A randomized controlled pilot trial of etanercept and alpha-1 antitrypsin to improve autologous islet engraftment

Abdel-Karim, Tasneem; Hodges, James S.; Pruett, Timothy L.; Ramanathan, Karthik; Hering, Bernhard J.; Dunn, Ty B.; Kirchner, Varvara A.; Beilman, Gregory J.; Bellin, Melena D.

doi:10.1016/j.pan.2022.11.006

Cited by 4 publications

(6 citation statements)

References 32 publications

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“…Although an AAT dose of 240 mg/kg was confirmed to be safe in animals 32 , 33 and patients 34 , a lower dose and more traditional dosing interval in this acute inflammatory condition proved ineffective 19 , 35 . A recently published trial with an AAT dose of 90 mg/kg similar to this study also did not have efficacy improvements 4 . Therefore, very much higher doses of AAT before surgery would be needed to try and overcome the acute neutrophilic effects following pancreatic resection.…”

Section: Discussionsupporting

confidence: 63%

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Alpha-1 Antitrypsin Augmentation Therapy in Chronic Pancreatitis Patients Undergoing Total Pancreatectomy and Islet Autotransplantation: A Randomized, Controlled Study

Wang,

Gou,

Nietert

et al. 2024

Cell Transplant

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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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Section: Discussionsupporting

confidence: 63%

“…Clinical trials using anti-inflammatory and other strategies have been conducted to improve the survival of autograft after transplantation 4 – 9 . Alpha-1 antitrypsin (AAT, also called alpha-1 proteinase inhibitor, A1PI) is a serine protease inhibitor that belongs to the serpin superfamily of proteins.…”

Section: Introductionmentioning

confidence: 99%

Alpha-1 Antitrypsin Augmentation Therapy in Chronic Pancreatitis Patients Undergoing Total Pancreatectomy and Islet Autotransplantation: A Randomized, Controlled Study

Wang,

Gou,

Nietert

et al. 2024

Cell Transplant

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“…The survival of islet autograft is the key and difficult point of TPIAT. Although researchers have made many attempts to improve the survival of islet autograft after TPIAT, such as autologous mesenchymal stem cell and islet co-transplantation, 101 etanercept, 102 carbon monoxide-saturated mediums (NCT02567240), α-1 antitrypsin (NCT02947087), hydroxychloroquine (NCT03283566), and reparixin (NCT01967888), there is currently no practical way to improve the survival of islet autograft.…”

Section: Surgical Strategymentioning

confidence: 99%

Management of chronic pancreatitis: recent advances and future prospects

Han,

Lv,

2024

Therap Adv Gastroenterol

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As a progressive fibroinflammatory disease, chronic pancreatitis (CP) often manifests as recurrent bouts of abdominal pain with or without complications, causing a heavy burden of health care. In recent years, some meaningful insights into the management of CP have been obtained from randomized controlled trials, systematic reviews, and meta-analyses, which were of great importance. Based on this research, it is shown that there are various treatments for CP. Therefore, it is of great importance to choose a suitable strategy for patients with CP individually. Relevant evidence on the management of CP was summarized in this review, including nutrition supplements, medication, endoscopy, surgery, exploration of novel therapies as well as evaluation and prediction of treatment response.

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“…14 Perioperative alpha one antitrypsin and interleukin 8 blockade do not improve insulin independence, but perioperative etanercept may improve transplanted islet engraftment. 15,16 Also, mesenchymal stem cell cotransplantation with islets has shown promise in decreasing insulin requirements and improving quality of life after TPIAT in pilot studies, with larger studies ongoing. 17…”

Section: The Future Of Total Pancreatectomy With Islet Autotransplant...mentioning

confidence: 99%

Update on Total Pancreatectomy With Islet Autotransplantation

Morgan

2023

The American Surgeon™

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A randomized controlled pilot trial of etanercept and alpha-1 antitrypsin to improve autologous islet engraftment

Cited by 4 publications

References 32 publications

Alpha-1 Antitrypsin Augmentation Therapy in Chronic Pancreatitis Patients Undergoing Total Pancreatectomy and Islet Autotransplantation: A Randomized, Controlled Study

Alpha-1 Antitrypsin Augmentation Therapy in Chronic Pancreatitis Patients Undergoing Total Pancreatectomy and Islet Autotransplantation: A Randomized, Controlled Study

Management of chronic pancreatitis: recent advances and future prospects

Update on Total Pancreatectomy With Islet Autotransplantation

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