接受全胰腺切除术和胰岛自体移植的慢性胰腺炎患者的 Alpha-1 抗胰蛋白酶增强疗法:随机对照研究

IF 3.2 4区 医学 Q3 CELL & TISSUE ENGINEERING Cell Transplantation Pub Date : 2024-04-25 DOI:10.1177/09636897241243014
Hongjun Wang, Wenyu Gou, Paul J. Nietert, Jason Hirsch, Jingjing Wang, Ahmed Allawi, Abd S. Mortadha, Kelsey Cook, Morgan Overstreet, Hua Wei, David Adams, William P. Lancaster, Katherine A. Morgan, Charlie Strange
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引用次数: 0

摘要

在胰岛移植围手术期,应激引起的胰岛移植物丢失会降低胰岛移植的疗效。在这项前瞻性、随机、双盲临床试验中,我们对接受全胰腺切除术和胰岛自体移植术(TP-IAT)的慢性胰腺炎(CP)患者在手术前开始输注 60 毫克/千克人α-1 抗胰蛋白酶(AAT)或安慰剂(每周四次)的安全性和有效性进行了评估。TP-IAT术后对受试者进行12个月的随访。AAT的剂量是安全的,因为两组受试者的不良反应类型和严重程度没有差异。AAT组在移植前的耗氧率较高,而在输注胰岛素15分钟后,AAT组的血清C肽(胰岛素死亡的指标)较低,这些都是治疗效果的生化信号。根据使用修正的意向治疗分析的统计分析计划得出的结果显示,TP-IAT 移植后 12 个月进行混合膳食耐受试验后,C 肽曲线下面积(AUC)没有差异。次要和探索性结果也无差异。虽然在这项研究中,AAT疗法没有改善C肽的AUC,但AAT疗法对CP患者是安全的,而且在这种具有挑战性的疾病的最佳临床试验设计方面积累了经验。
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Alpha-1 Antitrypsin Augmentation Therapy in Chronic Pancreatitis Patients Undergoing Total Pancreatectomy and Islet Autotransplantation: A Randomized, Controlled Study
Stress-induced islet graft loss during the peri-transplantation period reduces the efficacy of islet transplantation. In this prospective, randomized, double-blind clinical trial, we evaluated the safety and efficacy of 60 mg/kg human alpha-1 antitrypsin (AAT) or placebo infusion weekly for four doses beginning before surgery in chronic pancreatitis (CP) patients undergoing total pancreatectomy and islet autotransplantation (TP-IAT). Subjects were followed for 12 months post-TP-IAT. The dose of AAT was safe, as there was no difference in the types and severity of adverse events in participants from both groups. There were some biochemical signals of treatment effect with a higher oxygen consumption rate in AAT islets before transplantation and a lower serum C-peptide (an indicator of islet death) in the AAT group at 15 min after islet infusion. Findings per the statistical analysis plan using a modified intention to treat analysis showed no difference in the C-peptide area under the curve (AUC) following a mixed meal tolerance test at 12 months post-TP-IAT. There was no difference in the secondary and exploratory outcomes. Although AAT therapy did not show improvement in C-peptide AUC in this study, AAT therapy is safe in CP patients and there are experiences gained on optimal clinical trial design in this challenging disease.
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来源期刊
Cell Transplantation
Cell Transplantation 生物-细胞与组织工程
CiteScore
6.00
自引率
3.00%
发文量
97
审稿时长
6 months
期刊介绍: Cell Transplantation, The Regenerative Medicine Journal is an open access, peer reviewed journal that is published 12 times annually. Cell Transplantation is a multi-disciplinary forum for publication of articles on cell transplantation and its applications to human diseases. Articles focus on a myriad of topics including the physiological, medical, pre-clinical, tissue engineering, stem cell, and device-oriented aspects of the nervous, endocrine, cardiovascular, and endothelial systems, as well as genetically engineered cells. Cell Transplantation also reports on relevant technological advances, clinical studies, and regulatory considerations related to the implantation of cells into the body in order to provide complete coverage of the field.
期刊最新文献
ASNTR 2024 Abstracts Role of Hedgehog Signaling Pathways in Multipotent Mesenchymal Stem Cells Differentiation Hematopoietic Stem Cell Transplantation in Sickle Cell Disease: A Multidimentional Review Alpha-1 Antitrypsin Augmentation Therapy in Chronic Pancreatitis Patients Undergoing Total Pancreatectomy and Islet Autotransplantation: A Randomized, Controlled Study Persistent Cytopenia After CD19 CAR T Therapy in Relapsed/Refractory DLBCL Patients Could Be a Predictor of Efficacy and Side Effects
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