Intravenous CTLA4-lg Treatment in Recent Onset Type 1 Diabetes Mellitus
The purpose of this study is to determine whether treatment with CTLA4-Ig (Abatacept) in individuals with new onset T1DM will improve insulin secretion (C-peptide production) compared to placebo.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||Effects of CTLA-4 Ig (Abatacept) On The Progression of Type 1 Diabetes In New Onset Subjects|
- Insulin production (C-peptide secretion) [ Time Frame: 2 years of follow up ] [ Designated as safety issue: No ]
- HbA1c [ Time Frame: 2 years of follow up ] [ Designated as safety issue: No ]
- Number and severity of hypoglycemic events [ Time Frame: 2 years of follow up ] [ Designated as safety issue: No ]
- Immunologic outcomes [ Time Frame: 2 years of follow up ] [ Designated as safety issue: No ]
|Study Start Date:||February 2008|
|Estimated Study Completion Date:||June 2013|
|Estimated Primary Completion Date:||February 2012 (Final data collection date for primary outcome measure)|
Intravenous infusions of CTLA-4 Ig
Drug: CTLA-4 Ig
Intravenous infusion of 10 mg/kg of CTLA-4 Ig every other week for the first two doses and then every 28 days for a total of 27 doses
Other Name: Abatacept
Placebo Comparator: 2
Intravenous infusions of placebo
Intravenous infusions of placebo every other week for the first two doses and then every 28 days for a total of 27 doses
Type 1 diabetes mellitus (T1DM) is a T-cell mediated autoimmune disease in which insulin-producing beta cells are completely or near completely destroyed resulting in life-long dependence on exogenous insulin.
CTLA4-Ig (Abatacept) inhibits a crucial stimulatory pathway in the activation of T cells. By this mechanism, the drug is thought to arrest or slow the T cell mediated autoimmune destruction of beta-cells and preserve their function. At the time of clinical onset of T1DM, a significant amount of insulin producing beta cells are destroyed, but as many as 10-20% are still capable of insulin production. By using CTLA4-Ig close to the onset of T1DM, we hope to arrest or slow down the autoimmune destruction of these beta-cells and extend the endogenous insulin production. CTLA4-Ig regulates T cell function but does not deplete T cells. Therefore, its safety profile appears to be better than other immunosuppressive agents.
Eligible participants will be randomized to the experimental or control groups. The experimental group will receive intravenous infusions of CTLA-4 Ig. The first infusion will occur at the time of randomization, followed by another infusion 2 and 4 weeks later. Subsequent infusions will be given monthly for two years during the treatment phase of the study. There is a total of 27 infusions during the treatment phase of the study.
Participants in the control group will receive intravenous infusions of placebo according to the same schedule outlined above.
Both groups will receive standard intensive diabetes treatment with insulin and dietary management.
All participants randomized into the study will be seen at study site monthly for 24 months and then every 6 months for up to an additional 2 years. Participants will undergo assessments of their insulin production, immunologic status, overall health and well being and diabetes care.
|United States, California|
|Childrens Hospital Los Angeles|
|Los Angeles, California, United States, 90027|
|University of California - San Francisco|
|San Francisco, California, United States, 94143|
|Stanford, California, United States, 94305|
|United States, Colorado|
|The Barbara Davis Center for Childhood Diabetes|
|Aurora, Colorado, United States, 80045|
|United States, Florida|
|University of Florida|
|Gainesville, Florida, United States, 32610-0296|
|University of Miami|
|Miami, Florida, United States, 33136|
|United States, Massachusetts|
|Joslin Diabetes Center|
|Boston, Massachusetts, United States, 02215|
|United States, Minnesota|
|University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|United States, New York|
|Columbia University, Naomi Berrie Diabetes Center|
|New York, New York, United States, 10032|
|United States, Pennsylvania|
|University of Pittsburgh, Children's Hospital of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15213|
|United States, Texas|
|University of Texas, Southwestern Medical School|
|Dallas, Texas, United States, 75235-8858|
|United States, Washington|
|Benaroya Research Institute|
|Seattle, Washington, United States, 98101|
|The Hospital for Sick Children|
|Toronto, Ontario, Canada, M5G-1X8|
|Principal Investigator:||Tihamer Orban, MD||Joslin Diabetes Center|
|Study Chair:||Jay Skyler, MD||University of Miami|