Diabetes Mellitus, Type 1Phase 1/2NCT01285934
Hematopoietic Stem Cell Support Versus Insulin in T1D
A Phase 1/2 study testing Autologous Hematopoietic Stem Cell Transplantation and intensive insulin therapy in people with Diabetes Mellitus, Type 1, run by Northwestern University.
Trial summary
Type 1 diabetes mellitus (T1D) results from immune-mediated destruction of insulin-producing islet cells. The loss of islet cells is traditionally treated with insulin therapy and in some cases pancreas or islet cell transplantation. Another approach would be to preserve islet cell mass before it is irreversibly lost. Read more about this study
- Who is it for?
- Ages 16 to 35 years
- Conditions the study is for
- Diabetes Mellitus, Type 1
- What is being tested?
- Autologous Hematopoietic Stem Cell Transplantation and intensive insulin therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jan 2009to Aug 2015
- 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 16 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Ages 16 to 35 years old
- A diagnosis of type 1 diabetes by hyperglycemia and at least 1 antibody to islet cell autoantigen: GAD, IAA, ICA, IA-2, or Slc30A8
- Fasting C-peptide > 0.20 nmol / liter
- Enrollment within 5 months of T1D diagnosis
- Eligible patients must be referred to a fertility / reproductive endocrinologist and have written documentation of medical counseling advising patients about the risk of infertility and the possible options of sperm and oocyte banking before enrollment.
Who cannot join
- HIV positive
- Patients in the honeymoon phase not taking insulin
- Hepatitis A, B, or C positive
- On corticosteroids or other immune suppressive medications
- History of diabetic ketoacidosis
- Ongoing malignancy except localized treated basal cell or squamous skin cancer.
Show all 20Show fewer
- History of cardiac disease or congestive heart failure or ventricular tachycardia or abnormal dobutamine cardiac echocardiogram
- Positive pregnancy test, inability or unwillingness to pursue effective means of birth control, failure to willingly accept or comprehend irreversible sterility as a potential side effect of therapy.
- Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible.
- DLCO < 60% of predicted
- Resting LVEF < 45%
- Creatinine > 1.5 mg/dl
- Known hypersensitivity to E Coli derived proteins.
- Transaminases greater than 2 times normal
- Positive tuberculosis skin test
- Any active infection
- Any co-morbid illness that in the opinion of the investigator would jeopardize the ability of the subject to tolerate the study.
- Failure to collect at least 2.0 x 106 CD34+ cells/kg
- History of alcohol or illicit drug abuse
- Unwilling to be compliant with change in life-style-diet and exercise
About this study
Official title: A Trial of High Dose Immunosuppression and Autologous Hematopoietic Stem Cell Support Versus Intensive Insulin Therapy in Adults With Early Onset Type I Diabetes Mellitus
Type 1 diabetes mellitus (T1D) results from immune-mediated destruction of insulin-producing islet cells. The loss of islet cells is traditionally treated with insulin therapy and in some cases pancreas or islet cell transplantation. Another approach would be to preserve islet cell mass before it is irreversibly lost. Previous trials using immune suppression within 6 weeks of T1D onset have demonstrated diminished exogenous insulin requirements compared to untreated controls. In our prior phase I non-randomized study, by extending immune suppression to the point of immune ablation / immune reset with autologous HSC support, several patients with new onset T1D have maintained an insulin-free, drug free remissions for more than 4 years. Although these results appear highly promising, it may be argued that our results are mitigated by the documented honeymoon effect following T1D, that is by a normal transient insulin free interval occurring after disease onset in some patients. The goal of this trial is to extend this phase I study of new onset T1D to clarify whether our post transplant insulin free interval is due to treatment intervention (transplant) or a result of a normally occurring "insulin free honeymoon period". Both groups will receive identical change of life style (i.e. diet, exercise) education.
