Vision Disorders
Conditions
Keywords
Exercise, Retinal Degeneration, Neuropharmacology, Brain-Derived Neurotrophic Factor, Biometry, Immunochemistry, Molecular Biology, Neurosciences, Ophthalmology
Brief summary
This study will determine whether blood biomarker changes predict sight-saving benefits of exercise.
Detailed description
Investigators of the Atlanta VA Center for Visual and Neurocognitive Rehabilitation (CVNR) find a very high prevalence of blinding diseases in the aging Veteran population. There are few treatments for the disorders that threaten our Veterans' eyesight. The work proposed here is the first step in determining whether exercise can be used by aging Veterans as an inexpensive and self-controlled therapy for vision loss. In order to translate exercise therapy for vision into the clinic, the investigators need to identify biomarkers that can be used to predict visual benefits. Though human and animal studies show that aerobic exercise is beneficial to specific central and peripheral nervous system functions, effects on the retina and vision were unknown until the investigators recently discovered that treadmill exercise directly protects retinal neurons in mice undergoing light-induced retinal degeneration (LIRD). The investigators found that exercise increased levels of brain-derived neurotrophic factor (BDNF) a blood protein in the blood, brain and eyes, whereas treatment of mice with a BDNF inhibitor prevented the protective effects of exercise. For this study, the investigators will assess visual outcomes and serum biomarkers (e.g, BDNF) in 60 subjects age 18-89 before, during, and after aerobic exercise. Subjects currently enrolled in a 12-week study (under Institutional Review Board (IRB) 56726) examining the effects of aerobic exercise on cognition will have visual testing (ERG, visual acuity, contrast sensitivity, and OCT) and blood collection prior to, during and after the standardized 12-week aerobic exercise regimen to determine whether circulating biomarker levels and visual outcomes are correlated and whether biomarker levels are altered as predicted in animal studies. This study will determine whether biomarker changes predict sight-saving benefits of exercise. As opposed to surgery or pharmacological treatments, exercise programs provide a means for Veterans to exert some control over their visual disease progression and will increase their overall health.
Interventions
BEHAVIORALAerobic exercise
Stationary bicycle ergometer @ 50-80% of maximal heart rate reserve for 20 minutes to 45 minutes
BEHAVIORALBalance exercise
Instructor-led exercises done in a group setting for strengthening, balance, flexibility
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 89 Years
Healthy volunteers
Yes
Inclusion criteria
* English speaking * Aged 18 to 89 * Sedentary as defined by \< 120 min/week of aerobic exercise over prior 3 months * Non-demented (MMSE 24)
Exclusion criteria
* Severe diabetes requiring insulin * Cognitive-executive function deficit (MoCA \< 26)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Visual Acuity - Mean Acuity Change | 12 weeks | Early Treatment Diabetic Retinopathy Study (ETDRS) chart was used. Higher scores mean a better outcome. The number of correct responses (e.g., number of letters read correctly) from a subject assessed prior to start of the first session of the the 12 week study was subtracted from the number of correct responses elicited at the end of the last session of the study. The means of these differences for each study group (Balance Training vs Aerobic Exercise) were compared by two-tailed t-test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Contrast Sensitivity | 12 weeks | Contrast sensitivity: The contrast sensitivity of the subjects will be measured with the Pelli-Robson Chart or Contrast Sensitivity Chart following the instructions provided with the chart. The two sides of the Pelli-Robson Chart have different letter sequences but are otherwise identical. The chart should be illuminated as uniformly as possible, so that the luminance of the white areas is between 80 and 120 cd/ m2 with no glare. The patient should sit directly in front of the chart at a distance of 1 meter (use the same 1 meter string as for visual acuity testing to measure the eye-to-chart distance). Subjects should be prevented from seeing the chart until the contrast sensitivity testing actually begins. Subjects should wear their best distance correction. |
| Concentration of Brain-Derived Neurotrophic Factor (BDNF) in Serum. | 12 weeks | Blood will be drawn prior to and after exercise sessions. From this, serum levels of brain derived neurotrophic factor (BDNF) will measured by immunoenzymatic assay. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aerobic Exercise Exercise 3 times a week
Aerobic exercise: Stationary bicycle ergometer @ 50-80% of maximal heart rate reserve for 20 minutes to 45 minutes | 6 |
| Balance Training Group balance training 3 times a week
Balance exercise: Instructor-led exercises done in a group setting for strengthening, balance, flexibility | 8 |
| Total | 14 |
Baseline characteristics
| Characteristic | Balance Training | Total | Aerobic Exercise |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 14 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 73.1 years STANDARD_DEVIATION 4 | 73.4 years STANDARD_DEVIATION 6.1 | 73.7 years STANDARD_DEVIATION 8.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) White | 2 Participants | 4 Participants | 2 Participants |
| Region of Enrollment United States | 8 Participants | 14 Participants | 6 Participants |
| Sex: Female, Male Female | 7 Participants | 13 Participants | 6 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 8 |
| other Total, other adverse events | 0 / 6 | 0 / 8 |
| serious Total, serious adverse events | 0 / 6 | 0 / 8 |
Outcome results
Primary
Visual Acuity - Mean Acuity Change
Early Treatment Diabetic Retinopathy Study (ETDRS) chart was used. Higher scores mean a better outcome. The number of correct responses (e.g., number of letters read correctly) from a subject assessed prior to start of the first session of the the 12 week study was subtracted from the number of correct responses elicited at the end of the last session of the study. The means of these differences for each study group (Balance Training vs Aerobic Exercise) were compared by two-tailed t-test.
Time frame: 12 weeks
Population: As per baseline analysis population description.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aerobic Exercise | Visual Acuity - Mean Acuity Change | 7.333 Letters read correctly | Standard Deviation 8.501 |
| Balance Training | Visual Acuity - Mean Acuity Change | -4.875 Letters read correctly | Standard Deviation 10.58 |
p-value: <0.05t-test, 2 sided
Secondary
Concentration of Brain-Derived Neurotrophic Factor (BDNF) in Serum.
Blood will be drawn prior to and after exercise sessions. From this, serum levels of brain derived neurotrophic factor (BDNF) will measured by immunoenzymatic assay.
Time frame: 12 weeks
Secondary
Contrast Sensitivity
Contrast sensitivity: The contrast sensitivity of the subjects will be measured with the Pelli-Robson Chart or Contrast Sensitivity Chart following the instructions provided with the chart. The two sides of the Pelli-Robson Chart have different letter sequences but are otherwise identical. The chart should be illuminated as uniformly as possible, so that the luminance of the white areas is between 80 and 120 cd/ m2 with no glare. The patient should sit directly in front of the chart at a distance of 1 meter (use the same 1 meter string as for visual acuity testing to measure the eye-to-chart distance). Subjects should be prevented from seeing the chart until the contrast sensitivity testing actually begins. Subjects should wear their best distance correction.
Time frame: 12 weeks