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Autologous Adult Stem Cells to Patients With Type 1 Diabetes and a Successful Renal Transplant

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ClinicalTrials.gov Identifier: NCT00788827
Recruitment Status : Completed
First Posted : November 11, 2008
Last Update Posted : January 22, 2015
Sponsor:
Information provided by (Responsible Party):
Imperial College London

Tracking Information
First Submitted Date  ICMJE November 10, 2008
First Posted Date  ICMJE November 11, 2008
Last Update Posted Date January 22, 2015
Study Start Date  ICMJE November 2008
Actual Primary Completion Date May 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 10, 2008)
Safety will be evaluated in terms of adverse events graded according to CTC toxicity criteria and laboratory test results. All adverse events will also be graded for relationship to treatment and as expected and unexpected. [ Time Frame: 14 days ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00788827 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 10, 2008)
To assess improvement in endocrine pancreatic function as measured by serological and biochemical analysis and determine any symptomatic improvements as they are reported by the patients. [ Time Frame: 12 weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Autologous Adult Stem Cells to Patients With Type 1 Diabetes and a Successful Renal Transplant
Official Title  ICMJE 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
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 (CD34 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. 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Type 1 Diabetes
  • Type 2 Diabetes
Intervention  ICMJE Biological: Autologous CD34+ stem cells
Up to 5 x 10 log 8 of autologous stem cells on a single occasion
Study Arms  ICMJE Experimental: Autologous CD34+ stem cells
Up to 5 x 10 log 8 of autologous stem cells on a single occasion
Intervention: Biological: Autologous CD34+ stem cells
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 21, 2015)
7
Original Estimated Enrollment  ICMJE
 (submitted: November 10, 2008)
18
Actual Study Completion Date  ICMJE May 2013
Actual Primary Completion Date May 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female patients aged from 16 to 65 years of age
  • Patient with Type I or Type 2 diabetes mellitus plus:
  • Successful previous kidney transplant.
  • Good kidney allograft function /no episodes of rejection for at least one year post-transplant
  • Not taking steroids as part of standard immuno-suppression
  • Has a WHO performance score of less than 2
  • Has a life expectancy of at least 3 months
  • Ability to give written consent
  • Women of childbearing potential may be included, but must use a reliable and appropriate contraceptive method

Exclusion Criteria:

  • Patients below the age of 16 or above the age of 65 years
  • Patients with chronic pancreatitis and poor exocrine pancreatic function
  • Pregnant or lactating women
  • Patients with recent recurrent GI bleeding or spontaneous bacterial peritonitis
  • Patients with evidence of HIV or other life threatening infection
  • Patients unable to give written consent
  • Patients with a history of hypersensitivity to G-CSF
  • Patients who have been included in any other clinical trial within the previous month
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years to 65 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00788827
Other Study ID Numbers  ICMJE HHSC 005
CRO0472 ( Other Identifier: Imperial College London )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Imperial College London
Study Sponsor  ICMJE Imperial College London
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Charles Pusey, MD Imperial College London
PRS Account Imperial College London
Verification Date July 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP