Ignite Creation Date:
2024-05-06 @ 12:33 AM
Last Modification Date:
2024-10-26 @ 10:52 AM
Study NCT ID:
NCT01609881
Status:
WITHDRAWN
Last Update Posted:
2017-02-23
First Post:
2012-03-27
Brief Title:
The Role of Prostaglandins in the Progression of Diabetic Retinopathy
Sponsor:
Vanderbilt University
Organization:
Vanderbilt University Medical Center
Study Overview
Official Title:
The Role of Prostaglandins in the Progression of Diabetic Retinopathy and the Therapeutic Efficacy of Topical Ketorolac Acuvail
Status:
WITHDRAWN
Status Verified Date:
2017-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Due to lack of funding
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Prostaglandin
Brief Summary:
Objective of the research study
1 To measure anterior chamber and vitreous ketorolac Acuvail concentrations after topical administration in patients undergoing routine vitrectomy to determine the ability of the medication to penetrate into the anterior chamber and vitreous cavity and to compare these levels to the IC50 for the cyclooxygenase-1 and -2 enzymes COX-1 and COX-2
2 To measure vitreous concentrations of prostaglandin subtypes PGE PGD PGF and other inflammatory mediators Interleukin-1β IL-1β IL-6 IL-8 tumor necrosis factor TNF-α VEGF in both diabetic and nondiabetic patients undergoing vitrectomy
3 To determine if topical ketorolac Acuvail can penetrate the anterior chamber and vitreous cavity sufficiently to decrease levels of intraocular inflammatory mediators that have been shown to be elevated in diabetic patients
4 To serve as a precursor to a 5-year longitudinal clinical trial to determine if chronically administered topical ketorolac Acuvail can prevent delay or slow diabetic retinopathy
Research hypothesis
1 Ketorolac Acuvail will penetrate the anterior chamber and vitreous cavity sufficiently to achieve levels above the IC50 for COX-1 and COX-2
2 Prostaglandin and other inflammatory mediator levels in the anterior chamber and vitreous cavity will be significantly higher among diabetic patients than nondiabetic controls
3 Acuvail can significantly lower anterior chamber and vitreous cavity levels of prostaglandins and other inflammatory mediators in diabetic patients
1 To measure anterior chamber and vitreous ketorolac Acuvail concentrations after topical administration in patients undergoing routine vitrectomy to determine the ability of the medication to penetrate into the anterior chamber and vitreous cavity and to compare these levels to the IC50 for the cyclooxygenase-1 and -2 enzymes COX-1 and COX-2
2 To measure vitreous concentrations of prostaglandin subtypes PGE PGD PGF and other inflammatory mediators Interleukin-1β IL-1β IL-6 IL-8 tumor necrosis factor TNF-α VEGF in both diabetic and nondiabetic patients undergoing vitrectomy
3 To determine if topical ketorolac Acuvail can penetrate the anterior chamber and vitreous cavity sufficiently to decrease levels of intraocular inflammatory mediators that have been shown to be elevated in diabetic patients
4 To serve as a precursor to a 5-year longitudinal clinical trial to determine if chronically administered topical ketorolac Acuvail can prevent delay or slow diabetic retinopathy
Research hypothesis
1 Ketorolac Acuvail will penetrate the anterior chamber and vitreous cavity sufficiently to achieve levels above the IC50 for COX-1 and COX-2
2 Prostaglandin and other inflammatory mediator levels in the anterior chamber and vitreous cavity will be significantly higher among diabetic patients than nondiabetic controls
3 Acuvail can significantly lower anterior chamber and vitreous cavity levels of prostaglandins and other inflammatory mediators in diabetic patients
Detailed Description:
Patients who require vitrectomy for any indication and those meeting the inclusionexclusion criteria will be included Patients will be consented to participate in the study and for surgery
Nondiabetic patients will be included in one of two groups Twenty will receive topical ketorolac Acuvail preoperatively for 3 days and then samples will be taken at the time of surgery Twenty other patients will serve as controls for intraocular prostaglandin and cytokine levels to be compared to diabetic patients This group will not receive preoperative ketorolac Acuvail
Diabetic patients will be included in one of two groups Twenty patients will have intraocular prostaglandin and cytokine levels measured Twenty other patients will be in the interventional group to determine if topical ketorolac Acuvail can successfully lower intraocular prostaglandin and inflammatory cytokine levels
In all cases patients are undergoing vitreoretinal surgery as the surgical treatment of choice for their condition For this study undiluted samples will be drawn from the vitreous cavity and anterior chamber at the beginning of the vitrectomy These samples will be stored analyzed and frozen
Samples will be tested for prostaglandin levels in addition to other inflammatory cytokines and ketorolac levels
Three days of Acuvail given four times per day was chosen as previous studies have shown that one dose of ketorolac 04 achieves a peak aqueous concentration of 575 ngmL1 and that 12 doses over two days achieves an aqueous concentration of 1079 ngmL2 Both values are well above the IC50 for COX-1 53 to 75 ngmL and COX-2 339-452 ngmL The upper end of this dosing spectrum was chosen as more doses and a longer duration of therapy is likely required to achieve sufficient vitreous levels to inhibit COX-1 and COX-2 This dosing regimen was also used in another clinical study that assessed ketorolac levels and prostaglandin levels in the vitreous cavity after topical administration four times a day for three days preoperatively3
Nondiabetic patients will be included in one of two groups Twenty will receive topical ketorolac Acuvail preoperatively for 3 days and then samples will be taken at the time of surgery Twenty other patients will serve as controls for intraocular prostaglandin and cytokine levels to be compared to diabetic patients This group will not receive preoperative ketorolac Acuvail
Diabetic patients will be included in one of two groups Twenty patients will have intraocular prostaglandin and cytokine levels measured Twenty other patients will be in the interventional group to determine if topical ketorolac Acuvail can successfully lower intraocular prostaglandin and inflammatory cytokine levels
In all cases patients are undergoing vitreoretinal surgery as the surgical treatment of choice for their condition For this study undiluted samples will be drawn from the vitreous cavity and anterior chamber at the beginning of the vitrectomy These samples will be stored analyzed and frozen
Samples will be tested for prostaglandin levels in addition to other inflammatory cytokines and ketorolac levels
Three days of Acuvail given four times per day was chosen as previous studies have shown that one dose of ketorolac 04 achieves a peak aqueous concentration of 575 ngmL1 and that 12 doses over two days achieves an aqueous concentration of 1079 ngmL2 Both values are well above the IC50 for COX-1 53 to 75 ngmL and COX-2 339-452 ngmL The upper end of this dosing spectrum was chosen as more doses and a longer duration of therapy is likely required to achieve sufficient vitreous levels to inhibit COX-1 and COX-2 This dosing regimen was also used in another clinical study that assessed ketorolac levels and prostaglandin levels in the vitreous cavity after topical administration four times a day for three days preoperatively3
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