Type 1 Diabetes MellitusPhase 2NCT00807651
Autologous Hematopoietic Stem Cell Transplantation for Early Onset Type 1 Diabetes
A Phase 2 study testing AHSCT and Insulin therapy in people with Type 1 Diabetes Mellitus, run by Shanghai Jiao Tong University School of Medicine at 1 site in China.
Trial summary
This is a phase II trial in individuals who have been diagnosed with type 1 diabetes within the previous 6 months. The study is evaluating whether stem cell transplantation is safe when chemotherapy and immunotherapy are used in combination and if it has immune resetting effect that may halt the immune attack to… Read more about this study
- Who is it for?
- Ages 14 to 35 years
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- AHSCT and Insulin therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteChina
- Study dates
- Feb 2008to Dec 2016
- 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 14 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Type 1 diabetes mellitus diagnosed by clinical/metabolic parameters and positive anti-GAD antibody
- Less than 6 months from diagnosis
Who cannot join
- Previous diabetic ketoacidosis
- Pregnancy
- Severe psychiatric disorder
- Severe organic impairment (renal, hepatic, cardiac, pulmonary)
- Active infectious disease
- Previous or present neoplastic disease
Trial locations and contacts
1 site in 1 country.
China1 site
Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, 200025
About this study
Official title: Safety and Efficacy Study of Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation for Early Onset Type 1 Diabetes-a Phase II Study
This is a phase II trial in individuals who have been diagnosed with type 1 diabetes within the previous 6 months. The study is evaluating whether stem cell transplantation is safe when chemotherapy and immunotherapy are used in combination and if it has immune resetting effect that may halt the immune attack to pancreas islets and thus preserve the body's own insulin production.
Read the detailed description
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks the insulin-producing beta cells in the pancreas. Generally, at the time someone is diagnosed with type 1 diabetes, not all of a person's beta cells have been destroyed. It's important to preserving the remaining precious beta cells so as to stop the diabetes progression.
The exact mechanism of action of Autologous Hematopoietic Stem Cell Transplantation(AHST) in autoimmune disorders is not fully understood. Preliminary data supported post-AHST immune resetting included an increase in thymus-derived naive T cells, decreased central-memory T cells, increased output of recent thymic emigrants, and recovery of a diverse but distinct T-cell receptor repertoire following AHST. In the patients of type 1 diabetes, decreasing titer of anti-GAD antibody may bring improvement of beta-cell function after intensive immunosuppression. Furthermore, there may exit the possibility of regeneration of beta cells from surviving beta cells or from pancreatic or bone marrow stem cells.
Patients recently diagnosed (less than 6 months) with type 1 diabetes mellitus proved by positive antibody against glutamic acid decarboxylase will be included in this study. Hematopoietic stem cells will be mobilized with cyclophosphamide (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 injected intravenously after conditioning with cyclophosphamide (200 mg/kg) and rabbit antithymocyte globulin (4.5 mg/kg). This procedure is performed in isolated rooms at the Bone Marrow Transplantation Unit of Shanghai Ruijin Hospital affiliated to Shanghai Jiao-Tong University School of Medicine. Patients will be discharged from the hospital 1 month after transplantation and continue the follow-ups for 3 years. Patients fitting the inclusion criteria but not agreeing to perform the transplantation are the control group and they will be followed in parallel with transplanted patients.
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- AHSCT, Insulin therapy
- Keywords
- Diabetes Mellitus, Stem cells, Autologous stem cell transplantation, Autoimmune diseases
- Medical subject headings
- Diabetes Mellitus, Type 1, Diabetes Mellitus, Autoimmune Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AHSCTProcedure or surgery
Also called hematopoietic stem cell
All study participants given written informed consent will perform autologous hematopoietic stem cell transplantation(AHSCT) and be treated with immunosuppression.
