Fluoxetine for Visual Recovery After Ischemic Stroke (FLUORESCE)

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.

Study Overview

• Status: Terminated
• Conditions: Acute Stroke; Visual Field Loss
• Intervention / Treatment: Drug: Placebo; Drug: Fluoxetine

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14642
      • Strong Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching placebo	Drug: Placebo
Experimental: Fluoxetine; 20 mg fluoxetine capsule by mouth once daily for 90 days	Drug: Fluoxetine; Other Names: Prozac; Sarafem

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bogachan Sahin

Publications and helpful links

General Publications

• Zhang X, Kedar S, Lynn MJ, Newman NJ, Biousse V. Natural history of homonymous hemianopia. Neurology. 2006 Mar 28;66(6):901-5. doi: 10.1212/01.wnl.0000203338.54323.22.
• Schneider CL, Prentiss EK, Busza A, Williams ZR, Mahon BZ, Sahin B. FLUORESCE: A Pilot Randomized Clinical Trial of Fluoxetine for Vision Recovery After Acute Ischemic Stroke. J Neuroophthalmol. 2022 Jul 8. doi: 10.1097/WNO.0000000000001654. Online ahead of print.
• Saionz EL, Feldon SE, Huxlin KR. Rehabilitation of cortically induced visual field loss. Curr Opin Neurol. 2021 Feb 1;34(1):67-74. doi: 10.1097/WCO.0000000000000884.

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (Actual): August 1, 2020
• Study Completion (Actual): August 1, 2020

Study Registration Dates

• First Submitted: April 1, 2016
• First Submitted That Met QC Criteria: April 13, 2016
• First Posted (Estimate): April 14, 2016

Study Record Updates

• Last Update Posted (Actual): October 13, 2021
• Last Update Submitted That Met QC Criteria: September 16, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Acute ischemic stroke; Visual field loss; Fluoxetine; Selective serotonin reuptake inhibitor; Homonymous quadrantanopia; Homonymous hemianopia; Post-stroke recovery
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Fluoxetine
• Other Study ID Numbers: RSRB00058133

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No