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Physician-scientists at NewYork-Presbyterian Hospital/Weill Cornell Medical Center are beginning a Phase III Clinical Trial of Ranirestat, a promising new investigational drug. Ranirestat is the first drug to address the underlying cause of diabetic sensorimotor polyneuropathy (DSP), also known as diabetic neuropathy, which is the most serious and common complication facing diabetics.

NewYork-Presbyterian/Weill Cornell is the only academic medical center in the tri-state metropolitan area chosen to participate in this clinical trial.

Half of the world's diabetics have DSP, and the disease can affect those with either type 1 or type 2 diabetes. Current medications for DSP only focus on treating the pain associated with the disease; they do not address the condition itself. There is currently no cure for DSP.

"We are excited to be taking part in this clinical trial," says Dr. Thomas Brannagan III, principal investigator for the trial and associate attending neurologist at NewYork-Presbyterian/Weill Cornell, and associate professor of clinical neurology at Weill Cornell Medical College. "The Phase II results were promising, and we are optimistic about the drug's potential."

DSP affects the nerves that control muscle movement and sense of touch. Symptoms may include sharp, burning, shooting, or stabbing pain; tingling or numbness in hands and feet; mild weakness; or loss of balance or coordination. DSP can lead to skin injuries – especially on the feet and generally sores or ulcers – which can become quite serious if left unattended. Each year, about 85,000 Americans need to have a limb amputated because of damage caused by DSP. About 64,000 of these amputations are preventable.

The exact cause of DSP is unknown. But, experiments show that an enzyme called aldose reductase interacts with the excessive glucose commonly found in diabetics and converts it to sorbitol. This process stresses the nerves until it damages them.

The drug being tested in this trial, Ranirestat, inhibits the powers of aldose reductase, and prevents it from turning glucose into sorbitol. In the drug's Phase II trial, Ranirestat reduced sorbitol levels by 65% to 84%. In addition, nerve function, as measured by nerve conduction studies, improved. This trial was headed by Dr. Vera Bril at the University of Toronto.

Many whose quality of life is brought down by DSP never see the disease coming. The majority of those with DSP initially experience no symptoms. And others don't realize that the tingling and numbness they feel in their hands and feet are signs of the disease.

A nerve conduction test, where certain parts of a person's arms and legs are stimulated and the nerve responses are recorded, can determine if someone has DSP.

The disease is most common in diabetics with poorly controlled blood sugar, and those who have had diabetes for more than 10 years.

The Phase III Trial

The Diabetic Sensorimotor Polyneuropathy (DSP) Trial at NewYork-Presbyterian/Weill Cornell will examine the safety and effectiveness of an investigational medication (Ranirestat) that is designed to slow the progression or possibly reverse the course of DSP.

Introductory testing will determine if a person actually has DSP, and those eligible for the trial will be asked to make 14 visits over the course of one year. Five of the 14 visits will include nerve conduction tests to determine if a patient's condition is improving, worsening, or staying the same. Participants are required to take a daily dose of the investigational medication (Ranirestat) or a placebo. Medication is given orally, and participants have a 3 in 4 chance of receiving the investigational medication. All participants may continue taking their other medications. Testing and medication is provided free of charge.

To be eligible for the trial, patients should:

• Have either type I or type II diabetes
• Be between 18 and 70 years old
• Have a hemoglobin A1c ≥ 7.0%, despite attempts to optimize glycemic control
• Have creatinine levels of
• Have normal AST and ALT, and alkaline phosphate

Patients who are or intend to become pregnant; patients who are nursing; patients with Hepatitis B, C, or HIV infection; or those with neuropathy from causes other than diabetes are not eligible.

The Diabetic Sensorimotor Polyneuropathy (DSP) Trial is being sponsored by Dainippon Pharmaceutical Co., Ltd., Japan, and is taking place at 26 sites throughout North America.

Patients interested in the trial at NewYork-Presbyterian/Weill Cornell should contact:
Michelle Renard, RN
Diabetic Neuropathy Research Center
Department of Neurology
NewYork-Presbyterian/Weill Cornell
Tel: 212-888-8516

Financial Disclosure: Weill Medical College of Cornell University is being paid by Dainippon to conduct this study, with Dr. Brannagan as the Principal Investigator. Neither Weill Cornell nor Dr. Brannagan has any other financial relationship with Dainippon.