Insulin therapyDrug
Also called insulin injection therapy
All study participants not accepted written informed consent will received insulin therapy with consistent or multiply subcutaneous injection.
| Study group | Role | What they receive |
|---|---|---|
| insulin therapy | Active comparator | The participants not accepted written informed consent will receive insulin therapy Receives: Drug: Insulin therapy |
| AHSCT | Experimental | The participants accepted written informed consent will receive the therapy of autologous hematopoietic stem cell transplantation(AHSCT) Receives: Procedure: AHSCT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Exogenous insulin dose
Measured: 1 month, 3 months, 6 months, 12 months, 24 months, 36 months
Secondary outcomes (3)
Anti-GAD titres
Measured: 1 month, 3 months, 6 months, 12 months, 24 months, 36 months
C-peptide level
Measured: 1 month, 3 months, 6 months, 12 months, 24 months, 36 months
HbA1c level
Measured: 3 months, 6 months, 12 months, 24 months, 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2008 (estimated)
- Study startFeb 2008
- Primary completionJun 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Shanghai Jiao Tong University School of MedicineThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shanghai Jiao Tong University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Guang Ning, Shanghai Jiao Tong University School of Medicine
- Investigators
- Guang Ning, MD. PhD., Principal investigator, Shanghai Jiao Tong University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00807651
- Sponsor's protocol ID
- CCEMD006
- Status last verified
- Nov 2021
- First submitted
- 11 Dec 2008
- Last updated
- 18 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Voltarelli JC, Couri CE, Stracieri AB, Oliveira MC, Moraes DA, Pieroni F, Coutinho M, Malmegrim KC, Foss-Freitas MC, Simoes BP, Foss MC, Squiers E, Burt RK. Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA. 2007 Apr 11;297(14):1568-76. doi: 10.1001/jama.297.14.1568.
PubMed 17426276Ye L, Li L, Wan B, Yang M, Hong J, Gu W, Wang W, Ning G. Immune response after autologous hematopoietic stem cell transplantation in type 1 diabetes mellitus. Stem Cell Res Ther. 2017 Apr 18;8(1):90. doi: 10.1186/s13287-017-0542-1.
PubMed 28420440Gu W, Hu J, Wang W, Li L, Tang W, Sun S, Cui W, Ye L, Zhang Y, Hong J, Zhu D, Ning G. Diabetic ketoacidosis at diagnosis influences complete remission after treatment with hematopoietic stem cell transplantation in adolescents with type 1 diabetes. Diabetes Care. 2012 Jul;35(7):1413-9. doi: 10.2337/dc11-2161.
PubMed 22723579Zhang X, Ye L, Hu J, Tang W, Liu R, Yang M, Hong J, Wang W, Ning G, Gu W. Acute response of peripheral blood cell to autologous hematopoietic stem cell transplantation in type 1 diabetic patient. PLoS One. 2012;7(2):e31887. doi: 10.1371/journal.pone.0031887. Epub 2012 Feb 22.
PubMed 22384093
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy Study of Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation for Early Onset Type 1 Diabetes-a Phase II Study
- ClinicalTrials.gov ID
- NCT00807651
- Acronym / sponsor ID
- CCEMD006
- Conditions
- Type 1 Diabetes Mellitus
- Keywords
- Diabetes Mellitus, Stem cells, Autologous stem cell transplantation, Autoimmune diseases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Shanghai Jiao Tong University School of MedicineUniversity, hospital or other
- Study start
- Feb 2008 (actual)
- Primary completion
- Jun 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 12 Dec 2008 (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.
This is a phase II trial in individuals who have been diagnosed with type 1 diabetes within the previous 6 months. The study is evaluating whether stem cell transplantation is safe when chemotherapy and immunotherapy are used in combination and if it has immune resetting effect that may halt the immune attack to pancreas islets and thus preserve the body's own insulin production.
Detailed description
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks the insulin-producing beta cells in the pancreas. Generally, at the time someone is diagnosed with type 1 diabetes, not all of a person's beta cells have been destroyed. It's important to preserving the remaining precious beta cells so as to stop the diabetes progression.
The exact mechanism of action of Autologous Hematopoietic Stem Cell Transplantation(AHST) in autoimmune disorders is not fully understood. Preliminary data supported post-AHST immune resetting included an increase in thymus-derived naive T cells, decreased central-memory T cells, increased output of recent thymic emigrants, and recovery of a diverse but distinct T-cell receptor repertoire following AHST. In the patients of type 1 diabetes, decreasing titer of anti-GAD antibody may bring improvement of beta-cell function after intensive immunosuppression. Furthermore, there may exit the possibility of regeneration of beta cells from surviving beta cells or from pancreatic or bone marrow stem cells.
