Diabetes Mellitus, Type IPhase 2NCT00790439
Safety and Effectiveness of Low Molecular Weight Sulfated Dextran in Islet Transplantation After Kidney Transplant
A Phase 2 study testing Low Molecular Weight Sulfated Dextran, Heparin and Mycophenolate Mofetil in people with Diabetes Mellitus, Type I, run by National Institute of Allergy and Infectious Diseases (NIAID).
Trial summary
Type 1 diabetes mellitus (T1D) is an autoimmune disease in which the insulin-producing pancreatic beta cells are destroyed, resulting in poor blood sugar control. The purpose of this study is to assess the safety and effectiveness of low molecular weight sulfated dextran (LMW-SD) on post-transplant islet function in… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Diabetes Mellitus, Type I
- What is being tested?
- Low Molecular Weight Sulfated Dextran, Heparin and Mycophenolate Mofetil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jul 2008to Oct 2009
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects able to provide written informed consent and comply with study procedures
- Clinical history compatible with T1D and onset of disease at less than 40 years of age and insulin dependence for more than (>) 5 years at the time of enrollment; AND the sum of subject age and insulin-dependent diabetes duration is >=28
- Absent stimulated C-peptide (less than 0.3 ng/mL) 60 and 90 minutes post-mixed-meal tolerance test (MMTT)
- Subjects >6 months post renal (kidney) transplant, currently taking or willing to switch to appropriate maintenance immunosuppression
- Stable renal function and free of rejection for >=3 months prior to islet transplantation
- Standard medical treatment for >=3 months under the care of an experienced diabetologist and at the end of this period has had at least 1 severe hypoglycemic event OR a hemoglobin A1C (HbA1c) >7.2% OR reduced awareness of hypoglycemia manifest by a Clark score of >=4 in the last year prior to study entry
Who cannot join
- Known immunoglobulin E (IgE) mediated allergy to antibiotics used in islet culture medium
- Known hypersensitivity to dextran
- Measured glomerular filtration rate (GFR) using Iothalmate, 51Cr-EDTA, 99-technetium-DPTA, or iohexol of less than 40ml/min/1.73 m^2
- Proteinuria (albuminuria greater than 500 mg in 24 hours) of new onset since kidney transplantation
- Other (non-kidney) organ transplants except prior failed pancreatic graft
- Body mass index (BMI) >30 kg/m^2
Show all 29Show fewer
- Insulin requirement of >1.0 IU/kg/day
- Consistently abnormal liver function tests (aspartate aminotransferase(AST), alanine aminotransferase (ALT),alkaline phosphatase, or total bilirubin) of greater than 1.5 times the upper limit of normal for two consecutive measurements that are >2 weeks apart
- Untreated proliferative diabetic retinopathy
- History of hypercoagulability disorder or coagulopathy or International Normalized Ratio(INR) that is >1.5
- Activated Protein C Resistance (APC-R)
- Evidence by serologies and PCR of acute or chronic active Epstein-Barr Virus (EBV) infection OR no evidence by EBV serologies of prior EBV exposure
- Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin
- Known history of severe co-existing cardiac disease, characterized by any one of the following conditions:
- Recent myocardial infarction (<=6 months)
- Evidence of ischemia on functional cardiac exam <=last year
- Left ventricular ejection fraction <30%
- Active infections, unless treatment is not judged necessary by the investigators(including but not limited to mild skin and nail fungal infections)
- Active infection including hepatitis B, hepatitis C,human immunodeficiency virus (HIV), or pulmonary tuberculosis
- Subjects with active peptic ulcer disease, symptomatic gallstones or portal hypertension
- Acute or chronic pancreatitis
- Subjects who are pregnant or breastfeeding, or who intend to become pregnant
- Sexually-active females who are not: a) post-menopausal, b) surgically sterile, or c) using an acceptable method of contraception: oral contraceptives, Norplant, Depo-Provera, and barrier devices combined with spermicidal gel are acceptable; condoms used alone are not acceptable.
- Active alcohol or substance abuse
- Evidence of high-level sensitization (Panel Reactive Antibodies (PRA) >50%) or positive cross match or the known presence of anti-donor HLA class I antibodies
- Treatment with any anti-diabetic medication, other than insulin, <=4 weeks of enrollment
- Use of any investigational agents <=4 weeks of enrollment
- Receipt of live attenuated vaccine(s) <=2 months of enrollment
- Subjects with any condition or circumstance that in the opinion of the investigator would make it unsafe to undergo an islet transplantation
About this study
Official title: Open Randomized Multi-Center Study to Evaluate Safety and Efficacy of Low Molecular Weight Sulfated Dextran (LMW-SD) in Islet Transplantation After Kidney Transplantation (CIT-01B)
Type 1 diabetes mellitus (T1D) is an autoimmune disease in which the insulin-producing pancreatic beta cells are destroyed, resulting in poor blood sugar control. The purpose of this study is to assess the safety and effectiveness of low molecular weight sulfated dextran (LMW-SD) on post-transplant islet function in people with T1D who have responded to intensive insulin therapy and have received kidney transplants. This study is taking place in Uppsala and Stockholm, Sweden, and Oslo, Norway.
