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

• Sponsor: Imperial College London (Other)
• Overall Status: Completed
• CT.gov ID: NCT00788827
• Collaborator: (none)
• Enrollment: 7
• Location: 1
• Arm: 1
• Actual Duration (Months): 53.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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

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 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Autologous stem cellsAutologous stem cells
• 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
• Actual Study Start Date: Nov 1, 2008
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Experienced Adverse Events [14 days]

   Safety will be evaluated in terms of adverse events graded according to CTCTAE toxicity criteria and laboratory test results. All adverse events will also be graded for relationship to treatment and as expected and unexpected.

Secondary Outcome Measures

1. Hba1C Data of Pre and Post Stem Cell Infusion [12 weeks]

   Mean HbA1c laboratory measurements pre and post stem cell infusion

2. Insulin Level [12 weeks]

   Mean insulin requirement was calculated for each participant pre and post stem cell infusion

3. Amylase Level [12 weeks]

   Each participant had mean amylase data analysed to give a pre and post mean result

4. Serum Creatinine [12 weeks]

   Each participant had serum creatinine analysis pre and post stem cell infusion to give mean result

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Imperial College NHS Healthcare Trust, Hammersmith Hospital	London		United Kingdom	W12 0HS

Sponsors and Collaborators

• Imperial College London

Investigators

• Principal Investigator: Charles Pusey, MD, Imperial College London

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Imperial College London
• ClinicalTrials.gov Identifier: NCT00788827
• Other Study ID Numbers: HHSC 005; CRO0472
• First Posted: Nov 11, 2008
• Last Update Posted: Nov 18, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Imperial College London: diabetes type I; diabetes type 2; renal transplant; stem cells; successful renal transplant
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1

Study Results

Participant Flow

Arm/Group Title	Autologous CD34+ Stem Cells
Arm/Group Description	Up to 5 x 10 log 8 of autologous stem cells on a single occasion Autologous CD34+ stem cells: Up to 5 x 10 log 8 of autologous stem cells on a single occasion
Period Title: Overall Study
STARTED	7
COMPLETED	5
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Single Arm
Arm/Group Description	Autologous CD34+ Stem Cells
Overall Participants	7
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	7 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.6 (4.2)
Sex: Female, Male (Count of Participants)
Female	2 28.6%
Male	5 71.4%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
United Kingdom	7 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Experienced Adverse Events
Description	Safety will be evaluated in terms of adverse events graded according to CTCTAE 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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Autologous Stem Cells
Arm/Group Description	Up to 5 x 10 log 8 of autologous stem cells on a single occasion Autologous CD34+ stem cells: Up to 5 x 10 log 8 of autologous stem cells on a single occasion
Measure Participants	7
Haematoma at femoral catheter insertion	1 14.3%
Fatigue	7 100%

2. Secondary Outcome

Title	Hba1C Data of Pre and Post Stem Cell Infusion
Description	Mean HbA1c laboratory measurements pre and post stem cell infusion
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Patients who were infused with stem cells

Arm/Group Title	Pre Infusion of Stem Cells	Post Infusion of Stem Cells
Arm/Group Description	Before the infusion of stem cells	After the infusion of stem cells
Measure Participants	5	5
Mean (Standard Deviation) [percentage]	7.2 (1.3)	7.24 (1.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Autologous Stem Cells, Post Infusion of Stem Cells
	Comments	Each participants Hba1c (%) lab result was analysed pre and post stem cell infusion to achieve 2 mean readings per participant.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Mixed Models Analysis
	Comments

3. Secondary Outcome

Title	Insulin Level
Description	Mean insulin requirement was calculated for each participant pre and post stem cell infusion
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Participants who received a stem cell infusion

Arm/Group Title	Pre Infusion of Stem Cells	Post Infusion of Stem Cells
Arm/Group Description	Before the infusion of stem cells	After the infusion of stem cells
Measure Participants	5	5
Mean (Standard Deviation) [iu/day]	59.4 (25.7)	54.06 (18.2)

4. Secondary Outcome

Title	Amylase Level
Description	Each participant had mean amylase data analysed to give a pre and post mean result
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Participants who received a stem cell infusion

Arm/Group Title	Pre Infusion of Stem Cells	Post Infusion of Stem Cells
Arm/Group Description	Before the infusion of stem cells	After the infusion of stem cells
Measure Participants	5	5
Mean (Standard Deviation) [units/L]	48.49 (25.2)	75.52 (34.2)

5. Secondary Outcome

Title	Serum Creatinine
Description	Each participant had serum creatinine analysis pre and post stem cell infusion to give mean result
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Participants who received stem cell infusion

Arm/Group Title	Pre Infusion of Stem Cells	Post Infusion of Stem Cells
Arm/Group Description	Before the infusion of stem cells	After the infusion of stem cells
Measure Participants	5	5
Mean (Standard Deviation) [umol/L]	128.22 (11.9)	118.64 (15.5)

Adverse Events

Time Frame	12 weeks
Arm/Group Title	Single Arm
Arm/Group Description	Autologous stem cells
All Cause Mortality
	Single Arm
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Serious Adverse Events
	Single Arm
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Other (Not Including Serious) Adverse Events
	Single Arm
	Affected / at Risk (%)	# Events
Total	7/7 (100%)
Blood and lymphatic system disorders
Haemotoma	1/7 (14.3%)	1
Nervous system disorders
Fatigue	7/7 (100%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.