Objective
The primary objective of this proof of concept study is to determine the ability of the intracutaneous (under the skin) site, created following integration of the special foam under the skin, to support islet survival and function in a type 1 diabetic population, as measured by human c-peptide assay. Secondary objectives include measuring the impact of the transplanted islets on blood sugar control using measures including insulin usage, blood sugar control and HbA1c at 3 and 6 months. Quality of life scores will also be collected before and after transplant to measure the success of the procedure from the patients perspective.
Background Rationale
The specialized foam material which forms the basis of this application, has been clinically developed for the management of severe burns and major trauma over the preceding 14 years, and creates a unique intracutaneous (under the skin) space, unlike any other commercially available skin product . The foam has undergone extensive clinical trials in burns and has US Food and Drug Administration and Australian Therapeutics Goods Administration regulation and licensing. The foam is extremely safe and has been used in vulnerable (major burn victims or people with suppressed immune systems) patient populations without adverse effects. Importantly for this application the foam creates a long lasting, dense blood vessel circulation that can be seen by real-time imaging in patients who have previously received a foam transplant under the skin. In the laboratory we have shown that the foam can support islet transplantation under the skin using several different models of diabetes. These experiments show that new blood vessel formation within the intracutaneous (under the skin) space using the foam creates an environment in which islets can survive and function long term. This has resulted in the cure of diabetes in several different models and islets have survived out to more than 400 days at which time the experiment was ended.
Based on these studies we hypothesise that: A intracutaneous (under the skin) transplant site created by implantation of the foam will create a new blood vessel circulation environment that supports the survival and function of human islets in type-1 diabetic individuals.
Description of Project
A proof of concept (POC) clinical trial of intracutaneous (under the skin) islet transplantation in type 1 diabetics with a functioning kidney transplant will be performed. In this POC trial a total of 5 patients will receive a special foam transplant under the skin that promotes the growth of new blood vessels. Then approximately 16-46 days later islets will be transplanted under the skin into the newly created blood vessels. These new blood vessels will support the islets helping them to survive the transplant procedure and then long-term allow the islets to control the patients diabetes. With a sufficient number of islet cells transplanted the patient will no longer require insulin injections to control their blood sugar levels. If successful this procedure will replace the current islet transplant process which requires the islets be transplanted into the patients liver. There are many reasons why the liver is not the best place for the islets and therefore any new transplant procedure that negates this step will have a profound impact on the future management of this disease.
Anticipated Outcome
This “proof of concept” study will determine if islets transplanted under the skin have a positive impact on type 1 diabetes control. This first in human study will answer the question concerning the ability of the foam to create an environment that allows survival and function of islet cells. The group of subjects in this trial will gain access to a diabetes therapy that they would otherwise be excluded from receiving, with the potential benefits of improved blood sugar control, possibly no longer requiring insulin injections to control their disease and therefore a reduction in their risk of developing future diabetic complications as a result of poorly controlled disease. None of these benefits are achievable with current diabetic therapy (insulin injections, insulin pumps). If this trial is successful it will provide the necessary data to expand this technology to other patient populations with type 1 diabetes.
Relevance to T1D
The knowledge gained from this trial has the potential to change the way in which islet transplantation is performed into the future. With significant improvement in diabetes management outcomes, reduction in anti rejection drug medication, greater use of donor organs, real-time monitoring of the transplanted islets within the patient, improved access for more type 1 diabetics and significant reductions in health care costs all potential outcomes. It will also be the basis for performing a multi-centre trial of the procedure to compare outcomes with the current islet transplant procedure, where islets are placed into the liver. Furthermore, the significant knowledge gained from this trial has the potential to benefit a large number of type 1 diabetics in the future through greater access to this treatment modality.