A randomized controlled pilot trial of etanercept and alpha-1 antitrypsin to improve autologous islet engraftment

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4 Scopus citations

Abstract

Background: 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. Methods: 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. Results: 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. Conclusion: 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. Clinical trial notation: 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).

Original languageEnglish (US)
Pages (from-to)57-64
Number of pages8
JournalPancreatology
Volume23
Issue number1
DOIs
StatePublished - Jan 2023

Bibliographical note

Funding Information:
This study was funded by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases grant number R01DK109914 (PI Bellin). This research was supported by the National Institutes of Health's National Center for Advancing Translational Sciences , grant UL1TR002494 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health's National Center for Advancing Translational Sciences.

Publisher Copyright:
© 2022 IAP and EPC

Keywords

  • Chronic pancreatitis
  • Cytokines
  • Diabetes
  • Islet autotransplantation
  • TPIAT

PubMed: MeSH publication types

  • Journal Article
  • Randomized Controlled Trial

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