Type 1 DiabetesPhase 2NCT01341899
Efficacy and Safety Study of Autologous Hematopoietic Stem Cell Transplantation to Treat New Onset Type 1 Diabetes
A Phase 2 study testing immunosuppression and stem cell transplantation in people with Type 1 Diabetes, run by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School at 1 site in China.
Trial summary
Type 1 diabetes is an autoimmune disease and results from T cell autoimmunity mediated destruction of the majority of insulin-producing pancreatic β-cells. Hence,the development of new therapies to control T cell autoimmunity, and to preserve the remaining β-cell function will be of great significance in managing… Read more about this study
- Who is it for?
- Ages 8 to 35 years
- Conditions the study is for
- Type 1 Diabetes
- What is being tested?
- immunosuppression and stem cell transplantation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteChina
- Study dates
- Jun 2006to Dec 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- diagnosis of diabetes according to the guidelines of the World Health Organization 1999
- the duration of diabetes is no more than 12 months
- positive for for glutamic acid decarboxylase antibody (GADA), protein tyrosine phosphatase antibody (IA-2A), islet cell antibody (ICA) and/or insulin autoantibody (IAAs)
Who cannot join
- pregnancy
- mental disorders
- blood diseases
- the presence of any other severe diseases that could potentially influence the transplantation outcomes
Trial locations and contacts
1 site in 1 country.
China1 site
at Division of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University
Nanjing, Jiangsu, 210008
About this study
Official title: Prospective Study of Autologous Hematopoietic Stem Cell Transplantation to Treat New Onset Type 1 Diabetes
Type 1 diabetes is an autoimmune disease and results from T cell autoimmunity mediated destruction of the majority of insulin-producing pancreatic β-cells. Hence,the development of new therapies to control T cell autoimmunity, and to preserve the remaining β-cell function will be of great significance in managing patients with type 1 diabetes
Autologous nonmyeloablative hematopoietic stem cell transplantation (AHST) has been tested for the treatment of patients with new onset of type 1 diabetes. This therapeutic strategy can result in exogenous insulin independence by destroying pathogenic memory T cells and preserving the remaining β-cell function.
Read more
However, little is known about the efficacy of AHST in the dynamics of immunocompetent cell reconstitution and how the reconstituted immune system regulates β-cell specific antibody response. Furthermore, many Chinese patients at diagnosis of type 1 diabetes have progressed to develop diabetic ketoacidosis (DKA). Whether treatment with AHST could still achieve adequate glycemic control and preserve the β-cell function and what the factors are associated with the therapeutic efficacy have not been explored.
This is a phase Ⅱ clinical trial in patients who have been diagnosed with type 1 diabetes within the previous 12 months.This study is to determine:
- The effects of autologous hematopoietic stem cell transplantation on the reconstitution of immune system
- β-cell preservation following stem cell transplantation
- The potential factors affecting efficacy of stem cell transplantation
- Whether this new therapy is safe.
Read the detailed description
Patients diagnosed with type 1 diabetes within the previous 12 months will be recruited into this study.Hematopoietic stem cells were mobilized with cyclophosphamide (CY, 2.0g/m2) and granulocyte colony stimulating factor (10 μg/kg per day) and then collected from peripheral blood by leukapheresis and cryopreserved. The cells were infused after conditioning with CY (200 mg/kg) and rabbit antithymocyte globulin (4.5 mg/kg). All the included patients undergoing AHST complied with blood glucose self-monitoring and scheduled medical appointments.Their blood samples were obtained for measuring the frequency of lymphocytes and the levels of plasma hemoglobin A1c (HbA1c), serum C-peptide, islet antibodies, and cytokines longitudinally.
Ages Eligible for Study: no more than 35 years
Genders Eligible for Study: both
Islet Autoantibodies Eligible for Study: positive for glutamic acid decarboxylase antibody (GADA), protein tyrosine phosphatase antibody (IA-2A), islet cell antibody (ICA) and/or insulin autoantibody (IAAs)
- Conditions
- Type 1 Diabetes
- Being tested
- immunosuppression and stem cell transplantation
- Keywords
- Type 1 diabetes, stem cell, C-peptide, Immune function
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
immunosuppression and stem cell transplantationProcedure or surgery
Also called nonmyeloablative stem cell transplantation
Hematopoietic stem cells were mobilized with cyclophosphamide (CY, 2.0 g/m2) and granulocyte colonystimulating factor (10 μg/kg per day) and then collected from peripheral blood by leukapheresis and cryopreserved. The cells were infused after conditioning with CY (200 mg/kg) and rabbit antithymocyte globulin (4.5 mg/kg).
| Study group | Role | What they receive |
|---|---|---|
| stem cell transplantation | Experimental | Not described Receives: Procedure: immunosuppression and stem cell transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in C-peptide levels during standard-meal tolerance test from baseline to different time points after transplantation
Measured: 3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years
Secondary outcomes (5)
Changes in serum levels of HbA1c from baseline to different time points after transplantation
Measured: 3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years
Temporal changes of exogenous insulin requirement from baseline to different time points after transplantation
Measured: 3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years
Dynamic changes in islet antibody status from baseline to different time points after transplantation
Measured: 3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years
Dynamic changes in lymphocyte immunophenotyping and cytokine profiles from baseline to different time points after transplantation
Measured: 3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years
mortality and dysfunction of other endocrine glands
Measured: up to 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2011 (estimated)
- Study startJun 2006
- Primary completionDec 2012
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- More trials run by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dalong Zhu, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
- Investigators
- Dalong Zhu, MD,PhD, Principal investigator, the Affiliated Drum Tower Hospital of Nanjing University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01341899
- Sponsor's protocol ID
- ZKX07012
- Status last verified
- Oct 2016
- First submitted
- 21 Apr 2011
- Last updated
- 1 Nov 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Li L, Shen S, Ouyang J, Hu Y, Hu L, Cui W, Zhang N, Zhuge YZ, Chen B, Xu J, Zhu D. Autologous hematopoietic stem cell transplantation modulates immunocompetent cells and improves beta-cell function in Chinese patients with new onset of type 1 diabetes. J Clin Endocrinol Metab. 2012 May;97(5):1729-36. doi: 10.1210/jc.2011-2188. Epub 2012 Mar 14.
PubMed 22419704
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Study of Autologous Hematopoietic Stem Cell Transplantation to Treat New Onset Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT01341899
- Acronym / sponsor ID
- ZKX07012
- Conditions
- Type 1 Diabetes
- Keywords
- Type 1 diabetes, stem cell, C-peptide, Immune function
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolUniversity, hospital or other
- Study start
- Jun 2006
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 26 Apr 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Type 1 diabetes is an autoimmune disease and results from T cell autoimmunity mediated destruction of the majority of insulin-producing pancreatic β-cells. Hence,the development of new therapies to control T cell autoimmunity, and to preserve the remaining β-cell function will be of great significance in managing patients with type 1 diabetes
Autologous nonmyeloablative hematopoietic stem cell transplantation (AHST) has been tested for the treatment of patients with new onset of type 1 diabetes. This therapeutic strategy can result in exogenous insulin independence by destroying pathogenic memory T cells and preserving the remaining β-cell function.
However, little is known about the efficacy of AHST in the dynamics of immunocompetent cell reconstitution and how the reconstituted immune system regulates β-cell specific antibody response. Furthermore, many Chinese patients at diagnosis of type 1 diabetes have progressed to develop diabetic ketoacidosis (DKA). Whether treatment with AHST could still achieve adequate glycemic control and preserve the β-cell function and what the factors are associated with the therapeutic efficacy have not been explored.
