Ignite Creation Date:
2024-05-05 @ 11:07 AM
Last Modification Date:
2024-10-26 @ 9:01 AM
Study NCT ID:
NCT00000159
Status:
COMPLETED
Last Update Posted:
2005-06-24
First Post:
1999-09-23
Brief Title:
Sorbinil Retinopathy Trial SRT
Sponsor:
National Eye Institute NEI
Organization:
National Eye Institute NEI
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
1999-10
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:
None
Brief Summary:
To evaluate the safety and efficacy of the investigational drug sorbinil an aldose reductase inhibitor in preventing the development of diabetic retinopathy and neuropathy in persons with insulin-dependent diabetes
Detailed Description:
During the last two decades vision researchers have studied intensively the role of the enzyme aldose reductase AR in diabetic cataract and in other diabetic complications The potentially damaging effects of AR in diabetes were first discovered in the lens fiber cells In these cells the enzyme catalyzes the reduction of high levels of glucose to sorbitol through the polyol pathway and initiates a sequence of events that eventually results in opacification of the lens Because sorbitol a sugar alcohol and fructose a subsequent product of glucose metabolism cannot readily diffuse across cell membranes they become trapped in lens fiber cells There they accumulate at unusually high levels and exert a significant osmotic stress causing an influx of water and swelling of the lens fibers Major electrolytic and osmotic changes then occur that lead to lens opacity
More recently the detection of AR in the pericytes of retinal capillaries -- cells that are involved very early in the evolution of diabetic retinopathy -- suggests that this enzyme may also play a role in the pathogenesis of this disorder Scientists now know that AR is present in nerve tissue and they speculate that in diabetes it induces the depletion of myo -inositol which leads to the lessening of nerve conduction velocity in diabetic neuropathy
Chemicals that inhibit aldose reductase have proved effective in preventing damage to the lens in preventing thickening of retinal capillary basement membranes in diabetic animals and in improving nerve conduction velocity values in patients with diabetic neuropathy Therefore it is possible that AR inhibitors also may be able to prevent delay or halt the development or progression of diabetic retinopathy
To test this hypothesis an AR inhibitor developed by Pfizer Inc sorbinil was studied in this clinical trial Other AR inhibitors underwent study in clinical trials sponsored by Ayerst and Alcon Initially 402 patients were randomized into the double-masked treatment period using a dosage schedule of one 250-mg tablet daily In 1985 recruitment was voluntarily halted by Pfizer because of several serious hypersensitivity reactions among patients taking sorbinil in clinical trials in the United States and Europe In November 1985 recruitment resumed using a titrated dosage schedule of 25 mg daily for 2 weeks followed by 75 mg daily for 2 weeks then 250 mg daily for the duration A total of 497 patients participated in the study
Followup visits were scheduled weekly for the first 4 weeks monthly for the next 2 months and every 3 months thereafter For patients assigned to the titration protocol additional visits were made at weeks 5 and 6 A complete history was recorded and a physical examination was conducted every 15 months electrocardiogram was recorded every 6 months In addition patients were cautioned to note any signs of hypersensitivity
Efficacy visits scheduled at 9-month intervals after the first visit at 12 months included fundus photographs visual acuity examinations according to the Early Treatment Diabetic Retinopathy Study ETDRS red blood cell sorbitol measure and assessment of coronary risk factor classification
The Sorbinil Retinopathy Trial SRT was a unique collaboration between private industry and the Federal government in designing funding and conducting a multicenter randomized clinical trial Pfizer Inc supported 10 of the 11 participating Clinical Centers provided the medication and funded the Data Coordinating Center and Fundus Photograph Reading Center The National Eye Institute funded the Policy Data and Safety Monitoring Committee and its own participating Clinical Center
More recently the detection of AR in the pericytes of retinal capillaries -- cells that are involved very early in the evolution of diabetic retinopathy -- suggests that this enzyme may also play a role in the pathogenesis of this disorder Scientists now know that AR is present in nerve tissue and they speculate that in diabetes it induces the depletion of myo -inositol which leads to the lessening of nerve conduction velocity in diabetic neuropathy
Chemicals that inhibit aldose reductase have proved effective in preventing damage to the lens in preventing thickening of retinal capillary basement membranes in diabetic animals and in improving nerve conduction velocity values in patients with diabetic neuropathy Therefore it is possible that AR inhibitors also may be able to prevent delay or halt the development or progression of diabetic retinopathy
To test this hypothesis an AR inhibitor developed by Pfizer Inc sorbinil was studied in this clinical trial Other AR inhibitors underwent study in clinical trials sponsored by Ayerst and Alcon Initially 402 patients were randomized into the double-masked treatment period using a dosage schedule of one 250-mg tablet daily In 1985 recruitment was voluntarily halted by Pfizer because of several serious hypersensitivity reactions among patients taking sorbinil in clinical trials in the United States and Europe In November 1985 recruitment resumed using a titrated dosage schedule of 25 mg daily for 2 weeks followed by 75 mg daily for 2 weeks then 250 mg daily for the duration A total of 497 patients participated in the study
Followup visits were scheduled weekly for the first 4 weeks monthly for the next 2 months and every 3 months thereafter For patients assigned to the titration protocol additional visits were made at weeks 5 and 6 A complete history was recorded and a physical examination was conducted every 15 months electrocardiogram was recorded every 6 months In addition patients were cautioned to note any signs of hypersensitivity
Efficacy visits scheduled at 9-month intervals after the first visit at 12 months included fundus photographs visual acuity examinations according to the Early Treatment Diabetic Retinopathy Study ETDRS red blood cell sorbitol measure and assessment of coronary risk factor classification
The Sorbinil Retinopathy Trial SRT was a unique collaboration between private industry and the Federal government in designing funding and conducting a multicenter randomized clinical trial Pfizer Inc supported 10 of the 11 participating Clinical Centers provided the medication and funded the Data Coordinating Center and Fundus Photograph Reading Center The National Eye Institute funded the Policy Data and Safety Monitoring Committee and its own participating Clinical Center
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