Fluoxetine for Visual Recovery After Ischemic Stroke

Study Overview
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Brief Summary
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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.

Official Title
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Fluoxetine for Visual Recovery After Ischemic Stroke

Conditions
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Acute Stroke, Visual Field Loss

Intervention / Treatment
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* Drug: Fluoxetine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluoxetine<br>20 mg fluoxetine capsule by mouth once daily for 90 days | Drug: Fluoxetine<br> <br> * Other names: Sarafem;|
| Placebo Comparator: Placebo<br>Matching placebo | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | baseline to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 6 months | 
| 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%. | 6 months | 
| 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. | 6 months | 
| 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. | baseline to 6 months | 
| 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. | baseline to 6 months | 
| 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. | 90 days | 
| 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. | 6 months | 
| 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. | baseline to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute ischemic stroke, Homonymous hemianopia, Homonymous quadrantanopia, Visual field loss, Post-stroke recovery, Fluoxetine, Selective serotonin reuptake inhibitor