drugset / Trial / NCT00505375
Intravenous CTLA4-lg Treatment in Recent Onset Type 1 Diabetes Mellitus
Phase 2
Completed
112 enrolled
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
American Diabetes Association · collabEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) · collabJuvenile Diabetes Research Foundation · collabNational Institute of Allergy and Infectious Diseases (NIAID) · collab
RandomizedParallel-groupTriple-blindTreatment
Summary
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.
Timeline
- Start
- 2008-02
- Primary completion
- 2012-05
- Completion
- 2012-05
Publications
- Background Bach JF. Insulin-dependent diabetes mellitus as an autoimmune disease. Endocr Rev. 1994 Aug;15(4):516-42. doi: 10.1210/edrv-15-4-516.
- Background Bretscher PA. A two-step, two-signal model for the primary activation of precursor helper T cells. Proc Natl Acad Sci U S A. 1999 Jan 5;96(1):185-90. doi: 10.1073/pnas.96.1.185.
- Background Alegre ML, Frauwirth KA, Thompson CB. T-cell regulation by CD28 and CTLA-4. Nat Rev Immunol. 2001 Dec;1(3):220-8. doi: 10.1038/35105024.
- Background Lenschow DJ, Zeng Y, Thistlethwaite JR, Montag A, Brady W, Gibson MG, Linsley PS, Bluestone JA. Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA4lg. Science. 1992 Aug 7;257(5071):789-92. doi: 10.1126/science.1323143.
- Background Abrams JR, Lebwohl MG, Guzzo CA, Jegasothy BV, Goldfarb MT, Goffe BS, Menter A, Lowe NJ, Krueger G, Brown MJ, Weiner RS, Birkhofer MJ, Warner GL, Berry KK, Linsley PS, Krueger JG, Ochs HD, Kelley SL, Kang S. CTLA4Ig-mediated blockade of T-cell costimulation in patients with psoriasis vulgaris. J Clin Invest. 1999 May;103(9):1243-52. doi: 10.1172/JCI5857.
- Background Abrams JR, Kelley SL, Hayes E, Kikuchi T, Brown MJ, Kang S, Lebwohl MG, Guzzo CA, Jegasothy BV, Linsley PS, Krueger JG. Blockade of T lymphocyte costimulation with cytotoxic T lymphocyte-associated antigen 4-immunoglobulin (CTLA4Ig) reverses the cellular pathology of psoriatic plaques, including the activation of keratinocytes, dendritic cells, and endothelial cells. J Exp Med. 2000 Sep 4;192(5):681-94. doi: 10.1084/jem.192.5.681.
- Background Moreland LW, Alten R, Van den Bosch F, Appelboom T, Leon M, Emery P, Cohen S, Luggen M, Shergy W, Nuamah I, Becker JC. Costimulatory blockade in patients with rheumatoid arthritis: a pilot, dose-finding, double-blind, placebo-controlled clinical trial evaluating CTLA-4Ig and LEA29Y eighty-five days after the first infusion. Arthritis Rheum. 2002 Jun;46(6):1470-9. doi: 10.1002/art.10294.
- Results Orban T, Bundy B, Becker DJ, DiMeglio LA, Gitelman SE, Goland R, Gottlieb PA, Greenbaum CJ, Marks JB, Monzavi R, Moran A, Raskin P, Rodriguez H, Russell WE, Schatz D, Wherrett D, Wilson DM, Krischer JP, Skyler JS; Type 1 Diabetes TrialNet Abatacept Study Group. Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial. Lancet. 2011 Jul 30;378(9789):412-9. doi: 10.1016/S0140-6736(11)60886-6. Epub 2011 Jun 28.
- Orban T, Beam CA, Xu P, Moore K, Jiang Q, Deng J, Muller S, Gottlieb P, Spain L, Peakman M; Type 1 Diabetes TrialNet Abatacept Study Group. Reduction in CD4 central memory T-cell subset in costimulation modulator abatacept-treated patients with recent-onset type 1 diabetes is associated with slower C-peptide decline. Diabetes. 2014 Oct;63(10):3449-57. doi: 10.2337/db14-0047. Epub 2014 May 16.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Abatacept | Other / unclassified | 10 mg/kg | Intravenous |