Release Date: March 11, 2011
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) is announcing the opportunity to participate as a clinical site in a multicenter trial, the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) study. The overarching goal of this trial is to understand the relative effectiveness of different medications in combination with metformin, and whether introducing them sequentially (i.e. the traditional treatment strategy) or initially in combination is most effective in maintaining glycemic goals over time. This study will include patients with type 2 diabetes of less than 3 years in duration.
The epidemic of type 2 diabetes that has affected the U.S. and other populations in the last half of the 20th and first part of the 21st centuries threatens to become the major public health problem of this century. The most recent estimates in the U.S. include a prevalence of approximately 24.5 million persons with type 2 diabetes, with an incidence of 1.8 million new cases per year. One of the major challenges for practitioners is to choose the best means for achieving from the outset and then maintaining an appropriate level of glycemic control over time. Unfortunately, there is a dearth of head-to-head comparator studies of different glucose-lowering medications, either alone or in combinations. Moreover, only a few studies have examined the durable effects of interventions on glycemic control. Given the importance of achieving and maintaining adequate glycemic control over time, it is critical to understand the relative effectiveness of the different medications and their combinations, and whether introducing them sequentially, the traditional treatment strategy, or initially in combination is most effective in maintaining glycemic goals over time.
This trial will compare:
1. The relative benefits of five anti-diabetic medications, with different glucose lowering mechanisms, when used in conjunction with metformin, and
2. Two treatment strategies: the introduction of combination therapy early in the course of diabetes care (early combination therapy) and sequential therapy to determine which strategy will provide improved glycemic control over time.
The trial will be conducted at clinical sites throughout the United States of America with expertise in conduct of clinical trials in type 2 diabetes. These centers will enroll 7,500 patients with recently diagnosed type 2 diabetes over approximately 3 years. The average duration of follow-up is anticipated to be approximately 4 years. The Study Chair for this clinical trial is David Nathan, MD from Massachusetts General Hospital, and the Coordinating Center will be the George Washington University Biostatistics Center.
Additional information about the study can be found at: http://www2.bsc.gwu.edu/bsc/grade.html
This Notice is being provided to alert potential clinical investigators to the opportunity to participate and to provide sufficient time to respond completely with the information required to apply for consideration.
In supporting this trial, the NIDDK wishes to provide important currently unavailable data on the comparative efficacy, safety, tolerability, and effects on other clinically relevant factors of currently available medications to treat diabetes that will help inform physicians when making treatment decisions. Additionally the results of this trial may inform organizations in the development of policy and treatment guidelines.
Planning for this trial has begun under a cooperative
agreement, funded under PAR-10-197 https://grants.nih.gov/grants/guide/pa-files/PAR-10-197.html which invited applications for investigator-initiated,
multi-center clinical studies exclusively through a two-part process that
includes an implementation planning (U34) grant. Planning and executive
committees have been working to finalize the protocol and develop the manual of
operations and other documents needed to implement the trial. The GRADE study
is soliciting clinical investigators to participate in the conduct of the
trial. After planning for this trial has been completed (including selection
of clinical sites), the principal investigator and coordinating center will
apply for a U01 under PAR-08-058 to support implementation of the clinical
trial. https://grants.nih.gov/grants/guide/pa-files/PAR-08-058.html.
This Notice encourages investigators with expertise in the conduct of clinical trials in type 2 diabetes to respond to the "Opportunity to Participate; Request for Support" issued by the George Washington University Biostatistics Center: http://www2.bsc.gwu.edu/bsc/gradesite.html.
Requests to participate may be submitted by institutions in the United States. Principal investigators should be experienced in the conduct of diabetes trials and have the ability to recruit over a 3 year period a minimum of 150 subjects with a known duration of type 2 diabetes of less than 3 years.
Please direct all inquiries to:
Myrlene Staten, M.D.
Division of Diabetes, Endocrinology and Metabolism
National Institute of Diabetes and Digestive and Kidney
Diseases, NIH
6707 Democracy Boulevard, Room 6107
Bethesda, MD 20892-5458
Phone: 301-402-7886
Fax: 301-480-3503
Email: [email protected]
and Human Services (HHS)