Read the detailed description
T1D is commonly treated with the administration of insulin, either by multiple insulin injections or by a continuous supply of insulin through a wearable pump. Insulin therapy allows long-term survival in individuals with T1D; however, it does not guarantee constant normal blood sugar control. Because of this, long-term type 1 diabetic survivors often develop vascular complications, such as diabetic retinopathy, an eye disease that can cause poor vision and blindness, and diabetic nephropathy, a kidney disease that can lead to kidney failure and thus kidney transplant. Some individuals with T1D develop hypoglycemia unawareness, a life-threatening condition that is not easily treatable with medication and is characterized by reduced or absent warning signals for hypoglycemia. For such individuals, pancreas or pancreatic islet transplantation are possible treatment options. Rejection of these islets by the recipient's immune system, however, can make the treatment ineffective. An immune response known as instant blood-mediated inflammatory reaction (IBMIR) results in the disruption of islet integrity and islet loss within an hour of transplantation. LMW-SD inhibits IBMIR by preventing the cascade that triggers it, when combined with pancreatic islets. The purpose of this study is to determine the safety and efficacy of LMW-SD improving the outcome of islet transplantation by preventing IBMIR.
Once a preparation of islets becomes available, participants will be randomly assigned to either the low molecular weight sulfated dextran (LMW-SD) Arm or to the Control Group/Standard of Care Arm. Participants in the LMW-SD Arm will receive LMW-SD before, with and for 5 hours after islet transplantation. Participants in the Control Group will receive heparin with the islet transplantation. All participants will also receive the oral medications, mycophenolate mofetil or sirolimus and tacrolimus or cyclosporine throughout the study. In addition, they will receive either intravenous daclizumab on the day of islet transplantation and at Week 2, 4, 6, and 8 or intravenous basiliximab on the day of islet transplantation and on Day 4. The islet transplantation will occur at the hospital and will be given via the portal vein. All participants will be eligible to receive second and third islet transplantation(s) if previous transplants fail. After each islet transplantation, study visits will occur on Days 1, 3, 7, 14, 21, 28, 75, and Months 6 and 12. At these visits, physical exams and blood collection will occur. At some visits urine collection will also occur.
- Conditions
- Diabetes Mellitus, Type I
- Being tested
- Low Molecular Weight Sulfated Dextran, Heparin, Mycophenolate Mofetil, Sirolimus, Tacrolimus
- Keywords
- Insulin dependence
- 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.
Low Molecular Weight Sulfated DextranDrug
Also called LMW-SD
Inhibitor of instant blood-mediated inflammatory reaction
HeparinDrug
Also called Heparin Sodium
Anticoagulant
Also called MMF, Mycophenolate, Mycophenolic Acid, CellCept
Cell proliferation inhibitor, Transplantation (immunosuppressive)
SirolimusDrug
Also called Rapamune
Cell proliferation inhibitor, immunologic (immunosuppressive)
TacrolimusDrug
Also called Hecoria
Calcineurin inhibitor
CyclosporineDrug
Also called Ciclosporin, GENGRAF® Capsules
Calcineurin inhibitor, immunosuppressant
DaclizumabDrug
Monoclonal IL-2 receptor blocker
BasiliximabDrug
Also called Simulect ®
Monoclonal IL-2 receptor blocker
Allogeneic Pancreatic Islet CellsBiological
| Study group | Role | What they receive |
|---|---|---|
| LMW-SD | Experimental | 18 participants randomized to immunosuppression with Low Molecular Weight Sulfated Dextran (LMW-SD) Receives: Drug: Low Molecular Weight Sulfated Dextran; Drug: Mycophenolate Mofetil; Drug: Sirolimus; Drug: Tacrolimus; Drug: Cyclosporine; Drug: Daclizumab; Drug: Basiliximab; Biological: Allogeneic Pancreatic Islet Cells |
| Control Group, Standard of Care | Active comparator | 18 participants randomized to immunosuppression without Low Molecular Weight Sulfated Dextran (LMW-SD) Receives: Drug: Heparin; Drug: Mycophenolate Mofetil; Drug: Sirolimus; Drug: Tacrolimus; Drug: Cyclosporine; Drug: Daclizumab; Drug: Basiliximab; Biological: Allogeneic Pancreatic Islet Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Level of Stimulated C-peptide at 90-minutes in Response to a Mixed-Meal Tolerance Test (MMTT)
