Visual Rehabilitation After Occipital Stroke

• ClinicalTrials.gov Identifier: NCT04798924
• Recruitment Status: Recruiting
• First Posted: March 15, 2021
• Last Update Posted: January 10, 2024
• Sponsor: University of Rochester
• Collaborator: National Institutes of Health (NIH)
• Information provided by (Responsible Party): Krystel Huxlin, University of Rochester

Tracking Information

• First Submitted Date: February 25, 2021
• First Posted Date: March 15, 2021
• Last Update Posted Date: January 10, 2024
• Actual Study Start Date: July 19, 2021
• Estimated Primary Completion Date: June 1, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 14, 2021)

Direction Discrimination Threshold [ Time Frame: baseline, 6 months, 12 months ]

For each subject, we will measure the ability to detect differences in the motion direction of visual stimuli relative to horizontal, measured in degrees of visual angle. These assessments will be based on what can be reliably detected at a 72-75% correct level of performance. These measures of change will be evaluated baseline to 6-months post-stroke, then 6- to 12-months post stroke, and baseline to 12-months.** **NOTE: Our protocol allows for a +1 month variance for all timepoints.

Original Primary Outcome Measures (submitted: March 12, 2021)

Direction Discrimination Threshold [ Time Frame: baseline, 6 months, 12 months ]

For each subject, we will measure the ability to detect changes in the motion direction of visual stimuli, measured by degree of visual angle. These assessments will be based on what motion can be reliably detected at a 75% correct level of performance. These measures of change will be evaluated baseline to 6-months post-stroke, then 6- to 12-months post stroke, and baseline to 12-months.

Current Secondary Outcome Measures (submitted: October 14, 2021)

• Direction Integration Threshold [ Time Frame: baseline, 6 months, 12 months ]
  This will measure the ability of subjects to integrate across a range of motion directions measured in degrees of visual angle. These assessments will be based on what range of motion directions can be reliably integrated at a 72-75% correct level of performance. These measures of change will be evaluated baseline to 6-months post-stroke, then 6- to 12-months post stroke, and baseline to 12-months. **NOTE: Our protocol allows for a +1 month variance for all timepoints.
• Contrast Sensitivity for Direction [ Time Frame: baseline, 6 months, 12 months ]
  Assessment of visual perception transfer to untrained psychophysical tasks of contrast sensitivity for direction discrimination. For each subject, we will measure the ability to correctly detect the motion direction of visual stimuli that are also varying in contrast against a grey background. We will measure the luminance contrast that can be reliably detected at a 72-75% correct level of performance. These measures of change will be evaluated baseline to 6-months post-stroke, then 6- to 12-months post stroke, and baseline to 12-months. **NOTE: Our protocol allows for a +1 month variance for all timepoints.
• contrast sensitivity for static orientation [ Time Frame: baseline, 6 months, 12 months ]
  Assessment of visual perception transfer to untrained psychophysical tasks of contrast sensitivity for static orientation discrimination. For each subject, we will measure the ability to correctly detect the orientation of non-moving visual stimuli that vary in contrast against a grey background. We will measure the luminance that can be reliably detected at a 72-75% correct level of performance. These measures of change will be evaluated baseline to 6-months post-stroke, then 6- to 12-months post stroke, and baseline to 12-months. **NOTE: Our protocol allows for a +1 month variance for all timepoints.
• Ganglion cell complex thickness laterality [ Time Frame: baseline, 6 months, 12 months ]
  Change in thickness of the ganglion cell complex will be measured by retinal optical coherence tomography (OCT) scans from baseline to 6- and 12- months post stroke.** We will perform OCT imaging of the foveal region of the retina (6mm ETDRS) in both eyes of each patient. Images will be automatically segmented. Estimated thickness of the ganglion cell complex will be extracted and aligned with estimates of the blind field's visual sensitivity obtained from fundus-controlled MAIA perimetry. We will then compute a laterality index LI as follows: LIGCCT=(Tc-Ti)/(Tc+Ti) where Tc=thickness in the control lateral OCT quadrant, Ti=thickness in the impaired lateral OCT quadrant. **NOTE: Our protocol allows for a +1 month variance for all timepoints.
• Ganglion cell complex volume laterality [ Time Frame: baseline, 6 months, 12 months ]
  Change in volume of the ganglion cell complex will be measured by retinal optical coherence tomography (OCT) scans from baseline to 6- and 12- months post stroke.** We will perform OCT imaging of the foveal region of the retina (6mm ETDRS) in both eyes of each patient. Images will be automatically segmented. Estimated volume of the ganglion cell complex will be extracted and aligned with estimates of the blind field's visual sensitivity obtained from fundus-controlled MAIA perimetry. We will then compute a laterality index as follows: LIGCCT=(Tc-Ti)/(Tc+Ti) where Tc=thickness in the control lateral OCT quadrant, Ti=thickness in the impaired lateral OCT quadrant. **NOTE: Our protocol allows for a +1 month variance for all timepoints.
• Optic Tract (OT) laterality [ Time Frame: baseline, 6 months, 12 months ]
  OT volume analysis will be performed from high resolution structural T1 MRI images of the brain. Mirrored masks of equal size will be hand-drawn over the OTs in each brain slice of a given subject, starting three slices posterior to the optic chiasm and continuing posteriorly until the OTs are no longer distinct from surrounding structures. The volume of each optic tract will be calculated from these masks by first establishing the maximum voxel intensity (range from 0 to 255) across the two OTs, then counting the number of voxels in each OT mask with brightness values between 5 and 85% of this maximum. We will then compute an OT laterality Index (LI85) to represent the relative difference in estimated volume between the two OTs of each participant, where LI85=(OTc-OTi)/(OTc+OTi), where OTc=number of voxels with brightness 5-85% of maximum in the contralesional OT and OTi = number of voxels with brightness 5-85% of maximum in the ipsilesional OT.

