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.
CONCLUSIONS: 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.
UNASSIGNED: 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).
方法:我们随机分配43名参与者接受A1AT(90mg/kgx6剂,n=13),或依那西普(50毫克,然后25毫克×5剂量,n=14),或标准护理(n=16),旨在减少先天性炎症对早期胰岛存活的有害影响。使用混合膳食耐受性测试评估胰岛移植物功能,静脉葡萄糖耐量试验,葡萄糖增强精氨酸诱导的胰岛素分泌研究,HbA1c,TPIAT后3个月和1年的胰岛素剂量。
结果:我们观察到依那西普治疗组在TPIAT治疗后3个月最强烈的急性胰岛素反应(AIRglu)和急性C肽对葡萄糖的反应(ACRglu),但其他疗效指标无差异。两组在1年时总体上没有差异,但按性别调整后,女性有性别特异性治疗效果的趋势(AIRglup=0.05,ACRglup=0.06),在A1AT治疗的女性中,胰岛素分泌指标最高。
结论:我们的随机试验支持依那西普在优化早期胰岛植入方面的潜在作用,但不清楚这种益处是否持续。需要进一步的研究来评估对这两种治疗可能的性别特异性反应。
UNASSIGNED:本研究是根据食品和药物管理局的研究新药申请(IND#119828)进行的,并在clinicaltrials.gov(NCT#02713997)上注册。