{Reference Type}: Randomized Controlled Trial
{Title}: A randomized controlled pilot trial of etanercept and alpha-1 antitrypsin to improve autologous islet engraftment.
{Author}: Abdel-Karim TR;Hodges JS;Pruett TL;Ramanathan KV;Hering BJ;Dunn TB;Kirchner VA;Beilman GJ;Bellin MD;
{Journal}: Pancreatology
{Volume}: 23
{Issue}: 1
{Year}: Jan 2023
{Factor}: 3.977
{DOI}: 10.1016/j.pan.2022.11.006
{Abstract}: <B>BACKGROUND: </B>In total pancreatectomy with islet auto-transplantation, successful diabetes outcomes are limited by islet loss from the instant blood mediated inflammatory response. We hypothesized that blockade of the inflammatory response with either etanercept or alpha-1-antitrypsin would improve islet function and insulin independence.<BR><B>METHODS: </B>We randomized 43 participants to receive A1AT (90 mg/kg x 6 doses, n = 13), or etanercept (50 mg then 25 mg x 5 doses, n = 14), or standard care (n = 16), aiming to reduce detrimental effects of innate inflammation on early islet survival. Islet graft function was assessed using mixed meal tolerance testing, intravenous glucose tolerance testing, glucose-potentiated arginine-induced insulin secretion studies, HbA1c, and insulin dose 3 months and 1 year post-TPIAT.<BR><B>RESULTS: </B>We observed the most robust acute insulin response (AIRglu) and acute C-peptide response to glucose (ACRglu) at 3 months after TPIAT in the etanercept-treated group (p ≤ 0.02), but no differences in other efficacy measures. The groups did not differ overall at 1 year but when adjusted by sex, there was a trend towards a sex-specific treatment effect in females (AIRglu p = 0.05, ACRglu p = 0.06), with insulin secretion measures highest in A1AT-treated females.<BR><B>CONCLUSIONS: </B>Our randomized trial supports a potential role for etanercept in optimizing early islet engraftment but it is unclear whether this benefit is sustained. Further studies are needed to evaluate possible sex-specific responses to either treatment.<BR><B>UNASSIGNED: </B>This study was performed under an Investigational New Drug Application (IND #119828) from the Food and Drug Administration and was registered on clinicaltrials.gov (NCT#02713997).