Ignite Creation Date:
2024-05-06 @ 6:12 PM
Last Modification Date:
2024-10-26 @ 2:43 PM
Study NCT ID:
NCT05581498
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-03-15
First Post:
2022-10-12
Brief Title:
Glaucoma Exercise as Medicine Study GEMS
Sponsor:
Johns Hopkins University
Organization:
Johns Hopkins University
Study Overview
Official Title:
Glaucoma Exercise as Medicine Study GEMS
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
GEMS
Brief Summary:
Project Summary Abstract
While lifestyle changes particularly exercise have been suggested to protect against damage to ganglion cells in animal models definitive evidence demonstrating its benefits in humans is lacking Here in a group of individuals with ganglion cell damage from glaucoma and a separate control group without significant eye disease the investigators study the effects of a remotely delivered exercise training program by a trained exercise physiologist consisting of resistance training combined with cycling on a stationary bike Three outcomes will be examined to evaluate if exercise might be of potential long-term benefit in protecting ganglion cells In Aim 1 the investigators will examine the trials primary outcome a comparison of the pointwise change in the visual field VF sensitivity over the exercise period compared to a preceding usual activity period Given the subjective nature of VF testing Electroretinogram ERG testing will be employed as a more objective secondary outcome Together these outcomes will determine if neuro recovery is possible with exercise in individuals with GC damage from glaucoma as has been demonstrated for Intraocular pressure IOP-lowering and more recently nicotinamide and if neuro enhancement improvement in the function above an already-normal level is possible in adults without eye disease In Aim 2 the investigators will examine if an exercise produces physiologic changes in the human eye glaucoma and control which would give mechanistic plausibility for a neuroprotective effect Specifically the investigators will compare exercise-induced changes in large vessel retinal blood flow the density of and flux within perfused capillaries large-vessel arterial-venous oxygen O2 saturation gradients inner retinal O2 metabolism and serum levels of brain-derived neurotrophic factor BDNF to changes occurring in the preceding usual activity control period Finally in Aim 3 the investigators will examine if exercise benefits quality of life QOL in individuals with VF damage from glaucoma within specific domains mobility ocular discomfort and mood independent of changes in visual function Together these findings will provide important information regarding whether exercise produces short-term changes in eyes which suggests possible long-term protection against ganglion cell damage
While lifestyle changes particularly exercise have been suggested to protect against damage to ganglion cells in animal models definitive evidence demonstrating its benefits in humans is lacking Here in a group of individuals with ganglion cell damage from glaucoma and a separate control group without significant eye disease the investigators study the effects of a remotely delivered exercise training program by a trained exercise physiologist consisting of resistance training combined with cycling on a stationary bike Three outcomes will be examined to evaluate if exercise might be of potential long-term benefit in protecting ganglion cells In Aim 1 the investigators will examine the trials primary outcome a comparison of the pointwise change in the visual field VF sensitivity over the exercise period compared to a preceding usual activity period Given the subjective nature of VF testing Electroretinogram ERG testing will be employed as a more objective secondary outcome Together these outcomes will determine if neuro recovery is possible with exercise in individuals with GC damage from glaucoma as has been demonstrated for Intraocular pressure IOP-lowering and more recently nicotinamide and if neuro enhancement improvement in the function above an already-normal level is possible in adults without eye disease In Aim 2 the investigators will examine if an exercise produces physiologic changes in the human eye glaucoma and control which would give mechanistic plausibility for a neuroprotective effect Specifically the investigators will compare exercise-induced changes in large vessel retinal blood flow the density of and flux within perfused capillaries large-vessel arterial-venous oxygen O2 saturation gradients inner retinal O2 metabolism and serum levels of brain-derived neurotrophic factor BDNF to changes occurring in the preceding usual activity control period Finally in Aim 3 the investigators will examine if exercise benefits quality of life QOL in individuals with VF damage from glaucoma within specific domains mobility ocular discomfort and mood independent of changes in visual function Together these findings will provide important information regarding whether exercise produces short-term changes in eyes which suggests possible long-term protection against ganglion cell damage
Detailed Description:
1 A Our proposed work lies on the premise that 1 preventing visual field VF damage will preserve functionality and quality of life QoL 2 small degrees of VF improvement are possible in eyes with ganglion cells GC damage using glaucoma as a model and therapies yielding such improvements may provide long-term neuroprotection 3 retinal vascular parameters and neuroprotective agents BDNF contribute to GC damage and therapies that improve these parameters ie exercise can prevent the onset or worsen of VF damage and 4 QoL can be improved in patients with GC damage independent of the severity of VF damage Based on this premise the investigators propose to establish if exercise can create measurable improvements in GC function Aim 1 and improve retinal vascular parameters and levels of neuroprotective factors BDNF Aim 2 which would suggest it may be useful in protecting against further GC damage preserving the quality of life Finally the investigators also propose that exercise can improve elements of QoL independent of vision changes Aim 3
2 Background Several studies provided evidence that sedentary lifestyles contribute significantly to the development of a significant risk of age-related disease and complications The investigators previous work on 141 older adults with manifest Glaucoma and glaucoma suspects has shown slower VF loss rates with moderate-vigorous physical activity PA and non-sedentary activities 26 hours of increased PA and additional 5000 daily steps have shown a decrease in the VF loss up to 10 in the treated group of glaucoma patients with more steps 0007 decibel dByear1000 daily steps P 0001 moderate to vigorous activity 0003 decibel dB year10 more minutes of moderate-to-vigorous activity per day P 0001 and more non-sedentary activity 0007 decibel dB year30 more minutes of non-sedentary time per day P 0005 Another study demonstrated a strong association between decreased activity fragmentation with the severity of VF damage reflecting lower physiologic functions each 5- decibel dB decrement in integrated visual field IVF sensitivity was associated with 163 fewer active minutesday P 005 There is a strong need to establish the association between ocular physiology and PA Therefore more mechanistic approaches demonstrating the vascular physiology related to improved visual functions and neuroprotection in Glaucoma are needed More practical methods for effective therapy and long-term randomized controlled trials are required to prove a cause-effect relationship
3 Study design including the sequence and timing of study procedures This study is designed as a single-center prospective study in which all subjects are evaluated over consecutive 12-week usual activity control and exercise intervention periods This design was chosen over 1 a cross-over design which would be challenged by some participants assigned initially to exercise and continuing to exercise after crossing over into usual activity or 2 a comparison of exercise and waitlist-control groups 3 20 normally sighted control participants aged 21 years or above will be included for pilot testing The idea behind including the younger age group is to test the study procedures validity and give insight into the projects true scope Also there is less data on how these age groups may respond to interventions being studied The latter would require a much larger sample size necessitating a multicenter study where the proposed imaging would not be available due to greater across-subject vs within-subject variability particularly in ERG testing Notably ERG testing is a particularly important study outcome as it objectively measures GC function to confirm that improvements in the primary outcome measure VF sensitivity are not due to improved attention cognition or reaction speed The investigators also include both a control no eye disease and glaucoma model disease of GC damage group as 1 changes in GC function may occur from the recovery of damaged but alive GCs neuro recovery or improvement in GC function regardless of the level of damage neuro enhancement - a distinction that can be made only by the inclusion of normal controls 2 improvement in physiological parameters especially blood flow in the control group will serve as a positive control given that improvements in retinal blood flow have been seen with a high-speed circuit resistance training program in older adults without eye disease and 3 comparisons of exercise-related changes in the control and glaucoma groups will confirm that the putative physiological benefits of exercise are not lost in eyes with GC damage from glaucoma
Participants will perform 6 study visits in which the participants will be evaluated by 1 Visual fields VFs 2 Electroretinogram ERG 3 Laser speckle contrast imaging LSCI 4 Optical coherence tomography angiography OCTA 5 Visible light optical coherence tomography VisOCT 6 QoL using the Glaucoma computer adaptive test GlauCAT and 7 fitness testing via the physical working capacity PWC test Visits will occur in clustered pairs before and after the usual activity and after the exercise During the exercise program participants will complete three 75 exercise sessions weekly in remote groups connected to each other and the instructor via zoom link
The investigators will recruit 75 glaucoma patients and 75 normally sighted controls aged 21 to 80 from the Johns Hopkins Wilmer Eye Institute to have 60 subjects in each group who pass initial entry screening and 50 in each group completing all study procedures Glaucoma subjects will be diagnosed with primary open-angle glaucoma based on clinical exams Optical coherence tomography OCT imaging and VF testing Evidence of glaucoma should be present in both eyes with one eye demonstrating a mean deviation MD between -5 and -15 decibel dB Controls will be recruited from home cohabitants spousespartners of patients visiting the Wilmer Eye Institute patients seen for routine eye care general eye exam refraction and if necessary community volunteers Controls will be required to have normal visual acuity VA 2040 or better and contrast sensitivity logCS150 in each eye and no self-reported ocular conditions other than mild cataract dry eye refractive error or other non-visually significant conditions ocular allergies pinguecula etc
In both groups individuals will be excluded with a history of any of the following in either eye diabetic retinopathy retinal detachment uveitis retinal artery or vein occlusion central serous retinopathy amblyopia or other conditions resulting in a corrected VA worse than 2040 controls will also be excluded if the participants have a history of glaucoma suspect glaucoma or ocular hypertension Other exclusion criteria are uncontrolled blood pressure Systolic blood pressure SBP160 or Diastolic blood pressure DBP 100 incisional surgery ocular or non-ocular in the past 6 months comorbidities making exercise program impossible cigarette smoking body mass index BMI 18 or 42 kgm2 or pregnancy Patients reporting moderatevigorous activity for more than 90 minutesweek will also be ineligible Suitability for exercise will be determined using the Physical Activity Readiness Questionnaire Plus PARQ Study recruitment will occur at the Johns Hopkins Wilmer Eye Institute either the East Baltimore campus clinic or 2 of the busiest satellite clinics - Green Spring Station and Columbia located 12 and 24 miles from the East Baltimore campus At least 3 of the 6 study visits will occur at the Wilmer Eye Institute East Baltimore Campus where the Optical coherence tomography angiography OCT-A and visible light optical coherence tomography Vis OCT machines are located The remaining study visits can be conducted at the Columbia or Green Spring Station clinics if more convenient for the patient The exercise intervention will occur remotely over Zoom with the exercise physiologist located in the participants home or office and the study participant located in the participants home
2 Background Several studies provided evidence that sedentary lifestyles contribute significantly to the development of a significant risk of age-related disease and complications The investigators previous work on 141 older adults with manifest Glaucoma and glaucoma suspects has shown slower VF loss rates with moderate-vigorous physical activity PA and non-sedentary activities 26 hours of increased PA and additional 5000 daily steps have shown a decrease in the VF loss up to 10 in the treated group of glaucoma patients with more steps 0007 decibel dByear1000 daily steps P 0001 moderate to vigorous activity 0003 decibel dB year10 more minutes of moderate-to-vigorous activity per day P 0001 and more non-sedentary activity 0007 decibel dB year30 more minutes of non-sedentary time per day P 0005 Another study demonstrated a strong association between decreased activity fragmentation with the severity of VF damage reflecting lower physiologic functions each 5- decibel dB decrement in integrated visual field IVF sensitivity was associated with 163 fewer active minutesday P 005 There is a strong need to establish the association between ocular physiology and PA Therefore more mechanistic approaches demonstrating the vascular physiology related to improved visual functions and neuroprotection in Glaucoma are needed More practical methods for effective therapy and long-term randomized controlled trials are required to prove a cause-effect relationship
3 Study design including the sequence and timing of study procedures This study is designed as a single-center prospective study in which all subjects are evaluated over consecutive 12-week usual activity control and exercise intervention periods This design was chosen over 1 a cross-over design which would be challenged by some participants assigned initially to exercise and continuing to exercise after crossing over into usual activity or 2 a comparison of exercise and waitlist-control groups 3 20 normally sighted control participants aged 21 years or above will be included for pilot testing The idea behind including the younger age group is to test the study procedures validity and give insight into the projects true scope Also there is less data on how these age groups may respond to interventions being studied The latter would require a much larger sample size necessitating a multicenter study where the proposed imaging would not be available due to greater across-subject vs within-subject variability particularly in ERG testing Notably ERG testing is a particularly important study outcome as it objectively measures GC function to confirm that improvements in the primary outcome measure VF sensitivity are not due to improved attention cognition or reaction speed The investigators also include both a control no eye disease and glaucoma model disease of GC damage group as 1 changes in GC function may occur from the recovery of damaged but alive GCs neuro recovery or improvement in GC function regardless of the level of damage neuro enhancement - a distinction that can be made only by the inclusion of normal controls 2 improvement in physiological parameters especially blood flow in the control group will serve as a positive control given that improvements in retinal blood flow have been seen with a high-speed circuit resistance training program in older adults without eye disease and 3 comparisons of exercise-related changes in the control and glaucoma groups will confirm that the putative physiological benefits of exercise are not lost in eyes with GC damage from glaucoma
Participants will perform 6 study visits in which the participants will be evaluated by 1 Visual fields VFs 2 Electroretinogram ERG 3 Laser speckle contrast imaging LSCI 4 Optical coherence tomography angiography OCTA 5 Visible light optical coherence tomography VisOCT 6 QoL using the Glaucoma computer adaptive test GlauCAT and 7 fitness testing via the physical working capacity PWC test Visits will occur in clustered pairs before and after the usual activity and after the exercise During the exercise program participants will complete three 75 exercise sessions weekly in remote groups connected to each other and the instructor via zoom link
The investigators will recruit 75 glaucoma patients and 75 normally sighted controls aged 21 to 80 from the Johns Hopkins Wilmer Eye Institute to have 60 subjects in each group who pass initial entry screening and 50 in each group completing all study procedures Glaucoma subjects will be diagnosed with primary open-angle glaucoma based on clinical exams Optical coherence tomography OCT imaging and VF testing Evidence of glaucoma should be present in both eyes with one eye demonstrating a mean deviation MD between -5 and -15 decibel dB Controls will be recruited from home cohabitants spousespartners of patients visiting the Wilmer Eye Institute patients seen for routine eye care general eye exam refraction and if necessary community volunteers Controls will be required to have normal visual acuity VA 2040 or better and contrast sensitivity logCS150 in each eye and no self-reported ocular conditions other than mild cataract dry eye refractive error or other non-visually significant conditions ocular allergies pinguecula etc
In both groups individuals will be excluded with a history of any of the following in either eye diabetic retinopathy retinal detachment uveitis retinal artery or vein occlusion central serous retinopathy amblyopia or other conditions resulting in a corrected VA worse than 2040 controls will also be excluded if the participants have a history of glaucoma suspect glaucoma or ocular hypertension Other exclusion criteria are uncontrolled blood pressure Systolic blood pressure SBP160 or Diastolic blood pressure DBP 100 incisional surgery ocular or non-ocular in the past 6 months comorbidities making exercise program impossible cigarette smoking body mass index BMI 18 or 42 kgm2 or pregnancy Patients reporting moderatevigorous activity for more than 90 minutesweek will also be ineligible Suitability for exercise will be determined using the Physical Activity Readiness Questionnaire Plus PARQ Study recruitment will occur at the Johns Hopkins Wilmer Eye Institute either the East Baltimore campus clinic or 2 of the busiest satellite clinics - Green Spring Station and Columbia located 12 and 24 miles from the East Baltimore campus At least 3 of the 6 study visits will occur at the Wilmer Eye Institute East Baltimore Campus where the Optical coherence tomography angiography OCT-A and visible light optical coherence tomography Vis OCT machines are located The remaining study visits can be conducted at the Columbia or Green Spring Station clinics if more convenient for the patient The exercise intervention will occur remotely over Zoom with the exercise physiologist located in the participants home or office and the study participant located in the participants home
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None