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
{"title":"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","authors":"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","doi":"10.1177/09636897241243014","DOIUrl":null,"url":null,"abstract":"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.","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"22 1","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Alpha-1 Antitrypsin Augmentation Therapy in Chronic Pancreatitis Patients Undergoing Total Pancreatectomy and Islet Autotransplantation: A Randomized, Controlled Study\",\"authors\":\"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\",\"doi\":\"10.1177/09636897241243014\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"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.\",\"PeriodicalId\":9721,\"journal\":{\"name\":\"Cell Transplantation\",\"volume\":\"22 1\",\"pages\":\"\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-04-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell Transplantation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/09636897241243014\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CELL & TISSUE ENGINEERING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Transplantation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/09636897241243014","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
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.
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.