Calcineurin Inhibitor-free, Steroid-free Immunosuppressive Regimen in Simultaneous Islet-Kidney Transplantation for Uremic Type 1 Diabetic Patients
Summary
The investigators hypothesize that a calcineurin inhibitor-free, steroid-free, co-stimulatory blockade-based immunosuppressive regimen, in combination with a GLP-1 agonist, will reduce the islet mass required to achieve and sustain insulin independence following simultaneous islet-kidney transplantation.
Description
This is a single center, open-label, non-randomized, prospective, pilot study of 8 Type 1 diabetic/uremic patients, ages 18-60 undergoing simultaneous islet-kidney transplantation. Study to include both male and/or female subjects.
We hypothesize that a calcineurin inhibitor-free, steroid-free, co-stimulatory blockade-based immunosuppressive regimen, in combination with a GLP-1 agonist, will reduce the islet mass required to achieve and sustain insulin independence following simultaneous islet-kidney transplantation.
Furthermore, we anticipate an improvement in creatinine clearance and a reduction in Interstitial Fibrosis/Tubular Atrophy in the transplanted renal allograft, and a reduction of "de novo" human anti-HLA antibody and auto-antibody formation against the respective donors.
Without calcineurin inhibitors or steroids, we hypothesize that belatacept, in conjunction with sirolimus and mycophenolic acid will provide balanced immunosuppression for combined islet-kidney transplantation.
Study Design
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Islets of Langerhans Transplantation
Intervention
Belatacept
Location
University of Wisconsin
Madison
Wisconsin
United States
53792
Status
Withdrawn
Source
University of Wisconsin, Madison
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT01033500
- Information obtained from ClinicalTrials.gov on May 22, 2013
Medical and Biotech [MESH] Definitions
Islets Of Langerhans Transplantation
The transference of pancreatic islets within an individual, between individuals of the same species, or between individuals of different species.
Nesidioblastosis
An inherited autosomal recessive syndrome characterized by the disorganized formation of new islets in the PANCREAS and PERSISTENT HYPERINSULINEMIA HYPOGLYCEMIA OF INFANCY. It is due to focal hyperplasia of pancreatic ISLET CELLS budding off from the ductal structures and forming new islets of Langerhans. Mutations in the islet cells involve the potassium channel gene KCNJ11 or the ATP-binding cassette transporter gene ABCC8, both on CHROMOSOME 11.
Langerhans Cell Sarcoma
Rare malignant neoplasm of dendritic LANGERHANS CELLS exhibiting atypical cytology, frequent mitoses, and aggressive clinical behavior. They can be distinguished from other histiocytic and dendritic proliferations by immunohistochemical and ultrastructure studies. Cytologically benign proliferations of Langerhans cells are called LANGERHANS CELL HISTIOCYTOSIS.
Histiocytosis, Langerhans-cell
A group of disorders resulting from the abnormal proliferation of and tissue infiltration by LANGERHANS CELLS which can be detected by their characteristic Birbeck granules (X bodies), or by monoclonal antibody staining for their surface CD1 ANTIGENS. Langerhans-cell granulomatosis can involve a single organ, or can be a systemic disorder.
Pancreas, Artificial
Devices for simulating the activity of the pancreas. They can be either electromechanical, consisting of a glucose sensor, computer, and insulin pump or bioartificial, consisting of isolated islets of Langerhans in an artificial membrane.
Clinical Trials
Imaging of Islet Transplantation With PET and MRT
Islets of Langerhans intended for clinical transplantation are labelled with a radioactive tracer. The tracer is retained in viable cells of the transplant. At infusion (transplantation) o...
Belatacept Pharmacokinetic Trial in Renal Transplantation
The purpose of this study is to assess the pharmacokinetics and safety of belatacept in de novo renal transplant subjects treated with belatacept-based immunosuppressant medication
Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression (BENEFIT)
The purpose of this study is to learn if Belatacept can provide protection from organ rejection following kidney transplantation while avoiding some of the toxic effects of standard immuno...
Pancreatic islets are the part of the pancreas that produce insulin and help control the blood sugar. This study aims to improve islet transplantation as a treatment for Type 1 Diabetes by...
The primary purpose of this study is to demonstrate the safety of allogeneic islet transplantation in type 1 diabetic patients performed at the University of Illinois at Chicago (UIC). The...
PubMed Articles
Cryopreservation of rat islets of Langerhans by vitrification.
Cryopreservation could be a possible means of addressing the shortage of islets of Langerhans. We investigated the effects of EDT324 solution on the vitrification of isolated rat islets of Langerhans....
Five-Year Safety and Efficacy of Belatacept in Renal Transplantation.
Belatacept is a first-in-class co-stimulation blocker in development for primary maintenance immunosuppression. A Phase II study comparing belatacept with cyclosporine (CsA) for prevention of acute re...
Belatacept : a new biological agent for maintenance immunosuppression in kidney transplantation.
Introduction: Over the past decades, calcineurin inhibitors (CNIs) have become the cornerstone of transplant immunosuppression. CNIs can exert negative effects on chronic allograft function along with...
Introduction. The effect of beta3-adrenergic receptor agonists on beta cells in the islets of Langerhans is not yet clear. This study examined the beta3-adrenergic receptor agonist on beta cells in th...
The islets of Langerhans, micro-organs for maintaining glucose homeostasis, range in size from small clusters of
