Diabetes Mellitus, Type IPhase 2NCT00789308
Safety and Effectiveness of Low Molecular Weight Sulfated Dextran in Islet Transplantation
A Phase 2 study testing Low Molecular Weight Sulfated Dextran (LMW-SD), Heparin and CellCept® (Mycophenolate mofetil) OR Rapamune® (Sirolimus) in people with Diabetes Mellitus, Type I, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in 2 countries.
Trial summary
Type 1 diabetes 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 type… 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 (LMW-SD), Heparin and CellCept® (Mycophenolate mofetil) OR Rapamune® (Sirolimus)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 11 Jul 2008to 21 Aug 2014
- 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
- Mentally stable and able to comply with study procedures;
- Clinical history compatible with type 1 diabetes, with:
- onset of disease at less than 40 years of age,
- insulin dependence for at least 5 years at study entry, and
- sum of age and insulin-dependent diabetes duration of at least 28.
- Absent stimulated C-peptide (less than 0.3 ng/ml) 60 and 90 minutes post-mixed-meal tolerance test;
Show all 12Show fewer
- Involvement of intensive diabetes management, defined as:
- Self-monitoring of glucose values no less than a mean of three times each day, averaged over each week,
- Administration of three or more insulin injections each day or insulin pump therapy,
- Under the direction of an endocrinologist, diabetologist, or diabetes specialist, with at least three clinical evaluations during the past 12 months.
- At least one episode of severe hypoglycemia in the past 12 months, defined as an event with symptoms compatible with hypoglycemia in which the individual required assistance of another person and which was associated with either a blood glucose level less than 54 mg/dl or prompt recovery after an oral carbohydrate, intravenous glucose, or glucagon administration; and
- Reduced awareness of hypoglycemia OR marked glycemic lability OR a composite of a Clarke score of 3 or more or a HYPO score greater or equal to the 75th percentile in the 12 months prior to randomization.
Who cannot join
- Known IgE mediated allergy to antibiotics used in the culture medium;
- Known hypersensitivity to dextran;
- Body mass index (BMI) greater than 30 kg/m^2;
- Insulin requirement of more than 1.0 IU/kg/day;
- HbA1c greater than 10%;
- Untreated proliferative diabetic retinopathy;
Show all 35Show fewer
- Systolic blood pressure higher than 160 mmHg or diastolic blood pressure higher than 100 mmHg;
- Measured glomerular filtration rate (GFR) using 51Cr-EDTA, 99technetium-DPTA, or iohexol of less than 80 ml/min/1.73m^2;
- Presence or history of macroalbuminuria (greater than 300 mg/g creatinine);
- Presence or history of panel-reactive anti-HLA antibody levels greater than 20% by flow cytometry;
- Pregnant, breastfeeding, or unwilling to use effective contraception throughout the study and for 4 months after study completion;
- Active infection, including hepatitis B virus, hepatitis C virus, HIV, or tuberculosis;
- Negative for Epstein-Barr virus by IgG determination;
- History of malignancy with exception of completely resected squamous or basal cell carcinoma of the skin;
- Known active alcohol or substance abuse;
- Baseline Hgb below the lower limits of normal, lymphopenia, neutropenia, or thrombocytopenia;
- Activated protein C resistance (APC-R);
- Any coagulopathy or individuals with an INR greater than 1.5;
- Severe coexisting cardiac disease, characterized by any one of the following conditions:
- Heart attack within the last 6 months,
- Evidence of ischemia on functional heart exam within the year prior to study entry, or
- Left ventricular ejection fraction less than 30%.
- Persistent elevation of liver function tests at the time of study entry;
- Acute or chronic pancreatitis;
- Active peptic ulcer disease, symptomatic gallstones, or a history of portal hypertension;
- Severe unremitting diarrhea, vomiting, or other gastrointestinal disorders that could interfere with the ability to absorb oral medications;
- Currently receiving treatment for a medical condition that requires chronic use of systemic steroids;
- Treatment with any antidiabetic medication other than insulin, within 4 weeks prior to study entry;
- Use of any investigational medications within the past 4 weeks;
- Received a live attenuated vaccine within the past 2 months;
- Treatment with any immunosuppressive regimen at time of study entry;
- Previous islet transplant;
- Previous pancreas transplant.
