John Lachin, professor of biostatistics, epidemiology and statistics at the George Washington University, has been awarded a five-year, $134 million grant from the National Institute of Health's National Institute of Diabetes and Digestive and Kidney Diseases to conduct a clinical trial examining the long-term effectiveness of several glucose-lowering medications for treatment of people with type 2 diabetes. The grant sets a record as the largest sum award GW has ever received.
Dr. Lachin, interim director of GW's Biostatistics Center in Rockville, Md., is principal investigator for the grant along with David M. Nathan, M.D., director of the Diabetes Center at the Massachusetts General Hospital and professor of medicine at Harvard Medical School, both in Boston. The pair, working jointly with investigators at GW and Massachusetts General Hospital, recruited a network of more than 40 clinical centers nationwide to participate in the study.
"This funding is tremendously important to healthcare as it could result in more effective treatment of diabetes," said Leo Chalupa, vice president of research at GW. "The award of this grant signifies that the Biostatistics Center is a premier facility of its type and that Dr. Lachin and the project team deserve tremendous credit for putting together this successful investigator-initiated grant application. An award of this magnitude will increase the future ranking of GW among the country's research universities and bring us closer to the goal set by President Knapp of becoming a top tier research institution."
Titled Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study (grant # 1 U01 DK-098246), the clinical trial will directly compare the most commonly used medications to treat type 2 diabetes.
"Type 2 diabetes is an epidemic that threatens to become the century's major public health problem and poses enormous human and economic challenges in the U.S. and worldwide," said Dr. Nathan.
Dr. Nathan is the senior medical and scientific investigator for the project and chairs the GRADE Research Group. The director of the Coordinating Center, Dr. Lachin, is the senior biostatistician for the project and is responsible for the coordination of all study research activities. Together they will provide the scientific leadership for the project and oversee all study activities.
The study will address the challenges of type 2 diabetes in a randomized, clinical trial of 6,000 patients with recent onset of type 2 diabetes. The GRADE study will compare the effects of four glucose-lowering medications - the sulfonylurea glimepiride, DPP-4 inhibitor sitagliptin GLP-1 agonist liraglutide and basal insulin glargine, added to metformin - over about four years and track their success in combating the disease. Each of the drugs will be used in combination with metformin, the widely accepted first line medication for treatment of type 2 diabetes.
"For people with type 2 diabetes, this is a compelling need because numerous competing treatments are available," said Dr. Lachin. "While each agent was found to safely and effectively reduce blood glucose for relatively short periods such as six months to a year, type 2 diabetes will usually require continued treatment over a lifetime. GRADE'S primary objective is a direct comparison of the commonly used drugs over a more realistic period of time with regard to glucose-lowering, side-effects, tolerability, other effects and costs."
Glucose management is important in diabetes patients because sustained elevated levels of blood glucose can lead to extensive damage to the circulatory system which then can lead to a host of diabetic complications. Damage to the nerves can lead to amputations of the extremities, particularly feet; damage to the kidneys can lead to end stage renal disease requiring dialysis or transplantation; and damage to the eyes can lead to impaired vision or blindness.
"The goal of therapy should be to maintain a blood glucose level as close to the non-diabetes range as possible to prevent or slow the progression of these complications," said Dr. Lachin. "The principal study objective is to determine which of these therapies most effectively and safely reaches and maintains such near normal levels of blood glucose."
More than 40 participating clinical centers each plan to recruit at least 150 eligible patients who have consented to be randomly assigned to one of the four therapies under study. Funds from the grant to GW will be dispersed to these centers to support their activities in the GRADE study.
GW's Biostatistics Center will coordinate all research and operational activities at all sites for the study.
The initial steps of the project are to begin Oct. 1. The present grant supports the first five years of the project, with the opportunity for renewal for an additional three years. The total project duration is scheduled to be eight years.
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