Type 2 Diabetes Clinical Trial
Official title:
A Phase I Safety and Tolerability Study Following the Infusion of Autologous Expanded Progeny of an Adult CD34+ Stem Cell Subset (InsulinCytes) to Patients With Type I Diabetes Mellitus and a Successful Renal Transplant
This is a phase I study to assess the safety and tolerability of infusing expanded stem cells into the pancreas of patients with type I diabetes and a successful renal transplant. The stem cells used in this study occur naturally in the body and are collected from each recipient by a procedure called leukapheresis. The cells are then expanded and differentiated into insulin-like cells in a sterile suite before being injected into the body or tail of the pancreas of the recipient.
Islet transplantation as a potential treatment for diabetes has been investigated extensively
over the past 10 years. Such an approach, however, will always be limited mainly because it
is difficult to obtain sufficiently large numbers of purified islets from cadaveric donors.
One alternative to organ or tissue transplantation is to use a renewable source of cells.
Adult stem cells are clonogenic cells capable of both self-renewal and multilineage
differentiation. These cells have the potential to proliferate and differentiate into any
type of cell and to be genetically modified in vitro, thus providing cells, which can be
isolated and used for transplantation.
Recent studies have given well-defined differentiation protocols, which can be used to guide
stem cells into specific cell lineages as neurons, cardiomyocytes and insulin-secreting
cells. Moreover, these derived cells have been useful in different animal models. In this
regard, insulin-secreting cells derived from R1 mouse embryonic stem cells restore blood
glucose concentrations to normal when they are transplanted into streptozotocin-induced
diabetic animals. Our group has isolated stem cells (Cluster Designated (CD) 34 positive
subset of stem cells) that are capable of differentiating into multiple tissue types ex vivo.
In defined conditions, in culture, about 40 percent of the cells produce insulin and reduce
blood sugar levels in streptozotocin-induced mice.
Clinically, we have performed a phase I trial of stem cell administration to patients with
liver insufficiency. The procedure was well tolerated with no specific side effects and with
sustained signs of clinical benefit. These results support this protocol for the application
of adult stem cell therapy in the treatment of diabetes.
In order to evaluate potential clinical applications for these recent advances we have
designed a prospective Phase I clinical study of the expanded progeny of an adult CD34
positive subset (InsulinCytes) injected directly into the body and tail of the pancreas of
the participants via selective catheterisation of the splenic artery. The study group
consists of patients with complicated diabetes mellitus type I plus kidney transplantation
with the aim of ascertaining whether this confers clinical benefit as a treatment model for
diabetes.
Granulocyte colony-stimulating factor (G-CSF) will be administered to suitable patients to
mobilise their haematopoietic stem cells (HSCs) from the bone marrow into the peripheral
circulation. These blood cells will be collected from each patient by leukapheresis. CD34
positive stem cells will then be isolated by immunoselection and introduced into a Nunc cell
factory where the subset of CD34 positive stem cells will be allowed to attach to the plastic
trays within the cell factory for 2 hours at 37 degrees C in 5 percent carbon dioxide. After
this period the non-attached CD34 positive cells will be washed from the system and the
progeny of the attached cells secreted into the supernatant media expanded in the presence of
growth medium supplemented with growth factors. At the end of 6 days expansion, the stem
cells will be differentiated into insulin and c-peptide protein excreting cells over the next
14 days by the addition of specified reagents/growth factors and continued incubation at 37
degrees C in 5 percent carbon dioxide in accordance with the principles of Good Manufacturing
Practice (GMP). As an optional step the cells can be labelled with iron oxide to allow
tracking of the cells by Magnetic Resonance Imaging (MRI) scan, before being infused into the
patient.
An ongoing institute experience with liver failure patients who have been infused with
undifferentiated stem cells has shown that an administered dose of up to 2 x 10 log 9 cells
was well tolerated. The proposed study group will consist of 10 Type I or Type 2 diabetic
patients who have had a successful previous kidney transplant.
The primary purpose of the study is to assess the safety and tolerance of stem cell infusion
into the pancreas and then to assess the impact of this new modality in the treatment of
diabetes.
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