- --Note: Participants who had a pancreas transplant more than 6 months prior to study entry that failed within the first week due to thrombosis, followed by surgical removal of the transplanted pancreas, are not excluded.
- Or any medical condition that, in the opinion of the investigator, might interfere with safe participation.
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Sweden2 sites
Karolinska University Hospital
Stockholm
Uppsala University Hospital
Uppsala
About this study
Official title: Open Randomized Mult-Center Study to Evaluate Safety and Efficacy of Low Molecular Weight Sulfated Dextran in Islet Transplantation (CIT-01)
Type 1 diabetes 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 type 1 diabetes who have responded to intensive insulin therapy.
Read the detailed description
Type I diabetes, also known as insulin-dependent diabetes, is a chronic disease in which the pancreas produces insufficient insulin to properly regulate blood sugar levels. Hypoglycemia, or low blood sugar, and hyperglycemia, or high blood sugar, can lead to significant complications in people with type 1 diabetes. Intensive insulin therapy has been shown to reduce the risk of chronic complications in people who achieve near normalization of glycemia. However, this therapy is labor intensive, difficult to implement, and associated with an increased frequency of severe hypoglycemia. Transplantation of islets from a healthy pancreas has been successful in restoring normal blood sugar levels and has led to initial insulin independence in people with type 1 diabetes. 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 transfusion. 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 given with islet transfusion and post-transfusion along with immunosuppressive therapy, including mycophenolate mofetil or sirolimus, tacrolimus or cyclosporine, and thymoglobulin or basiliximab, on the success of islet transplantation in people with type 1 diabetes.
This study will last for 1 year after the final islet transplant. Participants may receive up to 3 islet transplants while participating in this study. Participants eligible for this study will have clinic visits every 6 months. Once a preparation of islets becomes available, participants will be randomly assigned to Arm 1 or Arm 2. Participants in Arm 1 will receive LMW-DS during and for 5 hours after infusion. Participants in Arm 2 will receive heparin at the time of infusion. In addition, all participants will receive anticoagulation prophylaxis agents consisting of Klexzane® (Enoxaparinsodium) and Trombyl® or Albyl-E® (Acetylsalicylic acid). All participants will also receive the oral immunosuppression medications consisting of mycophenolate mofetil or sirolimus and tacrolimus or cyclosporine throughout the study. In addition, they will receive intravenous thymoglobulin on days -2, -1, day 0 (transplant), +1, and +2 for the first transplant or intravenous basiliximab at the time of transplant and on Day 4 for the second and third transplant. Enbrel® (Etanercept) will be given to all participants for anti-inflammatory therapy. Islet infusions will occur at the hospital and will be given intravenously. Participants will be eligible to receive second and third islet infusions if previous infusions fail and they continue to meet the eligibility criteria. After each infusion, study visits will occur on Days 1, 3, 7, 14, 21, 28, and 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 (LMW-SD), Heparin, CellCept® (Mycophenolate mofetil) OR Rapamune® (Sirolimus), Prograf® (Tacrolimus) OR Cyclosporine, Thymoglobulin® (Anti-thymocyte Globulin) - at first transplant
- 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 Dextran (LMW-SD)Drug
Inhibitor of IBMIR
HeparinDrug
Anticoagulation
CellCept® (Mycophenolate mofetil) OR Rapamune® (Sirolimus)Drug
Cell proliferation inhibitor
Prograf® (Tacrolimus) OR CyclosporineDrug
Calcineurin inhibitor
Thymoglobulin® (Anti-thymocyte Globulin) - at first transplantDrug
Simulect® (Basiliximab) - at 2nd or 3rd transplantDrug
Monoclonal IL-2 receptor blocker
Klexane® (Enoxaparinsodium)Drug
Anticoagulation Prophylaxis
Trombyl® or Albyl-E® (Acetylsalicylicacid- ASA)Drug
Anticoagulation Prophylaxis
Enbrel® (Etanercept)Drug
Anti-Inflammatory Therapy
| Study group | Role | What they receive |
|---|---|---|
| Standard of Care | Active comparator | 18 participants randomized to protocol immunosuppression (Daclizumab OR Basiliximab; Tacrolimus OR Cyclosporine; Mycophenolate Mofetil OR Sirolimus; and heparin) without LMW-DS Receives: Drug: Heparin; Drug: CellCept® (Mycophenolate mofetil) OR Rapamune® (Sirolimus); Drug: Prograf® (Tacrolimus) OR Cyclosporine; Drug: Thymoglobulin® (Anti-thymocyte Globulin) - at first transplant; Drug: Simulect® (Basiliximab) - at 2nd or 3rd transplant; Drug: Klexane® (Enoxaparinsodium); Drug: Trombyl® or Albyl-E® (Acetylsalicylicacid- ASA); Drug: Enbrel® (Etanercept) |
