Targeting CXCR1/2 in the first multicenter, double-blinded, randomized trial in autologous islet transplant recipients

Piotr Witkowski, Martin Wijkstrom, Piotr J. Bachul, Katherine A. Morgan, Marlon Levy, Nicholas Onaca, Sushela S. Chaidarun, Timothy Gardner, A. M.James Shapiro, Andrew Posselt, Syed A. Ahmad, Luisa Daffonchio, Pier A. Ruffini, Melena D. Bellin

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Several cytokines and chemokines are elevated after islet infusion in patients undergoing total pancreatectomy with islet autotransplantation (TPIAT), including CXCL8 (also known as interleukin-8), leading to islet loss. We investigated whether use of reparixin for blockade of the CXCL8 pathway would improve islet engraftment and insulin independence after TPIAT. Adults without diabetes scheduled for TPIAT at nine academic centers were randomized to a continuous infusion of reparixin or placebo (double-blinded) for 7 days in the peri-transplant period. Efficacy measures included insulin independence (primary), insulin dose, hemoglobin A1c (HbA1c), and mixed meal tolerance testing. The intent-to-treat population included 102 participants (age 39.5 ± 12.2 years, 69% female), n = 50 reparixin-treated, n = 52 placebo-treated. The proportion insulin-independent at Day 365 was similar in reparixin and placebo: 20% vs. 21% (p =.542). Twenty-seven of 42 (64.3%) in the reparixin group and 28/45 (62.2%) in the placebo group maintained HbA1c ≤6.5% (p =.842, Day 365). Area under the curve C-peptide from mixed meal testing was similar between groups, as were adverse events. In conclusion, reparixin infusion did not improve diabetes outcomes. CXCL8 inhibition alone may be insufficient to prevent islet damage from innate inflammation in islet autotransplantation. This first multicenter clinical trial in TPIAT highlights the potential for future multicenter collaborations.

Original languageEnglish (US)
Pages (from-to)3714-3724
Number of pages11
JournalAmerican Journal of Transplantation
Volume21
Issue number11
Early online dateApr 25 2021
DOIs
StatePublished - Nov 2021

Bibliographical note

Publisher Copyright:
© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons

Keywords

  • TPIAT
  • clinical trial
  • cytokines / cytokine receptors
  • innate immunity
  • insulin / C-peptide
  • islets of Langerhans
  • pancreatitis
  • total pancreatectomy

Fingerprint

Dive into the research topics of 'Targeting CXCR1/2 in the first multicenter, double-blinded, randomized trial in autologous islet transplant recipients'. Together they form a unique fingerprint.

Cite this