Updates

• Last Update Posted (Actual): January 17, 2019
• Last Update Submitted That Met QC Criteria: January 15, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: visual acuity; amblyopia; donepezil; contrast sensitivity; perceptual learning; crowding
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Sensation Disorders; Vision Disorders; Amblyopia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Nootropic Agents; Cholinesterase Inhibitors; Donepezil
• Other Study ID Numbers: 020976_01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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.: Yes