Acute Stroke, Visual Field Loss
Conditions
Keywords
Acute ischemic stroke, Homonymous hemianopia, Homonymous quadrantanopia, Visual field loss, Post-stroke recovery, Fluoxetine, Selective serotonin reuptake inhibitor
Brief summary
The purpose of this study is to determine whether fluoxetine, a selective serotonin reuptake inhibitor commonly used for depression, enhances visual recovery after an acute ischemic stroke.
Interventions
DRUGFluoxetine
DRUGPlacebo
Sponsors
Bogachan Sahin
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* MRI-confirmed acute ischemic stroke resulting in an isolated homonymous visual field loss.
Exclusion criteria
* Known hypersensitivity to fluoxetine or other selective serotonin reuptake inhibitors * National Institutes of Health Stroke Scale score greater than 5 * Premorbid modified Rankin Scale score greater than 2 * Premorbid monocular or binocular visual field deficits * Premorbid retinopathy or optic neuropathy * Premorbid depression * History of cognitive impairment, dementia, or neurodegenerative disorder * History of seizure disorder * History of mania or hypomania * History of hyponatremia * History of angle-closure glaucoma or elevated intraocular pressure * Current alcohol abuse or impaired liver function * Current use of an antidepressant medication * Current use of a medication likely to have an adverse interaction with fluoxetine * Current use of a medication likely to impair post-stroke recovery * Contraindication to MRI * Pregnancy or lactation * Hemorrhagic transformation of the index stroke, resulting in mass effect * Enrollment in another clinical trial at the time of the index stroke
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in the Bionocularly Averaged Perimetric Mean Deviation | baseline to 6 months | 24-2 Humphrey perimetry was completed for each eye (Zeiss HFAIIi, Swedish Interactive Threshold Algorithm (SITA) Standard, size III white target, fixation enforced, corrected for near vision). The cutoff of a sensitivity of 10 dB to define sighted versus blind test locations was chosen. Perimetric mean deviation is a summary statistic calculated by measuring the deviation from the expected threshold value for stimulation at each point in the visual field and taking an average, with possible values ranging from +2 to -32 dB. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With >95% Recovery | 6 months | Recovery is an improvement in the blind visual field. Participants were counted if the percentage of visual field that was blind was reduced by 95%. |
| Functional Field Score | 6 months | This is a measure of functional peripheral vision in patients with otherwise normal visual acuity. It is calculated from perimetric data. Scores of 75-110 indicate near-normal to normal vision, 55-70 moderate low vision, 35-50 severe low vision, 15-30 profound low vision, and less than 15 near to total blindness. Hemianopia is considered severe low vision. |
| Percent Change in Mean Visual Function Questionnaire-25 Score | baseline to 6 months | The VFQ-25 consists of a base set of 25 vision targeted questions representing 11 vision-related constructs: global vision rating, difficulty with near vision activities, difficulty with distance vision activities, limitations in social functioning due to vision, role limitations due to vision, dependency on others due to vision, mental health symptoms due to vision, driving difficulties, limitations with peripheral and color vision, and ocular pain. The scores range from 0-100 with higher scores indicating better functioning. |
| Mean Percent Change in Field Points Tested | 6 months | Visual field recovery is defined as an improvement of more than 6 decibels (dB) in the threshold required to elicit a response at each point in the Humphrey visual field. This is based on the unidirectional test-retest variability of less than 3 dB reported in the Humphrey Field Analyzer manual. The endpoint will be an improvement in threshold values at test locations spanning more than 10 degrees horizontally or 15 degrees vertically in the Humphrey visual field in both eyes at 6 months, based on the definition of visual improvement used by Zhang et al. in their natural history study of stroke patients with hemianopia. |
| Median Modified Rankin Scale Score | 90 days | This is a functional outcome measure widely used in stroke clinical trials, with a score of 0 indicating no disability, 6 indicating death, and scores of 2 or less generally accepted to indicate a favorable functional outcome. |
