Fluoxetine for Visual Recovery After Ischemic Stroke (FLUORESCE)

• ClinicalTrials.gov Identifier: NCT02737930
• Recruitment Status: Terminated
• First Posted: April 14, 2016
• Last Update Posted: August 25, 2020
• Sponsor: Bogachan Sahin
• Information provided by (Responsible Party): Bogachan Sahin, University of Rochester

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Acute Stroke; Visual Field Loss	Drug: Fluoxetine; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 17 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Fluoxetine for Visual Recovery After Ischemic Stroke
• Study Start Date: May 2016
• Actual Primary Completion Date: August 2020
• Actual Study Completion Date: August 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Improvement in size of visual field deficit (degrees) [ Time Frame: 6 months ]
   Improvement at each point in the Humphrey visual field will be defined as a decrease of more than 6 decibels (dB) in the threshold required to elicit a response at that location. This is based on the unidirectional test-retest variability of less than 3 dB reported in the Humphrey Field Analyzer manual. The primary 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.

Secondary Outcome Measures :

1. Improvement in size of visual field deficit (square degrees) [ Time Frame: 6 months ]
   Improvement at each point in the Humphrey visual field will be defined as a decrease of more than 6 dB in the threshold required to elicit a response at that location, as described in Outcome 1. The area of improvement in the visual field deficit will be measured in square degrees across test locations showing at least a 6-dB decrease in threshold values.
2. Improvement in parametric mean deviation [ Time Frame: 6 months ]
   Parametric 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.
3. Functional field score [ Time Frame: 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.
4. Visual Function Questionnaire-25 score [ Time Frame: 6 months ]
5. Patient Health Questionnaire-9 score [ Time Frame: 6 months ]
6. Modified Rankin Scale score [ Time Frame: 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.
7. Post-stroke changes in cortical visual representation as measured by functional magnetic resonance imaging [ Time Frame: 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.
8. Post-stroke changes in retinal nerve fiber layer thickness [ Time Frame: 6 months ]
   This will be measured by spectral domain optical coherence tomography.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, New York

Strong Memorial Hospital

Rochester, New York, United States, 14642

Sponsors and Collaborators

Bogachan Sahin

More Information

Publications:

Zhang X, Kedar S, Lynn MJ, Newman NJ, Biousse V. Natural history of homonymous hemianopia. Neurology. 2006 Mar 28;66(6):901-5.

• Responsible Party: Bogachan Sahin, Assistant Professor of Neurology, University of Rochester
• ClinicalTrials.gov Identifier: NCT02737930
• Other Study ID Numbers: RSRB00058133
• First Posted: April 14, 2016
• Last Update Posted: August 25, 2020
• Last Verified: August 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bogachan Sahin, University of Rochester:

Acute ischemic stroke; Homonymous hemianopia; Homonymous quadrantanopia; Visual field loss; Post-stroke recovery; Fluoxetine; Selective serotonin reuptake inhibitor

Additional relevant MeSH terms:

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Fluoxetine; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs; Antidepressive Agents, Second-Generation; Antidepressive Agents; Psychotropic Drugs; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors