Ignite Creation Date:
2024-05-05 @ 5:00 PM
Last Modification Date:
2024-10-26 @ 9:27 AM
Study NCT ID:
NCT00369486
Status:
COMPLETED
Last Update Posted:
2016-08-26
First Post:
2006-08-25
Brief Title:
A Pilot Study of Peribulbar Triamcinolone Acetonide for Diabetic Macular Edema
Sponsor:
Jaeb Center for Health Research
Organization:
Jaeb Center for Health Research
Study Overview
Official Title:
A Pilot Study of Peribulbar Triamcinolone Acetonide for Diabetic Macular Edema
Status:
COMPLETED
Status Verified Date:
2016-08
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:
Peribulbar
Brief Summary:
The study involves the enrollment of patients over 18 years of age with diabetic macular edema involving the center of the macula who have not already been given maximal laser treatment
Patients with one study eye will be randomly assigned stratified by prior laser with equal probability to one of five treatment groups
1 Focal laser photocoagulation modified ETDRS technique
2 Posterior peribulbar injection of 40 mg triamcinolone Kenalog
3 Anterior peribulbar injection of 20 mg triamcinolone
4 Posterior peribulbar injection of 40 mg triamcinolone followed after one month by laser
5 Anterior peribulbar injection of 20 mg triamcinolone followed after one month by laser
For patients with two study eyes both eyes eligible at the time of randomization the right eye stratified by prior laser will be randomly assigned with equal probabilities to one of the five treatment groups listed above If the right eye was assigned to laser only then the left eye will be assigned to one of the four triamcinolone groups above with equal probability stratified by prior laser If the right eye was assigned to receive triamcinolone then the left eye will receive laser only
Triamcinolone acetonide will be the corticosteroid utilized in this study The triamcinolone acetonide preparation to be used is Kenalog Kenalog is manufactured by Bristol Myers Squibb and is approved by the Food and Drug Administration for intramuscular use for a variety of indications Peribulbar injections of Kenalog have been used for a wide variety of ocular conditions particularly uveitis and post-cataract extraction cystoid macular edema for many years
Two different triamcinolone regimens will be assessed in the study 40 mg injected posteriorly and 20 mg injected anteriorly There is no indication of which treatment regimen will be better Although the injection behind the eye is more common than the injection near the front of the eye the injection near the front of the eye has less risk of injuring the eye However it is possible that the injection near the front of the eye may increase eye pressure more frequently Little is known about which of the two injections decreases macular edema and improves vision more often
Patients enrolled into the study will be followed for three years and will have study visits 1 month 2 months 4 months 8 months and annually after receiving their assigned study treatment For the first 8 months of the study patients should only be retreated with their randomized treatment However if the patients visual acuity has decreased by 15 letters or more then any treatment may be given at the investigators discretion After completion of the 8-month visit treatment is at investigator discretion
The primary objective of this study is to obtain estimates of efficacy and safety outcomes for each of the treatment groups These estimates will provide a basis for the sample size estimation and hypothesis generation in a phase III trial
Patients with one study eye will be randomly assigned stratified by prior laser with equal probability to one of five treatment groups
1 Focal laser photocoagulation modified ETDRS technique
2 Posterior peribulbar injection of 40 mg triamcinolone Kenalog
3 Anterior peribulbar injection of 20 mg triamcinolone
4 Posterior peribulbar injection of 40 mg triamcinolone followed after one month by laser
5 Anterior peribulbar injection of 20 mg triamcinolone followed after one month by laser
For patients with two study eyes both eyes eligible at the time of randomization the right eye stratified by prior laser will be randomly assigned with equal probabilities to one of the five treatment groups listed above If the right eye was assigned to laser only then the left eye will be assigned to one of the four triamcinolone groups above with equal probability stratified by prior laser If the right eye was assigned to receive triamcinolone then the left eye will receive laser only
Triamcinolone acetonide will be the corticosteroid utilized in this study The triamcinolone acetonide preparation to be used is Kenalog Kenalog is manufactured by Bristol Myers Squibb and is approved by the Food and Drug Administration for intramuscular use for a variety of indications Peribulbar injections of Kenalog have been used for a wide variety of ocular conditions particularly uveitis and post-cataract extraction cystoid macular edema for many years
