Ignite Creation Date:
2024-05-05 @ 5:23 PM
Last Modification Date:
2024-10-26 @ 9:31 AM
Study NCT ID:
NCT00446381
Status:
COMPLETED
Last Update Posted:
2012-04-19
First Post:
2007-03-08
Brief Title:
Effect of MacugenPegaptanibon Surgical Outcomes and VEGF Levels in Diabetic Patients With PDR Diabetic Retinopathy or CSDME Macular Edema
Sponsor:
Lawson Health Research Institute
Organization:
Lawson Health Research Institute
Study Overview
Official Title:
Effect of Macugen Pegaptanib on Surgical Outcomes and Growth Factors Including Vascular Endothelial Growth Factor VEGF Levels in Patients With Proliferative Diabetic Retinopathy PDR and Clinically Significant Diabetic Macular Edema CSDME
Status:
COMPLETED
Status Verified Date:
2012-04
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:
PEGAP001
Brief Summary:
Patients with proliferative diabetic retinopathy or clinically significant diabetic macular edema requiring surgical intervention will receive a pre-operative injection of Macugen An initial pre-injection vitreous tap will be done in order to provide baseline VRGF 165 and cytokine levels At the onset of the vitrectomy a second vitreous sample will be taken to obtain intra-operative levels of Macugen VEGF 165 and cytokines
Detailed Description:
Diabetes is one of the leading causes of blindness in North America Diabetic retinopathy PDR is characterized by disruption of the normal microvascular circulation in the retina and results in the production of neovascularization and increased microvascular permeability Similarly clinically significant diabetic macular edema CSDME results in loss of central visual acuity
Many patients with these conditions despite treatment will go on to develop vitreous hemorrhage or tractional changes that require surgical intervention suchas vitrectomy andor vitrectomy with membrane peeling in the attempt to both restore vision and prevent further visual loss or re-establish the normal macular anatomy and improve patient visual acuity
Although multiple etiologic factors are involved in the early changes seen in diabetic retinopathy and maculopathy it has been shown that VEGF is the primary angiogenic growth factor implicated in the development of neovascularization in PRD and in increased vascular permeability resulting in CSDME VEGF levels have been found to correlate tightly with the extent of diabetic retinopathy and introduction of VEGF into normal primate eyes can induce diabetic retinopathy Although several isoforms of VEGF exist isoform 165 VEGF 165 is the most pathogenic form of VEGF and therefore inhibition of VEGF 165 may play a significant role in modulating diabetic retinopathy and maculopathy
Macugen is a VEGF antagonist anti-VEGF pegylated aptamer which binds to VEGF 165 with high specificity and affinity In vitro pharmacology studies have shown that Macugen binds to the amino acid isoform VEGF 165 and inhibits it from binding to its cellular receptors As a consequence Macugen blocks signalling events and disrupts the cascade of proliferative and vascular permeability responses associated with the binding of VEGF 165 to endothelial cells This effect has been clearly proven in Phase 3 trials for patients with age-related macular degeneration AMD resulting in inhibition of vascular development and decrease in vascular leakage
Although diabetic retinopathy represents a different challenge than AMD the underlying pathogenic factors are similar in the role and effects of VEGF Regression of retinal neovascularization after Macugen therapy in diabetic individuals has been shown Phase 2 studies have been completed and Phase 3 studies are currently underway in patients with diabetic macular edema to evaluate the efficacy of Macugen to restore vision in patients with CSDME These studies are ongoing but exclude patients in whom vitrectomy has been performed or is planned in the near future due to tractional effects on the macula from epiretinal membranes or vitreomacular traction syndrome No studies have been done to date in patients with PDR or CSDME to quantify the reduction of intravitreal VEGF 165 levels in these patients following intravitreal Macugen injection or to evaluate the effects of VEGF 165 blockade on the neovascular regression and surgical outcome in patients with extensive diabetic proliferative neovascularization
The goal of this study is to quantify the reduction of intravitreal VEGF 165 levels in patients following intravitreal Macugen injection pre-operatively and determine the level of Macugen in the vitreous cavity after variable time intervals 24 6 or 8 weeks
Many patients with these conditions despite treatment will go on to develop vitreous hemorrhage or tractional changes that require surgical intervention suchas vitrectomy andor vitrectomy with membrane peeling in the attempt to both restore vision and prevent further visual loss or re-establish the normal macular anatomy and improve patient visual acuity
Although multiple etiologic factors are involved in the early changes seen in diabetic retinopathy and maculopathy it has been shown that VEGF is the primary angiogenic growth factor implicated in the development of neovascularization in PRD and in increased vascular permeability resulting in CSDME VEGF levels have been found to correlate tightly with the extent of diabetic retinopathy and introduction of VEGF into normal primate eyes can induce diabetic retinopathy Although several isoforms of VEGF exist isoform 165 VEGF 165 is the most pathogenic form of VEGF and therefore inhibition of VEGF 165 may play a significant role in modulating diabetic retinopathy and maculopathy
Macugen is a VEGF antagonist anti-VEGF pegylated aptamer which binds to VEGF 165 with high specificity and affinity In vitro pharmacology studies have shown that Macugen binds to the amino acid isoform VEGF 165 and inhibits it from binding to its cellular receptors As a consequence Macugen blocks signalling events and disrupts the cascade of proliferative and vascular permeability responses associated with the binding of VEGF 165 to endothelial cells This effect has been clearly proven in Phase 3 trials for patients with age-related macular degeneration AMD resulting in inhibition of vascular development and decrease in vascular leakage
Although diabetic retinopathy represents a different challenge than AMD the underlying pathogenic factors are similar in the role and effects of VEGF Regression of retinal neovascularization after Macugen therapy in diabetic individuals has been shown Phase 2 studies have been completed and Phase 3 studies are currently underway in patients with diabetic macular edema to evaluate the efficacy of Macugen to restore vision in patients with CSDME These studies are ongoing but exclude patients in whom vitrectomy has been performed or is planned in the near future due to tractional effects on the macula from epiretinal membranes or vitreomacular traction syndrome No studies have been done to date in patients with PDR or CSDME to quantify the reduction of intravitreal VEGF 165 levels in these patients following intravitreal Macugen injection or to evaluate the effects of VEGF 165 blockade on the neovascular regression and surgical outcome in patients with extensive diabetic proliferative neovascularization
The goal of this study is to quantify the reduction of intravitreal VEGF 165 levels in patients following intravitreal Macugen injection pre-operatively and determine the level of Macugen in the vitreous cavity after variable time intervals 24 6 or 8 weeks
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 |
|---|---|---|---|
| Health Canada Control 108753 | None | None | None |