Original Secondary Outcome Measures (submitted: March 12, 2021)

• Direction Integration Threshold [ Time Frame: baseline, 6 months, 12 months ]
  This will measure the ability of subjects to transfer visual perception abilities to untrained locations within their visual field. For each subject, we will measure the ability to detect changes in the motion direction of visual stimuli, measured by degree of visual angle. These assessments will be based on what motion can be reliably detected at a 75% correct level of performance. These measures of change will be evaluated baseline to 6-months post-stroke, then 6- to 12-months post stroke, and baseline to 12-months.
• Contrast Sensitivity for Direction [ Time Frame: baseline, 6 months, 12 months ]
  Assessment of visual perception transfer to untrained psychophysical tasks of contrast sensitivity for direction. For each subject, we will measure the ability to detect changes in the motion direction of visual stimuli that are also varying in contrast against a grey background. We will measure the degree of luminance that can be reliably detected at a 75% correct level of performance. These measures of change will be evaluated baseline to 6-months post-stroke, then 6- to 12-months post stroke, and baseline to 12-months.
• contrast sensitivity for static orientation [ Time Frame: baseline, 6 months, 12 months ]
  Assessment of visual perception transfer to untrained psychophysical tasks of contrast sensitivity for static orientation. For each subject, we will measure the ability to detect changes in the orientation of non-moving visual stimuli that vary in contrast against a grey background. We will measure the degree of luminance that can be reliably detected at a 75% correct level of performance. These measures of change will be evaluated baseline to 6-months post-stroke, then 6- to 12-months post stroke, and baseline to 12-months.
• Ganglion cell complex thickness laterality [ Time Frame: baseline, 6 months, 12 months ]
  Change in thickness of the ganglion cell complex will be measured by retinal optical coherence tomography (OCT) scans from baseline to 6- and 12- months post stroke. We will perform OCT imaging of the foveal region of the retina (6mm ETDRS) in both eyes of each patient. Images will be automatically segmented. Estimated thickness of the ganglion cell complex will be extracted and aligned with estimates of the blind field's visual sensitivity obtained from fundus-controlled MAIA perimetry. We will then compute a laterality index LI as follows: LIGCCT=(Tc-Ti)/(Tc+Ti) where Tc=thickness in the control lateral OCT quadrant, Ti=thickness in the impaired lateral OCT quadrant.
• Ganglion cell complex volume laterality [ Time Frame: baseline, 6 months, 12 months ]
  Change in volume of the ganglion cell complex will be measured by retinal optical coherence tomography (OCT) scans from baseline to 6- and 12- months post stroke. We will perform OCT imaging of the foveal region of the retina (6mm ETDRS) in both eyes of each patient. Images will be automatically segmented. Estimated volume of the ganglion cell complex will be extracted and aligned with estimates of the blind field's visual sensitivity obtained from fundus-controlled MAIA perimetry. We will then compute a laterality index as follows: LIGCCT=(Tc-Ti)/(Tc+Ti) where Tc=thickness in the control lateral OCT quadrant, Ti=thickness in the impaired lateral OCT quadrant.
• Optic Tract (OT) laterality [ Time Frame: baseline, 6 months, 12 months ]
  OT volume analysis will be performed from high resolution structural T1 MRI images of the brain. Mirrored masks of equal size will be hand-drawn over the OTs in each brain slice of a given subject, starting three slices posterior to the optic chiasm and continuing posteriorly until the OTs are no longer distinct from surrounding structures. The volume of each optic tract will be calculated from these masks by first establishing the maximum voxel intensity (range from 0 to 255) across the two OTs, then counting the number of voxels in each OT mask with brightness values between 5 and 85% of this maximum. We will then compute an OT laterality Index (LI85) to represent the relative difference in estimated volume between the two OTs of each participant, where LI85=(OTc-OTi)/(OTc+OTi), where OTc=number of voxels with brightness 5-85% of maximum in the contralesional OT and OTi = number of voxels with brightness 5-85% of maximum in the ipsilesional OT.