Read the detailed description
Eligible patients will have type 1 diabetes (aged ≥ 18 years old) within five months of disease diagnosis, and a positive antibody to an islet cell autoantigen, and fasting C-peptide > 0.2 nmol/l. Hematopoietic stem cells will be mobilized with cyclophosphamide (2.0 g/m2) and granulocyte colony-stimulating factor (10 g/kg/day) collected from peripheral blood by leukoapheresis and cryopreserved. HSC will injected IV after conditioning with cyclophosphamide (200 mg/kg) divided 50 mg/kg on day -5, -4, -3, -2, and rabbit antithymocyte globulin (4.5 mg/kg) divided 0.5 mg/kg day-5, and 1.0 mg/kg day -4, -3-, -2, -1. Rituxan (500mg) IV will be given on days -6 and +1. The control arm will receive either continuous subcutaneous insulin infusion (CSII) or intensive subcutaneous insulin therapy with multiple insulin injections (at least 4/day) utilizing a long acting background insulin and pre-meal rapid acting insulin. The main outcome measure will be: fasting C-peptide. Other outcome measures will include: daily exogenous insulin requirements, serum levels of hemoglobin A1c, area under the curve (AUC) C-peptide levels during mixed meal tolerance test, islet cell autoantigen antibody titers, and quality of life (QOL) short form 36 (SF-36) questionnaire.
- Conditions
- Diabetes Mellitus, Type 1
- Being tested
- Autologous Hematopoietic Stem Cell Transplantation, intensive insulin therapy
- 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.
Autologous Hematopoietic Stem Cell TransplantationBiological
All participants randomized to the transplant arm wil undergo Autologous Hematopoietic Stem Cell Transplantation
intensive insulin therapyDrug
Also called IIT
The control arm will be either CSII via an insulin pump or intensive subcutaneous insulin therapy with multiple insulin injections (at least 4/day) utilizing a long acting background insulin and pre-meal rapid acting insulin.
| Study group | Role | What they receive |
|---|---|---|
| Hematopoietic Stem Cell Transplantation | Experimental | Patients who meet eligibility and have completed pre-HSCT testing in section 7.0 (study parameters) may be enrolled in the transplant arm and will undergo an Autologous Hematopoietic Stem Cell Transplantation Receives: Biological: Autologous Hematopoietic Stem Cell Transplantation |
| control arm of intensive insulin therapy | Other | The control arm of intensive insulin therapy (IIT) will enroll all patients who meet eligibility but decline HSCT or whose insurance does not approve payment for HSCT before expiration of eligibility (within 5 months of disease onset) Receives: Drug: intensive insulin therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
C-peptide
C-peptide (fasting and every 30 minutes during 2 hour mixed meal tolerance test
Measured: Every 6 months for 5 years
Secondary outcomes (3)
Insulin dose
Insulin dose, recorded as daily insulin dose in IU/Kg/day
Measured: 5 years
Serum levels of hemoglobin A1c
Measured: 5 years
Stimulated C-peptide levels during mixed meal tolerance test
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2011 (estimated)
- Study startJan 2009
- Primary completionAug 2015
- Study completionAug 2015
Why it stopped: No participant enrolled
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus, Type 1Studies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Sao Paulo General Hospital
- Responsible party
- Principal investigator, Richard Burt, MD, Northwestern University
- Investigators
- Richard Burt, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01285934
- Sponsor's protocol ID
- Diabetes2008
- Status last verified
- Mar 2015
- First submitted
- 27 Jan 2011
- Last updated
- 21 Aug 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Trial of High Dose Immunosuppression and Autologous Hematopoietic Stem Cell Support Versus Intensive Insulin Therapy in Adults With Early Onset Type I Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT01285934
- Acronym / sponsor ID
- Diabetes2008
- Conditions
- Diabetes Mellitus, Type 1
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No participant enrolled
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- University of Sao Paulo General Hospital
- Study start
- Jan 2009
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 28 Jan 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 mellitus (T1D) results from immune-mediated destruction of insulin-producing islet cells. The loss of islet cells is traditionally treated with insulin therapy and in some cases pancreas or islet cell transplantation. Another approach would be to preserve islet cell mass before it is irreversibly lost. Previous trials using immune suppression within 6 weeks of T1D onset have demonstrated diminished exogenous insulin requirements compared to untreated controls. In our prior phase I non-randomized study, by extending immune suppression to the point of immune ablation / immune reset with autologous HSC support, several patients with new onset T1D have maintained an insulin-free, drug free remissions for more than 4 years. Although these results appear highly promising, it may be argued that our results are mitigated by the documented honeymoon effect following T1D, that is by a normal transient insulin free interval occurring after disease onset in some patients. The goal of this trial is to extend this phase I study of new onset T1D to clarify whether our post transplant insulin free interval is due to treatment intervention (transplant) or a result of a normally occurring "insulin free honeymoon period". Both groups will receive identical change of life style (i.e. diet, exercise) education.
