Type 1 Diabetes MellitusPhase 1/2NCT00315133
Safety and Efficacy Study of Autologous Stem Cell Transplantation for Early Onset Type I Diabetes Mellitus
A Phase 1/2 study testing Immunosuppression and autologous stem cell transplantation in people with Type 1 Diabetes Mellitus, run by University of Sao Paulo at 1 site in Brazil.
Trial summary
The study evaluates the effect of inactivation of the immune system with chemotherapy and immunotherapy and infusion of bone marrow stem cells in early onset type 1 diabetes mellitus. Read more about this study
- Who is it for?
- Ages 12 to 35 years
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- Immunosuppression and autologous stem cell transplantation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteBrazil
- Study dates
- Dec 2003to Dec 2014
- Phase
- Phase 1/2
- 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 12 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 antibodies
- Less than 12 weeks 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.
Brazil1 site
Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
Ribeirão Preto, Ribeirão Preto, 14048-900
About this study
Official title: Autologous Hematopoietic Stem Cell Transplantation for Early Onset Type 1 Diabetes Mellitus- a Phase I/II Study
The study evaluates the effect of inactivation of the immune system with chemotherapy and immunotherapy and infusion of bone marrow stem cells in early onset type 1 diabetes mellitus. We hypothesize that reprograming the immune system will stop immune aggression to the insulin producing cells allowing their regeneration and thus decreasing or eliminating the need of exogenous insulin.
Read the detailed description
Patients from 12 to 35 years old with type I diabetes mellitus proved by anti-pancreatic beta cell antibodies and recently diagnosed (less than 6 weeks) will be included in this study. Peripheral blood hematopoietic stem cells will be mobilized from bone marrow of the patient with cyclophosphamide plus G-CSF (granulocyte-colony stimulating factor), collected by leukapheresis and cryopreserved. After 2-3 weeks, high dose immunosuppression is given (cyclophosphamide 200 mg/kg plus rabbit antithymocyte globulin 4.5 mg/kg) and stem cells are thawed and injected intravenously. This procedure is performed in isolated rooms at the Bone Marrow Transplantation Unit of the School of Medicine of Ribeirão Preto, University of São Paulo, Brazil. Patients are discharged from the hospital after engraftment and closely followed up to 2 months after transplantation (with at least weekly outpatient visits) and continue the followup for 5 years after transplantation. Clinical, hematological, metabolical and immunological evaluations are performed to analyse the effect of the transplant in the disease and in the hematopoetic and immunologic systems of the body. 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
- Immunosuppression and autologous stem cell transplantation
- 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.
Immunosuppression and autologous stem cell transplantationProcedure or surgery
Immunosuppression and autologous stem cell transplantation: Mobilization of hematopoietic stem cells (HSC) with cyclophosphamide (2 g/m2) and granulocyte-colony stimulating factor (G-CSF, 10 ug/kg/d), followed by collection and cryopreservation of unselected HSC and conditioning with cyclophosphamide (200 mg/kg) plus rabbit anti-thymocyte globulin (ATG 4.5 mg/kg).
| Study group | Role | What they receive |
|---|---|---|
| Transplant arm | Experimental | This is a single arm study. The intervention is immunosuppression and autologous stem cell transplantation. Receives: Procedure: Immunosuppression and autologous stem cell transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
C-peptide levels
Stimulated C-peptide levels will be measured.
Measured: Every 6 months
Secondary outcomes (6)
Transplant-related toxicity
Measured: Every 6 months or when reported
Anti-GAD titres
Measured: Every 6 months
Exogenous insulin dose
Number of international insulin units per kilogram per day in use will be registered.
Measured: Every 6 months
Hemoglobin A1C
Hb A1C will be measured.
Measured: Every 6 months
Immunologic reconstitution parameters
Measured: Yearly
Quality of Life
SF-36 questionnaire
Measured: Every year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2006 (estimated)
- Study startDec 2003
- Primary completionDec 2010
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)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 University of Sao PauloThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo
- Sponsor type
- University, hospital or other
- Collaborators
- Northwestern University, Genzyme, a Sanofi Company
- Responsible party
- Principal investigator, Julio C. Voltarelli, University of Sao Paulo
- Investigators
- Julio C Voltarelli, MD PhD, Principal investigator, University Hospital, School of Medicine of Ribeirão Preto, BrazilMaria C Oliveira, MD PhD, Study chair, University Hospital, Ribeirão Preto Medical School, Brazil
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00315133
- Sponsor's protocol ID
- HCFMRPUSP
- Status last verified
- Jan 2017
- First submitted
- 13 Apr 2006
- Last updated
- 18 Jan 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided: IPD may be shared if the responsible investigators feel it may increase understanding, reliability and reproducibility of the present study.
Publications
Burt RK, Oyama Y, Traynor A, Kenyon NS. Hematopoietic stem cell therapy for type 1 diabetes: induction of tolerance and islet cell neogenesis. Autoimmun Rev. 2002 May;1(3):133-8. doi: 10.1016/s1568-9972(02)00033-2.
