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        Anticonvulsant Topiramate May Target Underlying Diabetic Disease Process: Presented at ADA

        By Charlene Laino

        NEW ORLEANS, LA -- June 17, 2003 -- The antiepileptic drug topiramate may help to correct the underlying disease process in peripheral neuropathy, suggests a small, but intriguing, pilot study.

        Additionally, the anticonvulsant may improve components of the metabolic syndrome that often precedes development of type 2 diabetes, said Aaron I. Vinik, MD, PhD, director of the Strelitz Diabetes Research Institutes at Eastern Virginia Medical School in Norfolk, Virginia, United States.

        Dr. Vinik presented the study here on June 14th at the 63rd Annual Scientific Sessions of the American Diabetes Association.

        A previous study led by Dr. Vinik showed that topiramate appeared to improve outcomes in patients with peripheral neuropathy. What was particularly interesting, he said, is that other disorders common to diabetic patients also improved, including high body mass index (BMI) and high levels of cholesterol, triglyceride, and blood pressure.

        Dr. Vinik conducted a hypothesis-seeking trial and enrolled 11 patients with type 2 diabetes and C-fiber neuropathy. All patients were stabilized using conventional antidiabetic therapy and weaned off pain medication.

        The patients received 25 mg/day of topiramate, titrated over 42 days to the maximum tolerated dose or 100 mg/day. The patients remained on the anticonvulsant for a total of 8 weeks.

        By the end of trial, dendrite length and peroneal nerve amplitude increased, and total neuropathy scores decreased from 14 to 11.8, Dr. Vinik reported. "The most dramatic observation was that intraepidermal nerve fibers actually grew back," he said in an interview.

        In addition, mean diastolic blood pressure decreased from 82.7 mm Hg to 72.1 mm Hg. Baseline hemoglobin A1c levels decreased from 7.9% to 7.14%, and mean total cholesterol level decreased by about 10%, he said.

        "Topiramate may be the first drug to change the underlying biology of diabetic neuropathy as well as treat components of the metabolic syndrome," Dr. Vinik said.

        Fran Kaufman, MD, who completed her term as president of the American Diabetes Association at the meeting, said the findings are "intriguing and important."

        "When you look at the complications of diabetes, peripheral neuropathy is the one we have the least handle on," she said. "We knew already that some anticonvulsants have some modulating effects on peripheral neuropathy and it certainly looks like topiramate shows efficacy.

        "But what is so exciting about topiramate is that it may also have appetite-modulating effects and play multiple roles for people with diabetes," said Dr. Kaufman, who is head of the Center for Diabetes at Children's Hospital, in Los Angeles, California, United States.

        Dr. Vinik said he plans to test topiramate on 10 more patients in the open-label study before proceeding to a placebo-controlled, double-blind, randomized trial.

        Johnson & Johnson funded the research.


        [Study title: Topiramate Improves C-Fiber Neuropathy and Features of the Dysmetabolic Syndrome in Type 2 Diabetes. Abstract 660R]



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