Factors in Learning And Plasticity: Macular Degeneration (FLAP)

February 4, 2026 updated by: Kristina M Visscher, University of Alabama at Birmingham

Characterization of Multiple Factors in Training and Plasticity in Central Vision Loss: Macular Degeneration

A greater understanding of plasticity after central vision loss can inform new therapies for treating low vision and has the potential to benefit millions of individuals suffering from low vision. The treatment of low vision is particularly relevant to the mission of the NEI to support research on visual disorders, mechanisms of visual function, and preservation of sight. The comparison of different training and outcome factors is in line with the NIMH RDOC framework and studies in an aging population are consistent with the mission of the NIA.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Research on perceptual learning (PL) has been dominated by studies that seek to isolate and improve individual visual processes. However, an important translational outcome of PL research is to address the needs of patients with vision loss, who seek to improve performance on daily tasks such as reading, navigation, and face recognition. These more ecological cases of behavioral change and cortical plasticity, which are inherently complex and integrative, have revealed significant gaps in a more holistic understanding of how multiple visual processes and their associated brain systems jointly contribute to durable and generalizable PL. To address these gaps, here the investigators study simulated and natural central vision loss. The investigators focus on macular degeneration (MD), one of the most common causes of vision loss (projected to affect 248 million people worldwide by 2040), which results from damage to photoreceptors in the macula that disrupts central vision. Such central vision loss is a superb lens through which study to how ecologically relevant changes in the use of vision relate to changing brain activity and connectivity because it represents a massive alteration in visual experience requiring reliance on peripheral vision for daily tasks. With the use of eye-trackers and gaze-contingent displays that induce central scotomas, central vision loss can be simulated in normally seeing individuals, who then develop peripheral looking patterns that resemble compensatory vision strategies seen in MD patients. Ideal use of peripheral vision requires improvement in multiple vision domains, three of the most important being: early visual processing (e.g., visual sensitivity), mid-level visual processing (e.g., spatial integration), and attention and eye-movements. To date, no study has systematically investigated these three domains of PL and their neural underpinnings. The proposed research plan rests on rigorous prior work showing that PL influences multiple brain structures and functions related to these three domains. The investigators propose a novel approach of systematically measuring how different training regimes related to the three domains influence a broad range of psychophysical and ecological behaviors (Aim 1), how these changes arise from plasticity in brain structure and function (Aim 2), and how PL after simulated central vision loss compares to PL in MD (Aim 3). This work is significant and innovative as it will be the first integrated study of PL characterizing multiple trainable factors and their impact on diverse behavioral outcomes and on cutting-edge assessments of neural representations and dynamics. It is also the first study to directly compare PL in MD patients with PL in a controlled model system of central visual field loss with simulated scotomas, which if validated will allow the use of this model system to interrogate MD in larger samples of healthy individuals. The investigators will also share a unique dataset that will help the field to understand behavioral and neural plasticity after central vision loss and individual differences in responsiveness to training. Finally, this work will illuminate basic mechanisms of brain plasticity after sensory loss that may generalize to other forms of rehabilitation after peripheral or central damage.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Rachel A Chua, MS
  • Phone Number: 205-410-4041
  • Email: r2chel@uab.edu

Study Contact Backup

  • Name: Kristina M Visscher, PhD
  • Phone Number: 205-934-0497
  • Email: kmv@uab.edu

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Recruiting
        • UAB
        • Contact:
        • Contact:
          • Kristina M Visscher, PhD
          • Phone Number: 205-934-0497
          • Email: kmv@uab.edu
        • Principal Investigator:
          • Kristina M Visscher, Ph.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 89 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Aged 18-89
  • Severely impaired vision in both eyes (20/100 or worse)
  • diagnosis of Macular Degeneration by an Ophthalmologist
  • Light sensitivity in the macular retina that is at least 10 dB units worse than in peripheral regions, as demonstrated by a scanning laser ophthalmoscope (MAIA)
  • Medical record review indicating this level of disease severity has been present for at least 2 years
  • Reside within 50 miles of study site