Current Other Pre-specified Outcome Measures (submitted: October 14, 2021)

• MAIA Visual Field Perimetry [ Time Frame: baseline, 6 months, 12 months ]
  We will measure the change in visual sensitivity (measured in decibels) at all locations tested by the system. These changes will be measured and compared between baseline, 6-months post stroke, and 12 months post stroke.** **NOTE: Our protocol allows for a +1 month variance for all timepoints.
• Humphrey 10-2 and 24-2 perimetry [ Time Frame: baseline, 6 months, 12 months ]
  We will measure the change in visual sensitivity (measured in decibels) at all locations tested by the system. These changes will be measured and compared between baseline, 6-months post stroke, and 12 months post stroke.** **NOTE: Our protocol allows for a +1 month variance for all timepoints.
• Goldmann perimetry [ Time Frame: baseline, 6 months, 12 months ]
  We will measure the change in area of vision (degrees squared) as encompassed by each isopter, measured by one of 3 different light stimuli. The 3 isopters we will compare are:

  1. I2e 1asb, 0.25 mm^2
  2. I4e 10asb, 0.25 mm^2
  3. V4e 1000asb, 64 mm^2

  These changes will be measured and compared between baseline, 6-months post stroke, and 12 months post stroke.** **NOTE: Our protocol allows for a +1 month variance for all timepoints.

Original Other Pre-specified Outcome Measures (submitted: March 12, 2021)

• MAIA Visual Field Perimetry [ Time Frame: baseline, 6 months, 12 months ]
  We will measure the change in visual sensitivity (measured in decibels) at all locations tested by the system. These changes will be measured and compared between baseline, 6-months post stroke, and 12 months post stroke.
• Humphrey 10-2 and 24-2 perimetry [ Time Frame: baseline, 6 months, 12 months ]
  We will measure the change in visual sensitivity (measured in decibels) at all locations tested by the system. These changes will be measured and compared between baseline, 6-months post stroke, and 12 months post stroke.
• Goldmann perimetry [ Time Frame: baseline, 6 months, 12 months ]
  We will measure the change in area of vision (degrees squared) as encompassed by each isopter, measured by one of 3 different light stimuli. The 3 isopters we will compare are:

  1. I2e 1asb, 0.25 mm^2
  2. I4e 10asb, 0.25 mm^2
  3. V4e 1000asb, 64 mm^2

  These changes will be measured and compared between baseline, 6-months post stroke, and 12 months post stroke.