| LMW-DS | Experimental | 18 participants randomized to protocol immunosuppression (Daclizumab OR Basiliximab; Tacrolimus OR Cyclosporine; Mycophenolate Mofetil OR Sirolimus; and heparin) and LMW-DS Receives: Drug: Low Molecular Weight Sulfated Dextran (LMW-SD); Drug: CellCept® (Mycophenolate mofetil) OR Rapamune® (Sirolimus); Drug: Prograf® (Tacrolimus) OR Cyclosporine; Drug: Thymoglobulin® (Anti-thymocyte Globulin) - at first transplant; Drug: Simulect® (Basiliximab) - at 2nd or 3rd transplant; Drug: Klexane® (Enoxaparinsodium); Drug: Trombyl® or Albyl-E® (Acetylsalicylicacid- ASA); Drug: Enbrel® (Etanercept) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Level of stimulated c-peptide at 90-minute derived from the mixed-meal tolerance test (MMTT)
Measured: At 70 to 80 days after first islet transfusion
Secondary outcomes (19)
Number of participants who achieve and maintain a 7.0% HbA1c level
Measured: Throughout Study
Number of severe hypoglycemic events
Measured: Throughout study
Percent reduction in insulin requirements
Measured: At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion
Ryan hypoglycemia severity score ( HYPO) score
Measured: : At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion
Proportion of participants with full graft function
Measured: At 70 to 80 days after first islet transfusion and after the final islet infusion
C-peptide to glucose creatinine ratio
Measured: At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion
Proportion of participants receiving a second islet infusion and proportion of participants receiving a third islet transfusion
Measured: At 70 to 80 days after first islet transfusion and after the final islet infusion
Incidence and severity of adverse events related to islet infusion procedure
Measured: At 70 to 80 days and 350 to 379 days after the first islet transfusion
Incidence of worsening retinopathy
Measured: At 350 to 379 days after the first islet transfusion
HbA1c level
Measured: At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion
Mean amplitude of glycemic excursions (MAGE)
Measured: At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion
Glycemic lability index (LI)
Measured: At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion
Clarke hypoglycemia awareness score
Measured: At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion
Basal (fasting) and 90-minute glucose and c-peptide derived from MMTT
Measured: : At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion
Beta-score
Measured: At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion
Acute insulin response to glucose, insulin sensitivity, and disposition index derived from the insulin-modified frequently-sampled intravenous glucose tolerance (FSIGT) test,
Measured: At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion
Glucose variability and hypoglycemic duration derived from continuous glucose monitoring system(CGMS)
Measured: At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion
Incidence of a change in the immunosuppression drug regimen
Measured: At 70 to 80 days and 350 to 379 days after the first islet transfusion
Incidence of immune sensitization defined by detecting anti-HLA antibodies not present prior to transplantation
Measured: At 70 to 80 days and 350 to 379 days after the first islet transfusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2008 (estimated)
- Study start11 Jul 2008
- Primary completionJul 2013
- Study completion21 Aug 2014
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 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
- 24 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Clinical Islet Transplantation Consortium
- Responsible party
- Sponsor
- Investigators
- Olle Korsgren, MD, Principal investigator, Uppsala University HospitalTorbjörn Lundgren, MD, Study chair, Karolinska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00789308
- Sponsor's protocol ID
- DAIT CIT-01
- Other IDs
- CIT-01, 2008-001210-25, 2008
- Status last verified
- Sep 2021
- First submitted
- 10 Nov 2008
- Last updated
- 28 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: The plan is to share data upon completion of the study in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
Publications
von Zur-Muhlen B, Lundgren T, Bayman L, Berne C, Bridges N, Eggerman T, Foss A, Goldstein J, Jenssen T, Jorns C, Morrison Y, Ryden M, Schwieger T, Tufveson G, Nilsson B, Korsgren O. Open Randomized Multicenter Study to Evaluate Safety and Efficacy of Low Molecular Weight Sulfated Dextran in Islet Transplantation. Transplantation. 2019 Mar;103(3):630-637. doi: 10.1097/TP.0000000000002425.