Exclusion Criteria:

  • Pacemaker or any ferromagnetic metal implanted in their body
  • Metal of any type implanted in their head (limited dental work is acceptable)
  • Claustrophobia
  • Being hearing-impaired
  • Weight over 300 pounds
  • Maximum body girth over 60 inches
  • Previous serious head injury
  • Presence of hallucinations or delusions
  • Excessive old, or colorful tattoos, especially near the head
  • Pregnancy
  • Braces/permanent retainer

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Training visual sensitivity
A standard Perceptual Learning approach to train early visual processes of discriminating the orientation of Gabor patches presented at threshold- level contrast. Preliminary data, using this method, in normally seeing and MD participants show both feasibility and preliminary evidence that this training gives rise to improvements in acuity.
Behavioral: Training visual sensitivity
Investigators adopt a standard PL approach to train early visual processes of discriminating the orientation of Gabor patches presented at threshold contrast. Across training blocks, Gabors will range in spatial frequency, where contrast is adapted with a 3/1 staircase. Whenever a specific contrast threshold is reached, spatial frequency will increase by 2 cycles per degree and contrast will be reset. Preliminary data from this method in normally seeing and MD participants show both feasibility and tentative evidence that this training gives rise to improvements in acuity.
Experimental: Combination training
In combination training, investigators test the extent to which a combined training gives rise to the joint benefits of each training individually, or integrative benefits potentially surpassing benefits of the individual training alone. The visual sensitivity task will alternate across blocks with the spatial integration task, using the timing of targets and location switches from spatial attention training.
Behavioral: Combination training
Daily tasks involve a combination of being sensitive to basic visual features, being able to integrate these features, and directing attention and eye movements to better evaluate the information of potential interest. To address this integrative nature of real-world vision, this condition combines elements of training visual sensitivity, spatial integration, and spatial attention.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change from Baseline Radial Bias from the Crowding Task after completion of Training at approximately 7 weeks
Time Frame: Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
The ratio of the crowding threshold along the axis connected to the fovea vs. along the orthogonal axis.
Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Change from Baseline Saccadic Precision after Completion of Training at approximately 7 weeks
Time Frame: Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Consistency across trials in placement of the first saccade calculated by the distribution across trials (bivariate contour ellipse area) of the landing point of the first fixation of each trial.
Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Change from Baseline Fixation Stability after Completion of Training at approximately 7 weeks
Time Frame: Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Normalizing fixations in the PRL to the first fixation to that region and calculating the distribution of all fixation locations in this normalized space (measured as a bivariate contour ellipse area).
Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change from Baseline Acuity after Completion of Training at approximately 7 weeks
Time Frame: Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Acuity threshold from the Landolt C task.
Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Change from Baseline Contrast Sensitivity after Completion of Training at approximately 7 weeks
Time Frame: Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Threshold value from contrast sensitivity task.
Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Change from Baseline Minimal print size from the MNREAD task after Completion of Training at approximately 7 weeks
Time Frame: Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Minimal print size from the MNREAD task
Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Change from Baseline Precision of Reconstructed Representation of Stimulus Orientation after Completion of Training at approximately 7 weeks
Time Frame: Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Precision of reconstructed representation of stimulus orientation (quantified with FWHM)
Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Change from Baseline Population receptive field size in V1, V2 and V3 representations of URL and PRL after Completion of Training at approximately 7 weeks
Time Frame: Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Population receptive field size in V1, V2 and V3 representations of URL and PRL (quantified as PRF sigma in the swath of cortex associated with that retinal location).
Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Change from Baseline Cortical thickness in V1, V2 and V3 representations of the PRL and URL after Completion of Training at approximately 7 weeks
Time Frame: Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Cortical thickness in V1, V2 and V3 representations of the PRL and URL (quantified as mm of cortical thickness)
Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Change from Baseline Orientation jitter threshold in the contour integration task at PRL or URL after Completion of Training at approximately 7 weeks
Time Frame: Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Orientation jitter threshold in the contour integration task (quantified as threshold average jitter) at PRL or URL.
Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Change from Baseline Crowding Threshold after Completion of Training at approximately 7 weeks
Time Frame: Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
In the contour integration task stimuli are untrained contours of alphanumeric characters made of Gabor elements. This test allows us to estimate how the magnitude of crowding may change at the PRL compared to the non-PRL.
Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Change from Baseline Decoding classification accuracy for an attended character after Completion of Training at approximately 7 weeks
Time Frame: Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Decoding classification accuracy for an attended character, based on decoding from MRI data within VWFA and LOC regions of interest.
Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Change from Baseline Strength of background connectivity between areas with larger receptive fields (V4) to the smaller receptive fields contributing information to that area. after Completion of Training at approximately 7 weeks
Time Frame: Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
This is measured as functional connectivity (z-transformed Pearson's r) between voxels in V1 to voxels in V4 in that represent the same portion of retinotopically mapped space. Measured in portions of cortex representing PRL and URL.
Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Change from Baseline Sustained Attention after Completion of Training at approximately 7 weeks
Time Frame: Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Reaction time of detection of orientation of Landolt Cs presented in an RSVP stream at the beginning of each trial.
Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Change from Baseline Endogenous Attention after Completion of Training at approximately 7 weeks
Time Frame: Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Endogenous attention: reaction time when switching between locations due to an endogenous cue on valid vs nonvalid trials.
Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Change from Baseline Exogenous Attention after Completion of Training at approximately 7 weeks
Time Frame: Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Exogenous attention: reaction time when switching between locations due to an exogenous cue on valid vs. nonvalid trials.
Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Change from Baseline Saccadic Re-referencing after Completion of Training at approximately 7 weeks
Time Frame: Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Saccadic Re-referencing: number of first fixations that do not cover the target location with the scotoma.
Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Change from Baseline Decoding classification accuracy for decoding the locus of spatial attention (PRL or URL), regardless of stimulus type after Completion of Training at approximately 7 weeks
Time Frame: Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Decoding classification accuracy for decoding the locus of spatial attention (PRL or URL), regardless of stimulus type. This will be examined in frontal (FEF), parietal (SPL/IPS) and higher order visual (LOC) regions.
Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Change from Baseline Top-down modulation of visual areas after Completion of Training at approximately 7 weeks
Time Frame: Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Top-down modulation of visual areas: background connectivity between frontoparietal control regions (FEF, SPL/IPS) and visual areas ( V1, V2, V3).
Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Change from Baseline Reading speed in the MNREAD task after Completion of Training at approximately 7 weeks
Time Frame: Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Reading speed in the MNREAD task (words per minute).
Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Change from Baseline Completion time in the trail making task after Completion of Training at approximately 7 weeks
Time Frame: Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average
Completion time in the trail making task
Baseline and Within 3 weeks of training completion, training is complete 7 weeks from baseline on average

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Alabama at Birmingham

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of California, Riverside

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 5, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 7, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 12, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 9, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 4, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 300006197 (Study 2)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Results of the project will be submitted to the relevant repository (ClinicalTrials.gov, or Open-ScienceFramework, MRI data to OpenfMRI) within one year of the final participant completing data collection. The investigators expect to report participant flow by group (intervention or control), participant demographics (age, sex assigned at birth, years of education), outcome measures and statistical analyses, adverse events (if applicable), and limitations or caveats of our results. The investigators also will ensure that the final protocol and statistical analysis code are uploaded to the record. No Protected Health Information will be shared.

IPD Sharing Time Frame

Within one year of the final participant completing data collection.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF
  • ANALYTIC_CODE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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