| Post-stroke Changes in Cortical Visual Representation as Measured by Functional Magnetic Resonance Imaging | 6 months | Functional magnetic resonance imaging is a high-resolution imaging technique that can be used to measure cortical visual representation and functional activity during visual tasks using blood oxygen level-dependent responses. In stroke patients, this technique can be used to characterize the degree and nature of peri-lesional remapping of regions of the blind visual field during post-stroke visual recovery. Standard retinotopic mapping procedures will be used to determine the number of voxels in the early visual cortex that represent information about stimuli presented in the blind field of each patient. |
| Mean Percent Change in Post-stroke Retinal Nerve Fiber Layer Thickness | baseline to 6 months | This will be measured by spectral domain optical coherence tomography. Optical coherence tomography is a method of using low-coherence interferometry to determine the echo time delay and magnitude of backscattered light reflected off an object of interest. This method can be used to scan through the layers of a structured tissue sample such as the retina with very high axial resolution (3 to 15 μm), providing images demonstrating 3D structure. |
| Median Change in Patient Health Questionnaire-9 Score | baseline to 6 months | This is a self-report inventory used as a screening and diagnostic tool for depression (Appendix F). The 9 items are based on the 9 diagnostic criteria for depression included in the Diagnostic and Statistical Manual of Mental Disorders IV. The scales ranges from 0-27 with higher scores indicating worse outcome. |
Countries
United States
Participant flow
Pre-assignment details
5 participants were consented but 1 screen failed and 4 withdrew from the study before being randomized to an arm, received the intervention and before any data was collected.
Participants by arm
| Arm | Count |
|---|---|
| Fluoxetine 20 mg fluoxetine capsule by mouth once daily for 90 days
Fluoxetine | 5 |
| Placebo Matching placebo
Placebo | 7 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Fluoxetine | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 71 years | 61 years | 66 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 7 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Number of participants who received tissue plasminogen activator | 0 participants | 1 participants | 1 participants |
| Number of participants with diabetes | 3 participants | 2 participants | 5 participants |
| Number of participants with hypertension | 5 participants | 5 participants | 10 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 7 Participants | 12 Participants |
| Region of Enrollment United States | 5 participants | 7 participants | 12 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 4 Participants | 6 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 7 |
| other Total, other adverse events | 0 / 5 | 0 / 7 |
| serious Total, serious adverse events | 3 / 5 | 3 / 7 |
Outcome results
Primary
Percent Change in the Bionocularly Averaged Perimetric Mean Deviation
24-2 Humphrey perimetry was completed for each eye (Zeiss HFAIIi, Swedish Interactive Threshold Algorithm (SITA) Standard, size III white target, fixation enforced, corrected for near vision). The cutoff of a sensitivity of 10 dB to define sighted versus blind test locations was chosen. Perimetric mean deviation is a summary statistic calculated by measuring the deviation from the expected threshold value for stimulation at each point in the visual field and taking an average, with possible values ranging from +2 to -32 dB.
Time frame: baseline to 6 months
Population: One participant in the placebo arm withdrew from the study after month 1 but was included in the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Fluoxetine | Percent Change in the Bionocularly Averaged Perimetric Mean Deviation | 64.4 percent change in dB |
| Placebo | Percent Change in the Bionocularly Averaged Perimetric Mean Deviation | 26.0 percent change in dB |
Secondary
Functional Field Score
This is a measure of functional peripheral vision in patients with otherwise normal visual acuity. It is calculated from perimetric data. Scores of 75-110 indicate near-normal to normal vision, 55-70 moderate low vision, 35-50 severe low vision, 15-30 profound low vision, and less than 15 near to total blindness. Hemianopia is considered severe low vision.
Time frame: 6 months
Population: Data was not collected for this outcome measure.
Secondary
Mean Percent Change in Field Points Tested
Visual field recovery is defined as an improvement of more than 6 decibels (dB) in the threshold required to elicit a response at each point in the Humphrey visual field. This is based on the unidirectional test-retest variability of less than 3 dB reported in the Humphrey Field Analyzer manual. The endpoint will be an improvement in threshold values at test locations spanning more than 10 degrees horizontally or 15 degrees vertically in the Humphrey visual field in both eyes at 6 months, based on the definition of visual improvement used by Zhang et al. in their natural history study of stroke patients with hemianopia.
