827-P: 2022 Update on the BCG Clinical Trial Programs in Advanced Type 1 Diabetes

The bacillus Calmette-Guerin (BCG) vaccine was first introduced a century ago for tuberculosis prevention and is today being tested in double-blinded, randomized clinical trials for treatment of diverse forms of autoimmunity, including type 1 diabetes (T1D) and multiple sclerosis (MS) . At our institution, multiple clinical protocols are underway to test various aspects of BCG’s ability to lower HbA1c, reduce insulin requirements and change day-to-day fluctuations in blood sugars. Clinical trial subjects are in study groups including: 1) Long-term follow up of a Phase I study of BCG vaccination in longstanding T1D to study the durability of lowered HbA1c values after BCG treatment; 2) Randomized, double-blinded Phase II clinical trial testing the BCG vaccine in adults with longstanding T1D to demonstrate the reproducibility of BCG’s effects seen in the Phase I trial; 3) Radiologic study to quantify and identify through FDG-CAT scans the organs and organ systems that utilize more sugar after BCG treatment; 4) Study in adults with longstanding T1D to evaluate the effects of two doses of BCG compared to 6 doses of BCG over 5 years of observation; and 5) A soon-to-launch multi-center clinical trial of adolescents with > 2 years since T1D diagnosis to evaluate the potential benefits of BCG vaccination in this cohort. Basic science studies at our institution continue to show that, even in subjects with no pancreas reserve, the effects of BCG on blood sugar are mediated by the restoration of regulated sugar transport in the lymphoid system to corrected aerobic glycolysis. Patients are also being monitored by RNAseq, epigenetics, Treg cell numbers and signature gene expression to better define the mechanism of BCG’s effects. Global studies on the beneficial off-target effects of BCG on the immune system show that the impact of multi-dose vaccination in MS and T1D is seen with 2 years of follow-up and that the effects appear durable without further treatment in both MS and T1D to 5+ years.