Journal
AMERICAN JOURNAL OF TRANSPLANTATION
Volume 21, Issue 11, Pages 3714-3724Publisher
WILEY
DOI: 10.1111/ajt.16695
Keywords
clinical trial; cytokines; cytokine receptors; innate immunity; insulin; C-peptide; islets of Langerhans; pancreatitis; TPIAT; total pancreatectomy
Categories
Funding
- Dompe farmaceutici
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The use of reparixin for islet autotransplantation in patients undergoing total pancreatectomy did not significantly improve outcomes. Inhibiting the CXCL8 pathway alone may not be sufficient to prevent islet damage in transplantation procedures. This first multicenter clinical trial in TPIAT shows potential for future collaborations.
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 A(1c) (HbA(1c)), 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 HbA(1c) <= 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.
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