Measured: 75 days following the first islet transplantation
Secondary outcomes (5)
Incidence and Severity of Adverse Events Related to the Islet Transplantation Procedure
Measured: 75 days and 365 days following the first islet transplantation
Incidence and Severity of Adverse Events Related to the Immunosuppression
Measured: 75 days and 365 days following the first islet transplantation
Incidence of Immune Sensitization Defined by Detecting Anti-HLA (Human Leukocyte Antigen) Antibodies not present prior to transplantation
Defined by detecting anti-HLA (Human Leukocyte Antigen) antibodies not present prior to transplantation
Measured: 75 days and 365 days following the first islet transplantation
Incidence of a Change in the Immunosuppression Drug Regimen
Measured: 75 days and 365 days following the first islet transplantation
Incidence of Worsening Retinopathy
As assessed by change in retinal photography from pre-transplant to 365 days following the first islet transplantation
Measured: 365 days following the first islet transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2008 (estimated)
- Study startJul 2008
- Primary completionOct 2009
- Study completionOct 2009
Why it stopped: Due to funding limitations
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus, Type IStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Olle Korsgren, MD, Principal investigator, Department of Oncology, Radiology, and Clinical Immunology, Rudbeck Laboratory, Uppsala University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00790439
- Sponsor's protocol ID
- DAIT CIT-01B
- Other IDs
- CIT-01B
- Status last verified
- Jun 2014
- First submitted
- 10 Nov 2008
- Last updated
- 12 Jun 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Randomized Multi-Center Study to Evaluate Safety and Efficacy of Low Molecular Weight Sulfated Dextran (LMW-SD) in Islet Transplantation After Kidney Transplantation (CIT-01B)
- ClinicalTrials.gov ID
- NCT00790439
- Acronym / sponsor ID
- DAIT CIT-01B
- Conditions
- Diabetes Mellitus, Type I
- Keywords
- Insulin dependence
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Due to funding limitations
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Jul 2008
- Primary completion
- Oct 2009 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 13 Nov 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.
Type 1 diabetes mellitus (T1D) is an autoimmune disease in which the insulin-producing pancreatic beta cells are destroyed, resulting in poor blood sugar control. The purpose of this study is to assess the safety and effectiveness of low molecular weight sulfated dextran (LMW-SD) on post-transplant islet function in people with T1D who have responded to intensive insulin therapy and have received kidney transplants. This study is taking place in Uppsala and Stockholm, Sweden, and Oslo, Norway.
Detailed description
T1D is commonly treated with the administration of insulin, either by multiple insulin injections or by a continuous supply of insulin through a wearable pump. Insulin therapy allows long-term survival in individuals with T1D; however, it does not guarantee constant normal blood sugar control. Because of this, long-term type 1 diabetic survivors often develop vascular complications, such as diabetic retinopathy, an eye disease that can cause poor vision and blindness, and diabetic nephropathy, a kidney disease that can lead to kidney failure and thus kidney transplant. Some individuals with T1D develop hypoglycemia unawareness, a life-threatening condition that is not easily treatable with medication and is characterized by reduced or absent warning signals for hypoglycemia. For such individuals, pancreas or pancreatic islet transplantation are possible treatment options. Rejection of these islets by the recipient's immune system, however, can make the treatment ineffective. An immune response known as instant blood-mediated inflammatory reaction (IBMIR) results in the disruption of islet integrity and islet loss within an hour of transplantation. LMW-SD inhibits IBMIR by preventing the cascade that triggers it, when combined with pancreatic islets. The purpose of this study is to determine the safety and efficacy of LMW-SD improving the outcome of islet transplantation by preventing IBMIR.