PubMed 12849006Voltarelli 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 17426276Couri CE, Oliveira MC, Stracieri AB, Moraes DA, Pieroni F, Barros GM, Madeira MI, Malmegrim KC, Foss-Freitas MC, Simoes BP, Martinez EZ, Foss MC, Burt RK, Voltarelli JC. C-peptide levels and insulin independence following autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA. 2009 Apr 15;301(15):1573-9. doi: 10.1001/jama.2009.470.
PubMed 19366777
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Autologous Hematopoietic Stem Cell Transplantation for Early Onset Type 1 Diabetes Mellitus- a Phase I/II Study
- ClinicalTrials.gov ID
- NCT00315133
- Acronym / sponsor ID
- HCFMRPUSP
- Conditions
- Type 1 Diabetes Mellitus
- Keywords
- Diabetes mellitus, Stem cells, Autologous stem cell transplantation, Autoimmune diseases
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- University of Sao PauloUniversity, hospital or other
- Collaborators
- Northwestern University, Genzyme, a Sanofi Company
- Study start
- Dec 2003
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 17 Apr 2006 (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.
The study evaluates the effect of inactivation of the immune system with chemotherapy and immunotherapy and infusion of bone marrow stem cells in early onset type 1 diabetes mellitus. We hypothesize that reprograming the immune system will stop immune aggression to the insulin producing cells allowing their regeneration and thus decreasing or eliminating the need of exogenous insulin.
Detailed description
Patients from 12 to 35 years old with type I diabetes mellitus proved by anti-pancreatic beta cell antibodies and recently diagnosed (less than 6 weeks) will be included in this study. Peripheral blood hematopoietic stem cells will be mobilized from bone marrow of the patient with cyclophosphamide plus G-CSF (granulocyte-colony stimulating factor), collected by leukapheresis and cryopreserved. After 2-3 weeks, high dose immunosuppression is given (cyclophosphamide 200 mg/kg plus rabbit antithymocyte globulin 4.5 mg/kg) and stem cells are thawed and injected intravenously. This procedure is performed in isolated rooms at the Bone Marrow Transplantation Unit of the School of Medicine of Ribeirão Preto, University of São Paulo, Brazil. Patients are discharged from the hospital after engraftment and closely followed up to 2 months after transplantation (with at least weekly outpatient visits) and continue the followup for 5 years after transplantation. Clinical, hematological, metabolical and immunological evaluations are performed to analyse the effect of the transplant in the disease and in the hematopoetic and immunologic systems of the body. 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Transplant arm | Experimental | Procedure: Immunosuppression and autologous stem cell transplantationThis is a single arm study. The intervention is immunosuppression and autologous stem cell transplantation. |
Who may qualify
- Ages
- 12 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 antibodies
- Less than 12 weeks 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 |
|---|---|---|
| Immunosuppression and autologous stem cell transplantationImmunosuppression and autologous stem cell transplantation: Mobilization of hematopoietic stem cells (HSC) with cyclophosphamide (2 g/m2) and granulocyte-colony stimulating factor (G-CSF, 10 ug/kg/d), followed by collection and cryopreservation of unselected HSC and conditioning with cyclophosphamide (200 mg/kg) plus rabbit anti-thymocyte globulin (ATG 4.5 mg/kg). | Procedure or surgery | Transplant arm |
Primary outcome
C-peptide levels
Time frame: Every 6 months
Stimulated C-peptide levels will be measured.
6 secondary outcomes
Transplant-related toxicity
Time frame: Every 6 months or when reported
Anti-GAD titres
Time frame: Every 6 months
Exogenous insulin dose
Time frame: Every 6 months
Hemoglobin A1C
Time frame: Every 6 months
Immunologic reconstitution parameters
Time frame: Yearly
Quality of Life
Time frame: Every year
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 Jan 2017.
- Background: PubMed 12849006Burt RK, Oyama Y, Traynor A, Kenyon NS. Hematopoietic stem cell therapy for type 1 diabetes: induction of tolerance and islet cell neogenesis. Autoimmun Rev. 2002 May;1(3):133-8. doi: 10.1016/s1568-9972(02)00033-2.
- Results publication: 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.
- Results publication: PubMed 19366777Couri CE, Oliveira MC, Stracieri AB, Moraes DA, Pieroni F, Barros GM, Madeira MI, Malmegrim KC, Foss-Freitas MC, Simoes BP, Martinez EZ, Foss MC, Burt RK, Voltarelli JC. C-peptide levels and insulin independence following autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA. 2009 Apr 15;301(15):1573-9. doi: 10.1001/jama.2009.470.
- Individual participant dataSharing planned: Undecided. IPD may be shared if the responsible investigators feel it may increase understanding, reliability and reproducibility of the present study.
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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.
Julio C Voltarelli, MD PhD principal investigator
University Hospital, School of Medicine of Ribeirão Preto, Brazil
Maria C Oliveira, MD PhD study chair
University Hospital, Ribeirão Preto Medical School, Brazil
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Immunosuppression and autologous stem cell transplantation in people with Type 1 Diabetes Mellitus, run by University of Sao Paulo at 1 site in Brazil.
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 Jan 2017. 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 Brazil. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
C-peptide levels (time frame: Every 6 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 NCT00315133, which also lists 3 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 Jan 2017.