Patients recently diagnosed (less than 6 months) with type 1 diabetes mellitus proved by positive antibody against glutamic acid decarboxylase will be included in this study. Hematopoietic stem cells will be mobilized with cyclophosphamide (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 injected intravenously after conditioning with cyclophosphamide (200 mg/kg) and rabbit antithymocyte globulin (4.5 mg/kg). This procedure is performed in isolated rooms at the Bone Marrow Transplantation Unit of Shanghai Ruijin Hospital affiliated to Shanghai Jiao-Tong University School of Medicine. Patients will be discharged from the hospital 1 month after transplantation and continue the follow-ups for 3 years. Patients fitting the inclusion criteria but not agreeing to perform the transplantation are the control group and they will be followed in parallel with transplanted patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| insulin therapy | Active comparator | Drug: Insulin therapyThe participants not accepted written informed consent will receive insulin therapy |
| AHSCT | Experimental | Procedure: AHSCTThe participants accepted written informed consent will receive the therapy of autologous hematopoietic stem cell transplantation(AHSCT) |
Who may qualify
- Ages
- 14 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- Type 1 diabetes mellitus diagnosed by clinical/metabolic parameters and positive anti-GAD antibody
- Less than 6 months from diagnosis
Key exclusion criteria (6 listed)
- Previous diabetic ketoacidosis
- Pregnancy
- Severe psychiatric disorder
- Severe organic impairment (renal, hepatic, cardiac, pulmonary)
- Active infectious disease
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 |
|---|---|---|
| AHSCTAlso: hematopoietic stem cellAll study participants given written informed consent will perform autologous hematopoietic stem cell transplantation(AHSCT) and be treated with immunosuppression. | Procedure or surgery | AHSCT |
| Insulin therapyAlso: insulin injection therapyAll study participants not accepted written informed consent will received insulin therapy with consistent or multiply subcutaneous injection. | Drug | insulin therapy |
Primary outcome
Exogenous insulin dose
Time frame: 1 month, 3 months, 6 months, 12 months, 24 months, 36 months
3 secondary outcomes
Anti-GAD titres
Time frame: 1 month, 3 months, 6 months, 12 months, 24 months, 36 months
C-peptide level
Time frame: 1 month, 3 months, 6 months, 12 months, 24 months, 36 months
HbA1c level
Time frame: 3 months, 6 months, 12 months, 24 months, 36 months
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 18 Nov 2021.
- Background: PubMed 17426276Voltarelli JC, Couri CE, Stracieri AB, Oliveira MC, Moraes DA, Pieroni F, Coutinho M, Malmegrim KC, Foss-Freitas MC, Simoes BP, Foss MC, Squiers E, Burt RK. Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA. 2007 Apr 11;297(14):1568-76. doi: 10.1001/jama.297.14.1568.
- Derived from this study: PubMed 28420440Ye L, Li L, Wan B, Yang M, Hong J, Gu W, Wang W, Ning G. Immune response after autologous hematopoietic stem cell transplantation in type 1 diabetes mellitus. Stem Cell Res Ther. 2017 Apr 18;8(1):90. doi: 10.1186/s13287-017-0542-1.
- Derived from this study: PubMed 22723579Gu W, Hu J, Wang W, Li L, Tang W, Sun S, Cui W, Ye L, Zhang Y, Hong J, Zhu D, Ning G. Diabetic ketoacidosis at diagnosis influences complete remission after treatment with hematopoietic stem cell transplantation in adolescents with type 1 diabetes. Diabetes Care. 2012 Jul;35(7):1413-9. doi: 10.2337/dc11-2161.
- Derived from this study: PubMed 22384093Zhang X, Ye L, Hu J, Tang W, Liu R, Yang M, Hong J, Wang W, Ning G, Gu W. Acute response of peripheral blood cell to autologous hematopoietic stem cell transplantation in type 1 diabetic patient. PLoS One. 2012;7(2):e31887. doi: 10.1371/journal.pone.0031887. Epub 2012 Feb 22.
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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.
Guang Ning, MD. PhD. principal investigator
Shanghai Jiao Tong University School of Medicine
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 AHSCT and Insulin therapy in people with Type 1 Diabetes Mellitus, run by Shanghai Jiao Tong University School of Medicine 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 2 inclusion and 6 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 18 Nov 2021. 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?
Exogenous insulin dose (time frame: 1 month, 3 months, 6 months, 12 months, 24 months, 36 months). 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 NCT00807651, which also lists 4 linked publications.
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 18 Nov 2021.