FLUORESCE: Fluoxetine for Visual Recovery After Ischemic Stroke

• Sponsor: Bogachan Sahin (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02737930
• Collaborator: (none)
• Enrollment: 17
• Location: 1
• Arms: 2
• Duration (Months): 51
• Patients Per Site Per Month: 0.3

Study Details

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
• 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 1, 2016
• Actual Primary Completion Date: Aug 1, 2020
• Actual Study Completion Date: Aug 1, 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. 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 Outcome Measures

1. 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.

2. 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%.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Strong Memorial Hospital	Rochester	New York	United States	14642

Sponsors and Collaborators

• Bogachan Sahin

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 15, 2016
• Informed Consent Form - Aug 27, 2019

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: Apr 14, 2016
• Last Update Posted: Oct 13, 2021
• Last Verified: Sep 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Bogachan Sahin, Assistant Professor of Neurology, 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; Ischemic Stroke; Fluoxetine

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Fluoxetine	Placebo
Arm/Group Description	20 mg fluoxetine capsule by mouth once daily for 90 days Fluoxetine	Matching placebo Placebo
Period Title: Overall Study
STARTED	5	7
COMPLETED	5	6
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Fluoxetine	Placebo	Total
Arm/Group Description	20 mg fluoxetine capsule by mouth once daily for 90 days Fluoxetine	Matching placebo Placebo	Total of all reporting groups
Overall Participants	5	7	12
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	71	61	66
Sex: Female, Male (Count of Participants)
Female	1 20%	1 14.3%	2 16.7%
Male	4 80%	6 85.7%	10 83.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	5 100%	7 100%	12 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	5 100%	7 100%	12 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	5 100%	7 100%	12 100%
Number of participants who received tissue plasminogen activator (participants) [Number]
Number [participants]	0 0%	1 14.3%	1 8.3%
Number of participants with diabetes (participants) [Number]
Number [participants]	3 60%	2 28.6%	5 41.7%
Number of participants with hypertension (participants) [Number]
Number [participants]	5 100%	5 71.4%	10 83.3%

Outcome Measures

1. Primary Outcome

Title	Percent Change in the Bionocularly Averaged Perimetric Mean Deviation
Description	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

Outcome Measure Data

Analysis Population Description

One participant in the placebo arm withdrew from the study after month 1 but was included in the analysis.

Arm/Group Title	Fluoxetine	Placebo
Arm/Group Description	20 mg fluoxetine capsule by mouth once daily for 90 days Fluoxetine	Matching placebo Placebo
Measure Participants	5	7
Mean (95% Confidence Interval) [percent change in dB]	64.4	26.0

2. Secondary Outcome

Title	Mean Percent Change in Field Points Tested
Description	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

Outcome Measure Data

Analysis Population Description

One participant in the placebo arm withdrew from the study after month 1 but was included in the analysis.

Arm/Group Title	Fluoxetine	Placebo
Arm/Group Description	20 mg fluoxetine capsule by mouth once daily for 90 days Fluoxetine	Matching placebo Placebo
Measure Participants	5	7
Mean (95% Confidence Interval) [percent of visual field points tested]	72.4	32.1

3. Secondary Outcome

Title	Number of Participants With >95% Recovery
Description	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

Outcome Measure Data

Analysis Population Description

One participant in the placebo arm withdrew from the study after month 1 but was included in the analysis.

Arm/Group Title	Fluoxetine	Placebo
Arm/Group Description	20 mg fluoxetine capsule by mouth once daily for 90 days Fluoxetine	Matching placebo Placebo
Measure Participants	5	7
Number [participants]	3 60%	1 14.3%

4. Secondary Outcome

Title	Functional Field Score
Description	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

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome measure.

Arm/Group Title	Fluoxetine	Placebo
Arm/Group Description	20 mg fluoxetine capsule by mouth once daily for 90 days Fluoxetine	Matching placebo Placebo
Measure Participants	0	0

5. Secondary Outcome

Title	Percent Change in Mean Visual Function Questionnaire-25 Score
Description	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

Outcome Measure Data

Analysis Population Description

One participant in the placebo arm withdrew from the study after month 1 but was included in the analysis.

Arm/Group Title	Fluoxetine	Placebo
Arm/Group Description	20 mg fluoxetine capsule by mouth once daily for 90 days Fluoxetine	Matching placebo Placebo
Measure Participants	5	7
Mean (95% Confidence Interval) [percent change of units on a scale]	-11.2	-14.9

6. Secondary Outcome

Title	Median Change in Patient Health Questionnaire-9 Score
Description	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

Outcome Measure Data

Analysis Population Description

One participant in the placebo arm withdrew from the study after month 1 but was included in the analysis.

Arm/Group Title	Fluoxetine	Placebo
Arm/Group Description	20 mg fluoxetine capsule by mouth once daily for 90 days Fluoxetine	Matching placebo Placebo
Measure Participants	5	7
Median (Inter-Quartile Range) [score on a scale]	-1	0

7. Secondary Outcome

Title	Median Modified Rankin Scale Score
Description	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

Outcome Measure Data

Analysis Population Description

One participant in the placebo arm withdrew from the study after month 1 but was included in the analysis.

Arm/Group Title	Fluoxetine	Placebo
Arm/Group Description	20 mg fluoxetine capsule by mouth once daily for 90 days Fluoxetine	Matching placebo Placebo
Measure Participants	5	7
Median (Inter-Quartile Range) [score on a scale]	1	2

8. Secondary Outcome

Title	Post-stroke Changes in Cortical Visual Representation as Measured by Functional Magnetic Resonance Imaging
Description	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

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome measure.

Arm/Group Title	Fluoxetine	Placebo
Arm/Group Description	20 mg fluoxetine capsule by mouth once daily for 90 days Fluoxetine	Matching placebo Placebo
Measure Participants	0	0

9. Secondary Outcome

Title	Mean Percent Change in Post-stroke Retinal Nerve Fiber Layer Thickness
Description	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

Outcome Measure Data

Analysis Population Description

One participant in the placebo arm withdrew from the study after month 1 but was included in the analysis.

Arm/Group Title	Fluoxetine	Placebo
Arm/Group Description	20 mg fluoxetine capsule by mouth once daily for 90 days Fluoxetine	Matching placebo Placebo
Measure Participants	5	7
Mean (95% Confidence Interval) [percent change in microns]	-0.02	-1.49

Adverse Events

Time Frame	6 months
Arm/Group Title	Fluoxetine		Placebo
Arm/Group Description	20 mg fluoxetine capsule by mouth once daily for 90 days Fluoxetine		Matching placebo Placebo
All Cause Mortality
	Fluoxetine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/7 (0%)
Serious Adverse Events
	Fluoxetine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/5 (60%)		3/7 (42.9%)
Nervous system disorders
seizure	2/5 (40%)		0/7 (0%)
Skin and subcutaneous tissue disorders
rash	0/5 (0%)		1/7 (14.3%)
Vascular disorders
hemorrhagic transformation	0/5 (0%)		1/7 (14.3%)
stroke	0/5 (0%)		1/7 (14.3%)
transient ischemic attack	1/5 (20%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	Fluoxetine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/7 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.