Two different triamcinolone regimens will be assessed in the study 40 mg injected posteriorly and 20 mg injected anteriorly There is no indication of which treatment regimen will be better Although the injection behind the eye is more common than the injection near the front of the eye the injection near the front of the eye has less risk of injuring the eye However it is possible that the injection near the front of the eye may increase eye pressure more frequently Little is known about which of the two injections decreases macular edema and improves vision more often
Patients enrolled into the study will be followed for three years and will have study visits 1 month 2 months 4 months 8 months and annually after receiving their assigned study treatment For the first 8 months of the study patients should only be retreated with their randomized treatment However if the patients visual acuity has decreased by 15 letters or more then any treatment may be given at the investigators discretion After completion of the 8-month visit treatment is at investigator discretion
The primary objective of this study is to obtain estimates of efficacy and safety outcomes for each of the treatment groups These estimates will provide a basis for the sample size estimation and hypothesis generation in a phase III trial
Detailed Description:
Diabetic retinopathy is a major cause of visual impairment in the United States Diabetic macular edema DME is a manifestation of diabetic retinopathy that produces loss of central vision Data from the Wisconsin Epidemiologic Study of Diabetic Retinopathy WESDR estimate that after 15 years of known diabetes the prevalence of diabetic macular edema is approximately 20 in patients with type 1 diabetes mellitus DM 25 in patients with type 2 DM who are taking insulin and 14 in patients with type 2 DM who do not take insulin
Diabetic macular edema results from abnormal leakage of macromolecules such as lipoproteins from retinal capillaries into the extravascular space followed by an oncotic influx of water into the extravascular space Abnormalities in the retinal pigment epithelium may also cause or contribute to diabetic macular edema These abnormalities may allow increased fluid from the choriocapillaries to enter the retina or they may decrease the normal efflux of fluid from the retina to the choriocapillaris The mechanism of breakdown of the blood retina barrier at the level of the retinal capillaries and the retinal pigment epithelium may be due to changes to tight junction proteins such as occludin
The increase in retinal capillary permeability and subsequent retinal edema may be the result of a breakdown of the blood retina barrier mediated in part by vascular endothelial growth factor VEGF a 45 kD glycoprotein Aiello et al demonstrated in an in vivo model that VEGF can increase vascular permeability Fifteen eyes of 15 albino Sprague-Dawley rats received an intravitreal injection of VEGF The effect of intravitreal administration of VEGF on retinal vascular permeability was assessed by vitreous fluorophotometry In all 15 eyes receiving an intravitreal injection of VEGF a statistically significant increase in vitreous fluorescein leakage was recorded In contrast control eyes which were fellow eyes injected with vehicle alone did not demonstrate a statistically significant increase in vitreous fluorescein leakage Vitreous fluorescein leakage in eyes injected with VEGF attained a maximum of 227 of control levels
Antonetti et al demonstrated that VEGF may regulate vessel permeability by increasing phosphorylation of tight junction proteins such as occludin and zonula occluden 1 Sprague-Dawley rats were given intravitreal injections of VEGF and changes in tight junction proteins were observed through Western blot analysis Treatment with alkaline phosphatase revealed that these changes were caused by a change in phosphorylation of tight junction proteins This model provides at the molecular level a potential mechanism for VEGF-mediated vascular permeability in the eye Similarly in human non-ocular disease states such as ascites VEGF has been characterized as a potent vascular permeability factor VPF
The normal human retina contains little or no VEGF however hypoxia causes upregulation of VEGF production Vinores et al using immunohistochemical staining for VEGF demonstrated that increased VEGF staining was found in retinal neurons and retinal pigment epithelium in human eyes with diabetic retinopathy
As the above discussion suggests attenuation of the effects of VEGF provides a rationale for treatment of macular edema associated with diabetic retinopathy Corticosteroids a class of substances with anti-inflammatory properties have been demonstrated to inhibit the expression of the VEGF gene In a study by Nauck et al the platelet-derived growth-factor PDGF induced expression of the VEGF gene in cultures of human aortic vascular smooth muscle cells was abolished by corticosteroids in a dose-dependent manner A separate study by Nauck et al demonstrated that corticosteroids abolished the induction of VEGF by the pro-inflammatory mediators PDGF and platelet-activating factor PAF in a time and dose-dependent manner This study was performed using primary cultures of human pulmonary fibroblasts and pulmonary vascular smooth muscle cells
