Ignite Creation Date:
2024-05-05 @ 8:02 PM
Last Modification Date:
2024-10-26 @ 9:57 AM
Study NCT ID:
NCT00788827
Status:
COMPLETED
Last Update Posted:
2019-11-18
First Post:
2008-11-10
Brief Title:
Autologous Adult Stem Cells to Patients With Type 1 Diabetes and a Successful Renal Transplant
Sponsor:
Imperial College London
Organization:
Imperial College London
Study Overview
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
Status:
COMPLETED
Status Verified Date:
2019-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
Detailed Description:
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 reagentsgrowth 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
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 reagentsgrowth 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| CRO0472 | OTHER | Imperial College London | None |