Once a preparation of islets becomes available, participants will be randomly assigned to either the low molecular weight sulfated dextran (LMW-SD) Arm or to the Control Group/Standard of Care Arm. Participants in the LMW-SD Arm will receive LMW-SD before, with and for 5 hours after islet transplantation. Participants in the Control Group will receive heparin with the islet transplantation. All participants will also receive the oral medications, mycophenolate mofetil or sirolimus and tacrolimus or cyclosporine throughout the study. In addition, they will receive either intravenous daclizumab on the day of islet transplantation and at Week 2, 4, 6, and 8 or intravenous basiliximab on the day of islet transplantation and on Day 4. The islet transplantation will occur at the hospital and will be given via the portal vein. All participants will be eligible to receive second and third islet transplantation(s) if previous transplants fail. After each islet transplantation, study visits will occur on Days 1, 3, 7, 14, 21, 28, 75, and Months 6 and 12. At these visits, physical exams and blood collection will occur. At some visits urine collection will also occur.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LMW-SD | Experimental | Drug: Low Molecular Weight Sulfated Dextran, Drug: Mycophenolate Mofetil, Drug: Sirolimus, Drug: Tacrolimus, Drug: Cyclosporine, Drug: Daclizumab, Drug: Basiliximab, Biological: Allogeneic Pancreatic Islet Cells18 participants randomized to immunosuppression with Low Molecular Weight Sulfated Dextran (LMW-SD) |
| Control Group, Standard of Care | Active comparator | Drug: Heparin, Drug: Mycophenolate Mofetil, Drug: Sirolimus, Drug: Tacrolimus, Drug: Cyclosporine, Drug: Daclizumab, Drug: Basiliximab, Biological: Allogeneic Pancreatic Islet Cells18 participants randomized to immunosuppression without Low Molecular Weight Sulfated Dextran (LMW-SD) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Subjects able to provide written informed consent and comply with study procedures
- Clinical history compatible with T1D and onset of disease at less than 40 years of age and insulin dependence for more than (>) 5 years at the time of enrollment; AND the sum of subject age and insulin-dependent diabetes duration is >=28
- Absent stimulated C-peptide (less than 0.3 ng/mL) 60 and 90 minutes post-mixed-meal tolerance test (MMTT)
- Subjects >6 months post renal (kidney) transplant, currently taking or willing to switch to appropriate maintenance immunosuppression
- Stable renal function and free of rejection for >=3 months prior to islet transplantation
Key exclusion criteria (29 listed)
- Known immunoglobulin E (IgE) mediated allergy to antibiotics used in islet culture medium
- Known hypersensitivity to dextran
- Measured glomerular filtration rate (GFR) using Iothalmate, 51Cr-EDTA, 99-technetium-DPTA, or iohexol of less than 40ml/min/1.73 m^2
- Proteinuria (albuminuria greater than 500 mg in 24 hours) of new onset since kidney transplantation
- Other (non-kidney) organ transplants except prior failed pancreatic graft
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 |
|---|---|---|
| Low Molecular Weight Sulfated DextranAlso: LMW-SDInhibitor of instant blood-mediated inflammatory reaction | Drug | LMW-SD |
| HeparinAlso: Heparin SodiumAnticoagulant | Drug | Control Group, Standard of Care |
| Mycophenolate MofetilAlso: MMF, Mycophenolate, Mycophenolic Acid, CellCeptCell proliferation inhibitor, Transplantation (immunosuppressive) | Drug | Control Group, Standard of Care, LMW-SD |
| SirolimusAlso: RapamuneCell proliferation inhibitor, immunologic (immunosuppressive) | Drug | Control Group, Standard of Care, LMW-SD |
| TacrolimusAlso: HecoriaCalcineurin inhibitor | Drug | Control Group, Standard of Care, LMW-SD |
| CyclosporineAlso: Ciclosporin, GENGRAF® CapsulesCalcineurin inhibitor, immunosuppressant | Drug | Control Group, Standard of Care, LMW-SD |
| DaclizumabMonoclonal IL-2 receptor blocker | Drug | Control Group, Standard of Care, LMW-SD |
| BasiliximabAlso: Simulect ®Monoclonal IL-2 receptor blocker | Drug | Control Group, Standard of Care, LMW-SD |
| Allogeneic Pancreatic Islet Cells | Biological | Control Group, Standard of Care, LMW-SD |
Primary outcome
Level of Stimulated C-peptide at 90-minutes in Response to a Mixed-Meal Tolerance Test (MMTT)
Time frame: 75 days following the first islet transplantation
5 secondary outcomes
Incidence and Severity of Adverse Events Related to the Islet Transplantation Procedure
Time frame: 75 days and 365 days following the first islet transplantation
Incidence and Severity of Adverse Events Related to the Immunosuppression
Time frame: 75 days and 365 days following the first islet transplantation
Incidence of Immune Sensitization Defined by Detecting Anti-HLA (Human Leukocyte Antigen) Antibodies not present prior to transplantation
Time frame: 75 days and 365 days following the first islet transplantation
Incidence of a Change in the Immunosuppression Drug Regimen
Time frame: 75 days and 365 days following the first islet transplantation
Incidence of Worsening Retinopathy
Time frame: 365 days following the first islet transplantation
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 12 Jun 2014.
- Click here for the Clinical Islet Transplantation Consortium Web siteLink provided by the sponsor.
- National Institute of Allergy and Infectious Diseases (NIAID)Link provided by the sponsor.
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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.
Olle Korsgren, MD principal investigator
Department of Oncology, Radiology, and Clinical Immunology, Rudbeck Laboratory, Uppsala University Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Low Molecular Weight Sulfated Dextran, Heparin and Mycophenolate Mofetil in people with Diabetes Mellitus, Type I, run by National Institute of Allergy and Infectious Diseases (NIAID).
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 6 inclusion and 29 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 12 Jun 2014. 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 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 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?
Level of Stimulated C-peptide at 90-minutes in Response to a Mixed-Meal Tolerance Test (MMTT) (time frame: 75 days following the first islet transplantation). 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 12 Jun 2014.