Alpha-1 Antitrypsin (AAT) Enhances Islet Autograft Survival in Patients With Chronic Pancreatitis

Alpha-1 Antitrypsin (AAT) Enhances Islet Autograft Survival

Primary objective: To describe and compare the safety and efficacy of treatment with AAT in chronic pancreatitis patients who undergo total pancreatectomy and islet autotransplantation (TP-IAT).

Study Overview

• Status: Completed
• Conditions: Chronic Pancreatitis
• Intervention / Treatment: Drug: Prolastin-C; Drug: Placebo

Detailed Description

The goal of this study is to assess whether infusion of Prolastin-C during peri-transplant period can enhance islet autograft survival and function in chronic pancreatitis patients who have total pancreatectomy and islet autotransplantation. This is a prospective, controlled, double-blind study. The primary endpoint will be area under the curve for the serum C-peptide level during the first 4 hours of an mixed meal tolerance test (MMTT), normalized by the number of islet equivalents (IEQ)/kg at day 365±14 after the transplant.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients scheduled for total pancreatectomy and islet auto-transplantation
• Age > 18 years
• Diabetes free before surgery

Exclusion Criteria:

• Patients who are under immunosuppression
• Patients who have had Puestow or Frey pancreatic surgery
• Patients who have Immunoglobulin A (IgA) deficiency, known antibodies against IgA, or individuals with a history of severe immediate hypersensitivity reactions, including anaphylaxis to Alpha1-proteinase inhibitor products (allergic to AAT)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Prolastin-C; Subjects will be given Prolastin-C intravenously at 60mg/kg weekly for 4 weeks.	Drug: Prolastin-C; Patients will receive Prolastin-C at 60mg/kg on day 0, 7, 14, and 21 days of transplantation; Other Names: AAT
Placebo Comparator: Placebo; Subjects will be given Saline weekly for 4 weeks.	Drug: Placebo; Patients will receive saline on day 0, 7, 14, and 21 days of transplantation; Other Names: Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Islet Graft Function	Islet graft function will be measured by 4 hour mixed meal tolerance test (MMTT) at 365 days post transplantation. Specific measurement is the C-peptide area under the curve (AUC)	365 days

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Hongjun Wang, Ph.D, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2017
• Primary Completion (Actual): November 13, 2021
• Study Completion (Actual): November 13, 2022

Study Registration Dates

• First Submitted: October 18, 2016
• First Submitted That Met QC Criteria: October 25, 2016
• First Posted (Estimated): October 27, 2016

Study Record Updates

• Last Update Posted (Actual): June 29, 2023
• Last Update Submitted That Met QC Criteria: June 16, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Islet autotransplantation; Alpha1 anti trypsin
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Liver Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Subcutaneous Emphysema; Emphysema; Chronic Disease; Alpha 1-Antitrypsin Deficiency; Pancreatitis; Pancreatitis, Chronic; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Trypsin Inhibitors; Alpha 1-Antitrypsin
• Other Study ID Numbers: Pro00053906; 5R01DK105183 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified dataset available for sharing with researchers
• IPD Sharing Time Frame: Available 01MAR2023 indefinitely
• IPD Sharing Access Criteria: email to Wangho@musc.edu
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR