None listed
Conditions
Brief summary
Clinical Islet Transplantation at our center, akin to others internationally, achieves insulin independence rates of ~80% at 1 year in hypoglycemic unaware type 1 diabetics with poorly controlled disease. A major problem with current islet cell transplantation is the delivery of the islets into the portal circulation (via infusion into the liver). Up to 75% of the transplanted islet mass is lost within the first 24 hours due to low oxygen levels in the portal circulation and the instant blood mediated inflammatory reaction (IBMIR). Thus one of the major aims for the field of islet transplantation has been to develop a vascularised alternative site for islet transplantation that avoids the portal circulation. The aim of this application is to change the current paradigm of beta cell replacement with intra-portal islet transplantation, by establishing a clinical protocol to place adult islets in a pre-vascularized “intracutaneous” space. The intracutaneous space represents an attractive site for islet transplantation (ease of access, administration, monitoring, removal or replacement), however, it has been attempted unsuccessfully by groups in the past. The reason for failure of the ‘normal’ intracutaneous site is that the collagen structure produces a low oxygen (hypoxic) environment incapable of supporting islet survival and function. The BTM integrated into the intracutaneous site is much different! Implanting BTM into the intracutaneous site prior to islet transplant enables the formation of a dense vascular bed which is essential for islet survival and function. It is hypothesised that the proposed pilot study will demonstrate that the techniques described result in the successful intracutaneous seeding of human islets capable of secreting insulin to control blood glucose levels.
Interventions
This study is prospective, non-controlled, pilot proof-of-concept study of safety and design property achievement. It is a combination of two clinically approved products; cadaveric islets - transplanted into the liver for treatment of hypoglycemic unaware type 1 diabetics with poorly controlled disease and the Biodegradable Temporizing Matrix (BTM) - a synthetic polymer approved for the treatment of full thickness burns.
In combination, the BTM is implanted into a surgically created wound (appr
This study is prospective, non-controlled, pilot proof-of-concept study of safety and design property achievement. It is a combination of two clinically approved products; cadaveric islets - transplanted into the liver for treatment of hypoglycemic unaware type 1 diabetics with poorly controlled disease and the Biodegradable Temporizing Matrix (BTM) - a synthetic polymer approved for the treatment of full thickness burns. In combination, the BTM is implanted into a surgically created wound (approximately 10X4cm elliptical wound) in the inter-biceps/triceps groove of the medial arm in the trial participant. Then following a period of integration (>17 days) cadaveric islets from a consented organ donor are transplanted into the newly created hypervascular site (an alternative to the intrahepatic site). The wound creation and BTM implant will be performed by a burns sugeon (Royal Adelaide Hospital) who has many years experience performing similar surguries to treat full thickness burns using the BTM. It is anticipated this process will take less than a hour to complete. The islet transplant process will take less than 1 hour to complete and will be performed by the Islet transplant scientist, who has over 10 years experience performing islet transplants within the Nationally Funded Centres - Islet transplant program at the Royal Adelaide Hospital. Wound site and BTM integration will be monitored at dressing changes and photographed to document progress.
Sponsors
Royal Adelaide Hospital
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
50 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Patients with Type 1 Diabetes Mellitus who are recipients of a functional renal allograft (glomerular filtration rate of >40 ml/min) and taking immunosuppressant medication following that allograft.
Exclusion criteria
Pregnancy/Lactation Active infection or malignancy (other than locally controlled squamous cell carcinoma or basal cell carcinoma) Non-English speakers (from an informed consent perspective), unless an information and consent form in the subject’s language is available along with a study coordinator capable of answering questions in that language. Known allergy/previous reaction to polyurethane dressing materials Unwillingness to consent
Outcome results
None listed