Descriptive Information

• Brief Title: Visual Rehabilitation After Occipital Stroke
• Official Title: Visual Rehabilitation After Occipital Stroke
• Brief Summary: This research aims to examine changes in plastic potential of the visual system with time from stroke affecting primary visual cortex. We will measure structural and mechanistic aspects of progressive degeneration along the early visual pathways, correlating them with changes in visual performance, and in responsiveness to visual restoration training. This project will advance both scientific knowledge, as well as technical capability and clinical practices for restoring vision and quality of life for people suffering from cortical blindness.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Stroke, Ischemic
• Quadrantanopia
• Vision Loss Partial
• Visual Field Defect, Peripheral
• Peripheral Visual Field Defect of Both Eyes
• Peripheral Visual Field Defect
• Hemianopsia
• Hemianopia
• Homonymous Hemianopia
• Homonymous Hemianopsia
• Visual Fields Hemianopsia
• Occipital Lobe Infarct
• Quadrantanopsia
• Stroke Hemorrhagic

Intervention

• Device: Subacute Training in the intact field
  A computer software and chin-rest necessary to perform visual training will be loaned to each subject to be used at home. They will perform one to two daily training sessions in their home, consisting of 200-300 trials each. The visual task performed repetitively will involve discriminating the direction of motion of a small cloud of dots located at a predetermined location in the intact field. The computer program will automatically create a record of patient performance during each home training session. Subjects will train daily (about 40-60 minutes total), 5 to 7 days per week for at least one and up to 6 months.
• Device: Subacute Training in the blind field
  A computer software and chin-rest necessary to perform visual training will be loaned to each subject to be used at home. They will perform one to two daily training sessions in their home, consisting of 200-300 trials each. The visual task performed repetitively will involve discriminating the direction of motion of a small cloud of dots located at a predetermined location in the blind field. The computer program will automatically create a record of patient performance during each home training session. Subjects will train daily (about 40-60 minutes total), 5 to 7 days per week for at least one and up to 6 months.
• Device: Chronic Training in the blind field
  After the initial training period of one to six months, the same computer software will continue to be used for all subjects. The visual task performed repetitively will involve discriminating the direction of motion of a small cloud of dots located at a predetermined location in the blind field. The computer program will automatically create a record of patient performance during each home training session. Subjects will train daily (about 40-60 minutes total), 5 to 7 days per week for at least 6 months.

Study Arms

• Experimental: Training in the blind field
  Training in the blind field using specialized software
  Interventions:

  • Device: Subacute Training in the blind field
  • Device: Chronic Training in the blind field
• Experimental: Training in the intact field
  Training in the intact field using specialized software
  Interventions:

  • Device: Subacute Training in the intact field
  • Device: Chronic Training in the blind field

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 12, 2021): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 15, 2026
• Estimated Primary Completion Date: June 1, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Residents of US and Canada
• MRI and/or CT scans showing evidence of one-sided / unilateral stroke or stroke-like damage to the primary visual cortex or its immediate afferent white matter sustained less than 6-months prior to enrollment
• Reliable visual field defects in both eyes as measured by Humphrey, Macular Integrity Assessment (MAIA), Goldmann, and/or equivalent perimetry. This deficit must be large enough to enclose a 5-deg diameter visual stimulus.
• Ability to fixate on visual targets reliably for 1000ms (as demonstrated by visual fields, and verified in study participation)
• Willing and safely able to undergo magnetic resonance imaging (MRI) scanning
• Willing, able, and competent to provide informed consent
• Fluent in written and spoken English
• Cognitively able, responsible, and willing to complete daily visual training independently at home for several months.

Exclusion Criteria:

• Past or present ocular disease interfering with vision
• Best corrected visual acuity worse than 20/40 in either eye
• Presence of damage to the dorsal Lateral Geniculate Nucleus, as shown on MRI/CT scans
• Diffuse, whole brain degenerative processes
• Brain damage deemed by study staff to potentially interfere with training ability or outcome measures
• History of traumatic brain injury
• Documented history of drug/alcohol abuse
• Currently use of neuroactive medications which would impact training, as determined by PI
• Cognitive or seizure disorders
• One-sided attentional neglect
• Inability to perform the visual training exercises as directed

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Chrys Callan; 585-276-3426; Christine_Callan@URMC.Rochester.Edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04798924
• Other Study ID Numbers: 00005966; 3R01EY027314-06S2 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Krystel Huxlin, University of Rochester
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Rochester
• Original Study Sponsor: Same as current
• Collaborators: National Institutes of Health (NIH)
• Investigators: Not Provided
• PRS Account: University of Rochester
• Verification Date: January 2024