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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

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.

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Type 2 Diabetes Biological: Autologous CD34+ stem cells Phase 1

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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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : November 2008
Actual Primary Completion Date : May 2013
Actual Study Completion Date : May 2013

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Autologous CD34+ stem cells
Up to 5 x 10 log 8 of autologous stem cells on a single occasion
Biological: Autologous CD34+ stem cells
Up to 5 x 10 log 8 of autologous stem cells on a single occasion




Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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 ]


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Ages Eligible for Study:   16 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00788827


Locations
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United Kingdom
Imperial College NHS Healthcare Trust, Hammersmith Hospital
London, United Kingdom, W12 0HS
Sponsors and Collaborators
Imperial College London
Investigators
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Principal Investigator: Charles Pusey, MD Imperial College London

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Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT00788827     History of Changes
Other Study ID Numbers: HHSC 005
CRO0472 ( Other Identifier: Imperial College London )
First Posted: November 11, 2008    Key Record Dates
Last Update Posted: January 22, 2015
Last Verified: July 2011
Keywords provided by Imperial College London:
diabetes type I
diabetes type 2
renal transplant
stem cells
successful renal transplant
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases