OBJECTIVE: A pilot study suggested that combination therapy with low-dose anti-thymocyte globulin (ATG) and pegylated granulocyte colony-stimulating factor (GCSF) preserves C-peptide in established type 1 diabetes (T1D) (duration 4 months to 2 years). We hypothesized that 1) low-dose ATG/GCSF or 2) low-dose ATG alone would slow the decline of β-cell function in patients with new-onset T1D (duration <100 days). RESEARCH DESIGN AND METHODS: A three-arm, randomized, double-masked, placebo-controlled trial was performed by the Type 1 Diabetes TrialNet Study Group in89 subjects: 29 subjects randomized to ATG (2.5 mg/kg intravenously) followed by pegylated GCSF (6 mg subcutaneously every 2 weeks for 6 doses), 29 to ATG alone (2.5 mg/kg), and 31 to placebo. The primary end point was mean area under the curve (AUC) C-peptide during a 2-h mixed-meal tolerance test 1 year after initiation of therapy. Significance was defined as one-sided P value < 0.025. RESULTS: The 1-year mean AUC C-peptide was significantly higher in subjects treated with ATG (0.646 nmol/L) versus placebo (0.406 nmol/L) (P = 0.0003) but not in those treated with ATG/GCSF (0.528 nmol/L) versus placebo (P = 0.031). HbA1c was significantly reduced at 1 year in subjects treated with ATG and ATG/GCSF, P = 0.002 and 0.011, respectively. CONCLUSIONS: Low-dose ATG slowed decline of C-peptide and reduced HbA1c in new-onset T1D. Addition of GCSF did not enhance C-peptide preservation afforded by low-dose ATG. Futurestudies should be considered to determine wheth erlow-dose ATG aloneorin combination with other agents may prevent or delay the onset of the disease.
Bibliographical noteFunding Information:
Funding. The sponsor of the trial was the Type 1 Diabetes TrialNet Study Group. The Type 1 Diabetes TrialNet Study Group is a clinical trials network funded by the National Institutes of Health (NIH) through the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the cooperative agreements U01 DK061010, U01 DK061034, U01 DK061042, U01 DK061058, U01 DK085465, U01 DK085461, UC4 DK085466, U01 DK085476, U01 DK085499, U01 DK085509, U01 DK097835, U01 DK103266, U01 DK103282, U01 DK106984, U01 DK107014, and UC4 DK106993; the National Center for Research Resources through Clinical Translational Science Awards UL1TR001085, UL1TR001427, UL1TR001863, UL1TR001082, UL1TR000114, UL1TR001857, and UL1TR000445; JDRF; and the American Diabetes Association. Additional funding was provided by The Leona M. and Harry B. Helmsley Charitable Trust (2015PG-T1D032) and the McJunkin Family Charitable Foundation. Sanofi provided Thymo-globulin (ATG), Amgen provided Neulasta (GCSF) and placebo, and Roche Diabetes Care provided diabetes management supplies for the study.