The University of Minnesota and Harvard University will partner on a new clinical trial to study a potential treatment for kidney disease in people with type 1 diabetes; a study that will be funded by a $24.3 million grant from the National Institutes of Health (NIH).
Researchers believe the findings from this study – both from the perspective of public health and that of individuals with diabetes – will be significant as researchers seek a better understanding around improving the health of people with diabetes and kidney complications.
The five-year trial, part of the Preventing Early Renal Function Loss in Diabetes (PERL) consortium, is designed to evaluate the possible benefits of allopurinol in reducing kidney function loss in people with Type 1 diabetes. Allopurinol is an FDA-approved drug that can lower uric acid, and previous research from the Joslin Diabetes Center and other investigators has linked higher levels of uric acid to the risk of kidney complications in diabetes.
Michael Mauer, M.D., a professor of pediatrics and medicine at the University of Minnesota Medical School and Alessandro Doria, M.D., Ph.D., M.P.H., an associate professor of medicine at Harvard Medical School and associate professor in the Department of Epidemiology at the Harvard School of Public Health, will lead the trial. Luiza Caramori, M.D., M.Sc., Ph.D., an assistant professor of medicine and pediatrics at the University of Minnesota Medical School, will direct the study.
“Smaller studies have suggested the benefits of slowing kidney function decline in patients with chronic kidney disease, but PERL is positioned to provide a much more definitive answer to this important question,” said Mauer.
Kidney disease poses one of the greatest burdens for people with type 1 diabetes, with 10 to 15 percent of patients developing end stage renal disease (ESRD), meaning that they need hemodialysis or a renal transplant to survive.
According to Mauer, diabetes is responsible for more than 45 percent of the more than 115,000 new ESRD cases in the USA, and the number of people with diabetes and kidney failure rose by 61 percent between 2000 and 2010.
“This study has large human suffering, public health and health cost implications,” said Mauer, “because currently, tight control of blood sugar and blood pressure are the only prevention tools we have. But as many as 50 percent of people with diabetes cannot achieve optimal blood sugar control and blood pressure control is only partially effective.”
“The goal of this study is to see if we can slow down the decline of kidney function by decreasing uric acid levels and find a new way of preventing kidney complications in people with diabetes,” added Doria. “Data indicates that moderately high serum uric acid levels predispose to diabetic kidney disease. However, we don’t know whether this is due to uric acid itself or to something else that goes together with it. That’s why this study is important – to determine if uric acid is the culprit or not.”
This study will include approximately 500 patients with type 1 diabetes who are at increased risk of losing kidney function. Half of the patients will be randomly assigned to take allopurinol and the other half will be assigned to placebo for three years. Study recruitment could begin as early as this month.
If the PERL consortium can demonstrate that allopurinol is capable of halting or slowing down loss of kidney function in people with type one diabetes, there will be a generic and safe medication to prevent or delay kidney failure by intervening at the early stages of kidney disease.
“If we see a significant benefit of allopurinol on slowing progression of diabetic kidney disease, this will become a standard addition to the treatment of diabetic kidney complications especially given that allopurinol is relatively inexpensive and safe,” said Caramori.
Prior to being awarded this grant, Doria and Mauer together with Peter Rossing, M.D., head of research at the Steno Diabetes Center and Affiliated Professor at Aarhus University in Denmark, conducted a small pilot of this study with the support of the Juvenile Diabetes Research Foundation (JDRF). From this, they have already established the infrastructure and procedures, which allows them to start recruiting patients for the study as early as October.
The research will be conducted at institutions in the PERL consortium, composed by the Joslin Diabetes Center, University of Minnesota, the Universities of Colorado, Toronto, and Michigan, Northwestern University, Albert Einstein College of Medicine and the Steno Diabetes Center in Denmark. The funding will be distributed to the eight clinical centers, plus a data center in Michigan and a central laboratory in Minnesota.