Trial Outcomes & Findings for Fluoxetine for Visual Recovery After Ischemic Stroke (NCT NCT02737930)

Last Updated: 2021-10-13

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

17 participants

Primary outcome timeframe

baseline to 6 months

Results posted on

2021-10-13

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Fluoxetine 20 mg fluoxetine capsule by mouth once daily for 90 days Fluoxetine	Placebo Matching placebo Placebo
Overall Study STARTED	5	7
Overall Study COMPLETED	5	6
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Fluoxetine 20 mg fluoxetine capsule by mouth once daily for 90 days Fluoxetine	Placebo Matching placebo Placebo
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Fluoxetine for Visual Recovery After Ischemic Stroke

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fluoxetine n=5 Participants 20 mg fluoxetine capsule by mouth once daily for 90 days Fluoxetine	Placebo n=7 Participants Matching placebo Placebo	Total n=12 Participants Total of all reporting groups
Age, Continuous	71 years n=5 Participants	61 years n=7 Participants	66 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	5 participants n=5 Participants	7 participants n=7 Participants	12 participants n=5 Participants
Number of participants who received tissue plasminogen activator	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Number of participants with diabetes	3 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants
Number of participants with hypertension	5 participants n=5 Participants	5 participants n=7 Participants	10 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline to 6 months

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

Outcome measures

Outcome measures
Measure	Fluoxetine n=5 Participants 20 mg fluoxetine capsule by mouth once daily for 90 days Fluoxetine	Placebo n=7 Participants Matching placebo Placebo
Percent Change in the Bionocularly Averaged Perimetric Mean Deviation	64.4 percent change in dB Interval 30.2 to 98.6	26.0 percent change in dB Interval 0.2 to 51.7

SECONDARY outcome

Timeframe: 6 months

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

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.

Outcome measures

Outcome measures
Measure	Fluoxetine n=5 Participants 20 mg fluoxetine capsule by mouth once daily for 90 days Fluoxetine	Placebo n=7 Participants Matching placebo Placebo
Mean Percent Change in Field Points Tested	72.4 percent of visual field points tested Interval 36.1 to 108.7	32.1 percent of visual field points tested Interval 6.8 to 57.4

SECONDARY outcome

Timeframe: 6 months

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

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%.

Outcome measures

Outcome measures
Measure	Fluoxetine n=5 Participants 20 mg fluoxetine capsule by mouth once daily for 90 days Fluoxetine	Placebo n=7 Participants Matching placebo Placebo
Number of Participants With >95% Recovery	3 participants	1 participants

SECONDARY outcome

Timeframe: 6 months

Population: Data was not collected for this outcome measure.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline to 6 months

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

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.

Outcome measures

Outcome measures
Measure	Fluoxetine n=5 Participants 20 mg fluoxetine capsule by mouth once daily for 90 days Fluoxetine	Placebo n=7 Participants Matching placebo Placebo
Percent Change in Mean Visual Function Questionnaire-25 Score	-11.2 percent change of units on a scale Interval -23.2 to 0.8	-14.9 percent change of units on a scale Interval -27.3 to -2.5

SECONDARY outcome

Timeframe: baseline to 6 months

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

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.

Outcome measures

Outcome measures
Measure	Fluoxetine n=5 Participants 20 mg fluoxetine capsule by mouth once daily for 90 days Fluoxetine	Placebo n=7 Participants Matching placebo Placebo
Median Change in Patient Health Questionnaire-9 Score	-1 score on a scale Interval -1.0 to -0.8	0 score on a scale Interval -1.5 to 1.5

SECONDARY outcome

Timeframe: 90 days

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

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.

Outcome measures

Outcome measures
Measure	Fluoxetine n=5 Participants 20 mg fluoxetine capsule by mouth once daily for 90 days Fluoxetine	Placebo n=7 Participants Matching placebo Placebo
Median Modified Rankin Scale Score	1 score on a scale Interval 1.0 to 2.0	2 score on a scale Interval 0.5 to 2.0

SECONDARY outcome

Timeframe: 6 months

Population: Data was not collected for this outcome measure.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline to 6 months

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

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.

Outcome measures

Outcome measures
Measure	Fluoxetine n=5 Participants 20 mg fluoxetine capsule by mouth once daily for 90 days Fluoxetine	Placebo n=7 Participants Matching placebo Placebo
Mean Percent Change in Post-stroke Retinal Nerve Fiber Layer Thickness	-0.02 percent change in microns Interval -1.96 to 1.92	-1.49 percent change in microns Interval -3.26 to 0.28

Adverse Events

Fluoxetine

Serious events: 3 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Fluoxetine n=5 participants at risk 20 mg fluoxetine capsule by mouth once daily for 90 days Fluoxetine	Placebo n=7 participants at risk Matching placebo Placebo
Vascular disorders hemorrhagic transformation	0.00% 0/5 • 6 months	14.3% 1/7 • 6 months
Vascular disorders stroke	0.00% 0/5 • 6 months	14.3% 1/7 • 6 months
Vascular disorders transient ischemic attack	20.0% 1/5 • 6 months	0.00% 0/7 • 6 months
Nervous system disorders seizure	40.0% 2/5 • 6 months	0.00% 0/7 • 6 months
Skin and subcutaneous tissue disorders rash	0.00% 0/5 • 6 months	14.3% 1/7 • 6 months

Other adverse events

Adverse event data not reported

Additional Information

Bogachan Sahin

University of Rochester

Phone: (585) 275-2530

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place