As discussed above corticosteroids have been experimentally shown to down regulate VEGF production and possibly reduce breakdown of the blood-retinal barrier Similarly steroids have anti-angiogenic properties possibly due to attenuation of the effects of VEGF Both of these steroid effects have been utilized For example triamcinolone acetonide is often used clinically as a periocular injection for the treatment of cystoid macular edema CME secondary to uveitis or as a result of intraocular surgery In animal studies intravitreal triamcinolone acetonide has been used in the prevention of proliferative vitreoretinopathy and retinal neovascularization Intravitreal triamcinolone acetonide has been used clinically in the treatment of proliferative vitreoretinopathy and choroidal neovascularization
Diabetic macular edema results from abnormal leakage of macromolecules such as lipoproteins from retinal capillaries into the extravascular space followed by an oncotic influx of water into the extravascular space Abnormalities in the retinal pigment epithelium may also cause or contribute to diabetic macular edema These abnormalities may allow increased fluid from the choriocapillaries to enter the retina or they may decrease the normal efflux of fluid from the retina to the choriocapillaris The mechanism of breakdown of the blood retina barrier at the level of the retinal capillaries and the retinal pigment epithelium may be due to changes to tight junction proteins such as occludin
The increase in retinal capillary permeability and subsequent retinal edema may be the result of a breakdown of the blood retina barrier mediated in part by vascular endothelial growth factor VEGF a 45 kD glycoprotein Aiello et al demonstrated in an in vivo model that VEGF can increase vascular permeability Fifteen eyes of 15 albino Sprague-Dawley rats received an intravitreal injection of VEGF The effect of intravitreal administration of VEGF on retinal vascular permeability was assessed by vitreous fluorophotometry In all 15 eyes receiving an intravitreal injection of VEGF a statistically significant increase in vitreous fluorescein leakage was recorded In contrast control eyes which were fellow eyes injected with vehicle alone did not demonstrate a statistically significant increase in vitreous fluorescein leakage Vitreous fluorescein leakage in eyes injected with VEGF attained a maximum of 227 of control levels
Antonetti et al demonstrated that VEGF may regulate vessel permeability by increasing phosphorylation of tight junction proteins such as occludin and zonula occluden 1 Sprague-Dawley rats were given intravitreal injections of VEGF and changes in tight junction proteins were observed through Western blot analysis Treatment with alkaline phosphatase revealed that these changes were caused by a change in phosphorylation of tight junction proteins This model provides at the molecular level a potential mechanism for VEGF-mediated vascular permeability in the eye Similarly in human non-ocular disease states such as ascites VEGF has been characterized as a potent vascular permeability factor VPF
The normal human retina contains little or no VEGF however hypoxia causes upregulation of VEGF production Vinores et al using immunohistochemical staining for VEGF demonstrated that increased VEGF staining was found in retinal neurons and retinal pigment epithelium in human eyes with diabetic retinopathy
As the above discussion suggests attenuation of the effects of VEGF provides a rationale for treatment of macular edema associated with diabetic retinopathy Corticosteroids a class of substances with anti-inflammatory properties have been demonstrated to inhibit the expression of the VEGF gene In a study by Nauck et al the platelet-derived growth-factor PDGF induced expression of the VEGF gene in cultures of human aortic vascular smooth muscle cells was abolished by corticosteroids in a dose-dependent manner A separate study by Nauck et al demonstrated that corticosteroids abolished the induction of VEGF by the pro-inflammatory mediators PDGF and platelet-activating factor PAF in a time and dose-dependent manner This study was performed using primary cultures of human pulmonary fibroblasts and pulmonary vascular smooth muscle cells
As discussed above corticosteroids have been experimentally shown to down regulate VEGF production and possibly reduce breakdown of the blood-retinal barrier Similarly steroids have anti-angiogenic properties possibly due to attenuation of the effects of VEGF Both of these steroid effects have been utilized For example triamcinolone acetonide is often used clinically as a periocular injection for the treatment of cystoid macular edema CME secondary to uveitis or as a result of intraocular surgery In animal studies intravitreal triamcinolone acetonide has been used in the prevention of proliferative vitreoretinopathy and retinal neovascularization Intravitreal triamcinolone acetonide has been used clinically in the treatment of proliferative vitreoretinopathy and choroidal neovascularization
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| U10EY014231-09 | NIH | None | httpsreporternihgovquickSearchU10EY014231-09 |
| U10EY018817-03 | NIH | None | None |
| U10EY014229-07 | NIH | None | None |