Detailed description
Eligible patients will have type 1 diabetes (aged ≥ 18 years old) within five months of disease diagnosis, and a positive antibody to an islet cell autoantigen, and fasting C-peptide > 0.2 nmol/l. Hematopoietic stem cells will be mobilized with cyclophosphamide (2.0 g/m2) and granulocyte colony-stimulating factor (10 g/kg/day) collected from peripheral blood by leukoapheresis and cryopreserved. HSC will injected IV after conditioning with cyclophosphamide (200 mg/kg) divided 50 mg/kg on day -5, -4, -3, -2, and rabbit antithymocyte globulin (4.5 mg/kg) divided 0.5 mg/kg day-5, and 1.0 mg/kg day -4, -3-, -2, -1. Rituxan (500mg) IV will be given on days -6 and +1. The control arm will receive either continuous subcutaneous insulin infusion (CSII) or intensive subcutaneous insulin therapy with multiple insulin injections (at least 4/day) utilizing a long acting background insulin and pre-meal rapid acting insulin. The main outcome measure will be: fasting C-peptide. Other outcome measures will include: daily exogenous insulin requirements, serum levels of hemoglobin A1c, area under the curve (AUC) C-peptide levels during mixed meal tolerance test, islet cell autoantigen antibody titers, and quality of life (QOL) short form 36 (SF-36) questionnaire.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hematopoietic Stem Cell Transplantation | Experimental | Biological: Autologous Hematopoietic Stem Cell TransplantationPatients who meet eligibility and have completed pre-HSCT testing in section 7.0 (study parameters) may be enrolled in the transplant arm and will undergo an Autologous Hematopoietic Stem Cell Transplantation |
| control arm of intensive insulin therapy | Other | Drug: intensive insulin therapyThe control arm of intensive insulin therapy (IIT) will enroll all patients who meet eligibility but decline HSCT or whose insurance does not approve payment for HSCT before expiration of eligibility (within 5 months of disease onset) |
Who may qualify
- Ages
- 16 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Ages 16 to 35 years old
- A diagnosis of type 1 diabetes by hyperglycemia and at least 1 antibody to islet cell autoantigen: GAD, IAA, ICA, IA-2, or Slc30A8
- Fasting C-peptide > 0.20 nmol / liter
- Enrollment within 5 months of T1D diagnosis
- Eligible patients must be referred to a fertility / reproductive endocrinologist and have written documentation of medical counseling advising patients about the risk of infertility and the possible options of sperm and oocyte banking before enrollment.
Key exclusion criteria (20 listed)
- HIV positive
- Patients in the honeymoon phase not taking insulin
- Hepatitis A, B, or C positive
- On corticosteroids or other immune suppressive medications
- History of diabetic ketoacidosis
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 |
|---|---|---|
| Autologous Hematopoietic Stem Cell TransplantationAll participants randomized to the transplant arm wil undergo Autologous Hematopoietic Stem Cell Transplantation | Biological | Hematopoietic Stem Cell Transplantation |
| intensive insulin therapyAlso: IITThe control arm will be either CSII via an insulin pump or intensive subcutaneous insulin therapy with multiple insulin injections (at least 4/day) utilizing a long acting background insulin and pre-meal rapid acting insulin. | Drug | control arm of intensive insulin therapy |
Primary outcome
C-peptide
Time frame: Every 6 months for 5 years
C-peptide (fasting and every 30 minutes during 2 hour mixed meal tolerance test
3 secondary outcomes
Insulin dose
Time frame: 5 years
Serum levels of hemoglobin A1c
Time frame: 5 years
Stimulated C-peptide levels during mixed meal tolerance test
Time frame: 5 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2015.
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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.
Richard Burt, MD principal investigator
Northwestern University
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Autologous Hematopoietic Stem Cell Transplantation and intensive insulin therapy in people with Diabetes Mellitus, Type 1, run by Northwestern University.
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 5 inclusion and 20 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: withdrawn, as of the sponsor's last update on 21 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
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 was withdrawn before enrolling participants, so there are no results.
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 (time frame: Every 6 months for 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Aug 2015.