Subcutaneous injection consisting of alum-formulated glutamate decarboxylase (GAD-Alum) is considered safe for prediabetic children, despite its inability to have a significant impact on the time to type 1 diabetes diagnosis, according to findings from a double-blind placebo-controlled clinical trial published in Pediatric Diabetes.
A total of 50 nondiabetic children between age 4 and 17.9 with autoantibodies to glutamate decarboxylase (GADA) were randomly assigned 1:1 to either 2 injections of 20 μg GAD-Alum (n=25) or placebo (n=25). The primary outcome consisted of safety as assessed by adverse events, chemistry, hematology, thyroid function, celiac autoimmunity, and titers of islet autoantibodies. In addition, efficacy, defined as the cumulative incidence of diabetes over 5 years, was assessed.
The use of GAD-Alum injections did not have a significant impact on any safety parameter; however, titers of GADA did demonstrate a significant increase (P =.001). Transient injection site reactions were considered mild or moderate and occurred equally in patients receiving GAD-Alum and placebo (P =.771). There were 878 adverse events reported at either 5-year follow-up or type 1 diabetes diagnosis. Of these, a total of 4 adverse events were considered serious but none were deemed related to the study drug.
In participants with normal and impaired glucose metabolism, treatment did not significantly affect time to diabetes diagnosis (P =.359 and P =.376, respectively). Also, treatment did not appear to directly affect the time to clinical diagnosis of diabetes (hazard ratio 0.77, P =.574) in the study population.
The ability to generalize these findings is limited since this was a single-center study with a small patient population. According to the investigators, high levels of insulinoma-associated protein 2 or specific variants of zinc transporter 8 autoantibody may have also affected the intervention and the time to type 1 diabetes diagnosis.
Overall, the findings indicate that GADA (GAD65) can prove useful “for prevention studies earlier in the autoimmune process…[and] to guide future studies of autoantigen-specific therapy with GAD65.”
Elding Larsson H, Lundgren M, Jonsdottir B, Cuthbertson D, Krischer J; DiAPREV-IT Study Group. Safety and efficacy of autoantigen-specific therapy with 2 doses of alum-formulated glutamate decarboxylase in children with multiple islet autoantibodies and risk for type 1 diabetes: a randomized clinical trial [published online November 24, 2017]. Pediatr Diabetes. doi:10.1111/pedi.12611