A multicenter international study chaired by a Joslin Diabetes Center investigator and reported in the July issue of the American Diabetes Association's journal Diabetes brings hopeful news to the 18 million people in the United States -- and millions more worldwide -- with type 1 or type 2 diabetes.
Initial results of the Phase III clinical trial demonstrated that 32 milligrams per day of ruboxistaurin (RBX) was well tolerated and may reduce the risk of moderate vision loss, especially in patients with diabetic macular edema.
Loss of vision is a common complication of diabetes and results from two primary conditions: diabetic retinopathy and diabetic macular edema. In diabetic retinopathy, tiny blood vessels in the retina become damaged. While early in the disease (the nonproliferative stage) there are often no symptoms, over time new, abnormal blood vessels proliferate and bleed easily. If untreated, proliferative diabetic retinopathy can cause severe vision loss. In diabetic macular edema, leaky blood vessels cause swelling in the macula -- the part of the retina responsible for sharp central vision. Current laser treatments for diabetic eye diseases may help prevent severe vision loss, but because the laser destroys areas of the retina, side effects of treatment may include reduction in peripheral vision or night vision.
The purpose of the PKC-Diabetic Retinopathy Study (DRS) was to evaluate the safety and effect of an oral treatment, RBX, on retinopathy progression or visual loss in patients with moderately severe to very severe nonproliferative diabetic retinopathy. In the double-masked, randomized multiple-dose study, 252 patients with type 1 or type 2 diabetes received either RBX or a placebo over a period of 3-4 years. The study measured the effect of three orally administered doses of RBX (8, 16, or 32 mg/day) on progression of diabetic retinopathy, moderate visual loss and sustained moderate visual loss. The study was conducted at Joslin Diabetes Center, medical centers across the United States as well as in Canada, Denmark, the Netherlands, and United Kingdom.
The oral treatment RBX inhibits, or blocks, the activity of an enzyme called protein kinase C. PKC is essential to the normal production of energy in the body, but a specific form of the enzyme -- PKC-beta -- has been linked to diabetic complications of the eye and other parts of the body. Thus RBX was designed to be selective for the single PKC-beta isoform, a fact that contributes to the inhibitor's excellent safety profile, according to the researchers.