New NIH Prevention Trial Targets Very High-Risk Relatives

To better understand the development of type 1 diabetes and to evaluate preventive interventions, researchers have initiated clinical studies in the relatives of individuals affected by the disease. A new clinical trial through TrialNet, a multi-center consortium sponsored by the National Institutes of Health, will be testing a drug’s efficacy in stopping the progression of type 1 diabetes in high-risk relatives of people currently diagnosed with the disease.

The Phase I trial will evaluate whether a well-known anti-CD3 drug called teplizumab can halt or reverse the natural time course of the disease in people whose immune systems have already begun to attack the insulin-producing cells of the pancreas. Within five years, it is estimated that 75 percent of these high-risk relatives will go on to develop type 1 diabetes.

“To my knowledge, there is no other trial in the world that is testing prevention of type 1 diabetes in this very select population,” says Kevan Herold, M.D., principal investigator of the clinical trial and professor of immunobiology and medicine at Yale University. “It’s the most exciting trial I have ever done.”

In 2002, the NIH sponsored a clinical trial that showed that teplizumab can preserve beta cell function in people recently diagnosed with the disease. The results of the study, which were published in The New England Journal of Medicine, were confirmed three years later, in 2005, by a clinical trial conducted in Europe, also in people within three months of diagnosis.

“We think that using teplizumab during the pre-clinical stage of the disease, just before people are likely to be diagnosed, will have a greater impact on disease progression,” says Jay Skyler, M.D., chairman of TrialNet and a professor of medicine, pediatrics, and psychology at the University of Miami’s Miller School of Medicine. “With the promising results of earlier trials using teplizumab in recent-onset patients, we anticipate that we can block the development of diabetes before it even begins.”

“The trial is a huge effort because it requires many centers and institutions collaborating with each other to find people at very high risk for diabetes,” says Dr. Herold. “But this outreach to the community and the time and resources needed to pull something like this off will be worth it if we can someday find a drug that reverses the natural progression of the disease.”