The purpose of this study is to identify early immune markers associated with response to treatment with abatacept in individuals with Type 1 diabetes (T1D). In this open label mechanistic study, participants who were recently diagnosed with T1D (males or females, ages 6-45 and \<7months from T1D diagnosis) will be treated with a short-course of abatacept (weekly subcutaneous injections for 3 months). Participants will undergo baseline and repeated mixed meal tolerance testing (MMTT) to assess disease progression and blood samples will be obtained at frequent intervals to measure changes in immune markers.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
60
Abatacept will be administered by subcutaneous injections weekly for 3 months. Dosing is according to body weight at screening visit and will be administered as follows: up to 25 kg receive 50 mg (0.4 mL); 25 to \<50 kg receive 87.5 mg (0.7 mL), and \> 50 kg receive 125 mg (1.0 mL) per dose.
Benaroya Research Institute
Seattle, Washington, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Change in insulin antibody titers (NIDDK units/mL)
Insulin antibody titers
Time frame: 0 to 2 weeks
Change in frequency of B cells within total PBMC (%)
% of B cells
Time frame: 0 to 2 weeks
Change in inflammatory Index by serum transcriptional exposure assay (composite score)
Inflammatory Index (359). This is an inflammatory index based on transcription of 359 probe sets (I.I.359) calculated by dividing the average signal intensity of the 103 probe sets generally annotated as 'inflammatory' by the average signal intensity of the 256 probe sets generally annotated as 'regulatory'
Time frame: 0 to 2 weeks
Change in B-cell transcriptional module (CD19.mod) (composite score)
CD19 mod is composite score of B cell transcripts.
Time frame: 0 to 2 weeks
Change in islet-specific exhausted CD8 T cells (%)
% of CD8+ T cells (CD8+PD-1+KLRG1+CD57-)
Time frame: 0 to 2 weeks
Change in EOMES CD8 whole blood gene expression signature (composite score)
Gene transcript score for EOMES module
Time frame: 0 to 2 weeks
Change in frequency of TfH within total CD4 T cells (%)
% of TfH cells within CD4+ T cells
Time frame: 0 to 2 weeks
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