This is a phase Ⅱ clinical trial in patients who have been diagnosed with type 1 diabetes within the previous 12 months.This study is to determine:
- The effects of autologous hematopoietic stem cell transplantation on the reconstitution of immune system
- β-cell preservation following stem cell transplantation
- The potential factors affecting efficacy of stem cell transplantation
- Whether this new therapy is safe.
Detailed description
Patients diagnosed with type 1 diabetes within the previous 12 months will be recruited into this study.Hematopoietic stem cells were mobilized with cyclophosphamide (CY, 2.0g/m2) and granulocyte colony stimulating factor (10 μg/kg per day) and then collected from peripheral blood by leukapheresis and cryopreserved. The cells were infused after conditioning with CY (200 mg/kg) and rabbit antithymocyte globulin (4.5 mg/kg). All the included patients undergoing AHST complied with blood glucose self-monitoring and scheduled medical appointments.Their blood samples were obtained for measuring the frequency of lymphocytes and the levels of plasma hemoglobin A1c (HbA1c), serum C-peptide, islet antibodies, and cytokines longitudinally.
Ages Eligible for Study: no more than 35 years
Genders Eligible for Study: both
Islet Autoantibodies Eligible for Study: positive for glutamic acid decarboxylase antibody (GADA), protein tyrosine phosphatase antibody (IA-2A), islet cell antibody (ICA) and/or insulin autoantibody (IAAs)
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| stem cell transplantation | Experimental | Procedure: immunosuppression and stem cell transplantation |
Who may qualify
- Ages
- 8 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- diagnosis of diabetes according to the guidelines of the World Health Organization 1999
- the duration of diabetes is no more than 12 months
- positive for for glutamic acid decarboxylase antibody (GADA), protein tyrosine phosphatase antibody (IA-2A), islet cell antibody (ICA) and/or insulin autoantibody (IAAs)
Key exclusion criteria (4 listed)
- pregnancy
- mental disorders
- blood diseases
- the presence of any other severe diseases that could potentially influence the transplantation outcomes
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| immunosuppression and stem cell transplantationAlso: nonmyeloablative stem cell transplantationHematopoietic stem cells were mobilized with cyclophosphamide (CY, 2.0 g/m2) and granulocyte colonystimulating factor (10 μg/kg per day) and then collected from peripheral blood by leukapheresis and cryopreserved. The cells were infused after conditioning with CY (200 mg/kg) and rabbit antithymocyte globulin (4.5 mg/kg). | Procedure or surgery | stem cell transplantation |
Primary outcome
Changes in C-peptide levels during standard-meal tolerance test from baseline to different time points after transplantation
Time frame: 3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years
5 secondary outcomes
Changes in serum levels of HbA1c from baseline to different time points after transplantation
Time frame: 3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years
Temporal changes of exogenous insulin requirement from baseline to different time points after transplantation
Time frame: 3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years
Dynamic changes in islet antibody status from baseline to different time points after transplantation
Time frame: 3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years
Dynamic changes in lymphocyte immunophenotyping and cytokine profiles from baseline to different time points after transplantation
Time frame: 3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years
mortality and dysfunction of other endocrine glands
Time frame: up to 10 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2016.
- Derived from this study: PubMed 22419704Li L, Shen S, Ouyang J, Hu Y, Hu L, Cui W, Zhang N, Zhuge YZ, Chen B, Xu J, Zhu D. Autologous hematopoietic stem cell transplantation modulates immunocompetent cells and improves beta-cell function in Chinese patients with new onset of type 1 diabetes. J Clin Endocrinol Metab. 2012 May;97(5):1729-36. doi: 10.1210/jc.2011-2188. Epub 2012 Mar 14.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dalong Zhu, MD,PhD principal investigator
the Affiliated Drum Tower Hospital of Nanjing University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing immunosuppression and stem cell transplantation in people with Type 1 Diabetes, run by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in C-peptide levels during standard-meal tolerance test from baseline to different time points after transplantation (time frame: 3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01341899, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2016.