eligibility_summary
Adults 18–70 with T1D (onset <45, insulin ≥5y or age+duration ≥28), absent stimulated C‑peptide, on intensive insulin therapy, ≥2 severe hypos in 12 mo with impaired awareness, can use Tandem X2 Control‑IQ, contraception. Prior kidney transplant on immunosuppression allowed. Exclude: BMI>30 or ≤50kg, insulin >1u/kg/d or <15U, HbA1c>10%, proliferative retinopathy, HTN>180/100, eGFR<50 or macroalbuminuria, HLA sensitization, infections (HBV/HCV/HIV/TB, EBV IgG−), malignancy, cytopenias, coagulopathy/anticoag, severe cardiac/liver disease, pancreatitis, prior islet tx, nonadherence, anti‑IgA/IgA deficiency.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
manual_review_required
ai_summary
Phase 1, parallel-group trial in brittle type 1 diabetes tests islet transplantation plus one of two adjunct cellular therapies: 1) Autologous regulatory T cells (Tregs, biological cell therapy) purified by apheresis and reinfused to suppress alloimmunity via CTLA-4 signaling, IL-2 consumption, IL-10/TGF-beta production, and inhibition of effector T cells and antigen-presenting cells, 2) Donor-derived vertebral bone marrow (VBM, allogeneic HSC/immune cell therapy) from the islet donor to promote mixed chimerism and central/peripheral tolerance to donor islets. All participants also receive: ATG (polyclonal T-cell–depleting antibody), belatacept (CTLA4-Ig costimulation blocker of CD80/86–CD28), tacrolimus ER (calcineurin/NFAT inhibitor), and mycophenolate mofetil (IMPDH inhibitor). Targets: effector T cells, APCs, CD28 costimulation, calcineurin signaling, lymphocyte purine synthesis, and tolerance pathways via Tregs/HSCs.