Time frame: 6 months
Population: One participant in the placebo arm withdrew from the study after month 1 but was included in the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Fluoxetine | Mean Percent Change in Field Points Tested | 72.4 percent of visual field points tested |
| Placebo | Mean Percent Change in Field Points Tested | 32.1 percent of visual field points tested |
Secondary
Mean Percent Change in Post-stroke Retinal Nerve Fiber Layer Thickness
This will be measured by spectral domain optical coherence tomography. Optical coherence tomography is a method of using low-coherence interferometry to determine the echo time delay and magnitude of backscattered light reflected off an object of interest. This method can be used to scan through the layers of a structured tissue sample such as the retina with very high axial resolution (3 to 15 μm), providing images demonstrating 3D structure.
Time frame: baseline to 6 months
Population: One participant in the placebo arm withdrew from the study after month 1 but was included in the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Fluoxetine | Mean Percent Change in Post-stroke Retinal Nerve Fiber Layer Thickness | -0.02 percent change in microns |
| Placebo | Mean Percent Change in Post-stroke Retinal Nerve Fiber Layer Thickness | -1.49 percent change in microns |
Secondary
Median Change in Patient Health Questionnaire-9 Score
This is a self-report inventory used as a screening and diagnostic tool for depression (Appendix F). The 9 items are based on the 9 diagnostic criteria for depression included in the Diagnostic and Statistical Manual of Mental Disorders IV. The scales ranges from 0-27 with higher scores indicating worse outcome.
Time frame: baseline to 6 months
Population: One participant in the placebo arm withdrew from the study after month 1 but was included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fluoxetine | Median Change in Patient Health Questionnaire-9 Score | -1 score on a scale |
| Placebo | Median Change in Patient Health Questionnaire-9 Score | 0 score on a scale |
Secondary
Median Modified Rankin Scale Score
This is a functional outcome measure widely used in stroke clinical trials, with a score of 0 indicating no disability, 6 indicating death, and scores of 2 or less generally accepted to indicate a favorable functional outcome.
Time frame: 90 days
Population: One participant in the placebo arm withdrew from the study after month 1 but was included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fluoxetine | Median Modified Rankin Scale Score | 1 score on a scale |
| Placebo | Median Modified Rankin Scale Score | 2 score on a scale |
Secondary
Number of Participants With >95% Recovery
Recovery is an improvement in the blind visual field. Participants were counted if the percentage of visual field that was blind was reduced by 95%.
Time frame: 6 months
Population: One participant in the placebo arm withdrew from the study after month 1 but was included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fluoxetine | Number of Participants With >95% Recovery | 3 participants |
| Placebo | Number of Participants With >95% Recovery | 1 participants |
Secondary
Percent Change in Mean Visual Function Questionnaire-25 Score
The VFQ-25 consists of a base set of 25 vision targeted questions representing 11 vision-related constructs: global vision rating, difficulty with near vision activities, difficulty with distance vision activities, limitations in social functioning due to vision, role limitations due to vision, dependency on others due to vision, mental health symptoms due to vision, driving difficulties, limitations with peripheral and color vision, and ocular pain. The scores range from 0-100 with higher scores indicating better functioning.
Time frame: baseline to 6 months
Population: One participant in the placebo arm withdrew from the study after month 1 but was included in the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Fluoxetine | Percent Change in Mean Visual Function Questionnaire-25 Score | -11.2 percent change of units on a scale |
| Placebo | Percent Change in Mean Visual Function Questionnaire-25 Score | -14.9 percent change of units on a scale |
Secondary
Post-stroke Changes in Cortical Visual Representation as Measured by Functional Magnetic Resonance Imaging
Functional magnetic resonance imaging is a high-resolution imaging technique that can be used to measure cortical visual representation and functional activity during visual tasks using blood oxygen level-dependent responses. In stroke patients, this technique can be used to characterize the degree and nature of peri-lesional remapping of regions of the blind visual field during post-stroke visual recovery. Standard retinotopic mapping procedures will be used to determine the number of voxels in the early visual cortex that represent information about stimuli presented in the blind field of each patient.
Time frame: 6 months
Population: Data was not collected for this outcome measure.