PubMed 30211831
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Randomized Mult-Center Study to Evaluate Safety and Efficacy of Low Molecular Weight Sulfated Dextran in Islet Transplantation (CIT-01)
- ClinicalTrials.gov ID
- NCT00789308
- Acronym / sponsor ID
- DAIT CIT-01
- Conditions
- Diabetes Mellitus, Type I
- Keywords
- Insulin dependence
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 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), Clinical Islet Transplantation Consortium
- Study start
- 11 Jul 2008 (actual)
- Primary completion
- Jul 2013 (actual)
- Study completion
- 21 Aug 2014 (actual)
- First posted
- 11 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 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 type 1 diabetes who have responded to intensive insulin therapy.
Detailed description
Type I diabetes, also known as insulin-dependent diabetes, is a chronic disease in which the pancreas produces insufficient insulin to properly regulate blood sugar levels. Hypoglycemia, or low blood sugar, and hyperglycemia, or high blood sugar, can lead to significant complications in people with type 1 diabetes. Intensive insulin therapy has been shown to reduce the risk of chronic complications in people who achieve near normalization of glycemia. However, this therapy is labor intensive, difficult to implement, and associated with an increased frequency of severe hypoglycemia. Transplantation of islets from a healthy pancreas has been successful in restoring normal blood sugar levels and has led to initial insulin independence in people with type 1 diabetes. 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 transfusion. 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 given with islet transfusion and post-transfusion along with immunosuppressive therapy, including mycophenolate mofetil or sirolimus, tacrolimus or cyclosporine, and thymoglobulin or basiliximab, on the success of islet transplantation in people with type 1 diabetes.
This study will last for 1 year after the final islet transplant. Participants may receive up to 3 islet transplants while participating in this study. Participants eligible for this study will have clinic visits every 6 months. Once a preparation of islets becomes available, participants will be randomly assigned to Arm 1 or Arm 2. Participants in Arm 1 will receive LMW-DS during and for 5 hours after infusion. Participants in Arm 2 will receive heparin at the time of infusion. In addition, all participants will receive anticoagulation prophylaxis agents consisting of Klexzane® (Enoxaparinsodium) and Trombyl® or Albyl-E® (Acetylsalicylic acid). All participants will also receive the oral immunosuppression medications consisting of mycophenolate mofetil or sirolimus and tacrolimus or cyclosporine throughout the study. In addition, they will receive intravenous thymoglobulin on days -2, -1, day 0 (transplant), +1, and +2 for the first transplant or intravenous basiliximab at the time of transplant and on Day 4 for the second and third transplant. Enbrel® (Etanercept) will be given to all participants for anti-inflammatory therapy. Islet infusions will occur at the hospital and will be given intravenously. Participants will be eligible to receive second and third islet infusions if previous infusions fail and they continue to meet the eligibility criteria. After each infusion, study visits will occur on Days 1, 3, 7, 14, 21, 28, and 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 |
|---|---|---|
| Standard of Care | Active comparator | Drug: Heparin, Drug: CellCept® (Mycophenolate mofetil) OR Rapamune® (Sirolimus), Drug: Prograf® (Tacrolimus) OR Cyclosporine, Drug: Thymoglobulin® (Anti-thymocyte Globulin) - at first transplant, Drug: Simulect® (Basiliximab) - at 2nd or 3rd transplant, Drug: Klexane® (Enoxaparinsodium), Drug: Trombyl® or Albyl-E® (Acetylsalicylicacid- ASA), Drug: Enbrel® (Etanercept)18 participants randomized to protocol immunosuppression (Daclizumab OR Basiliximab; Tacrolimus OR Cyclosporine; Mycophenolate Mofetil OR Sirolimus; and heparin) without LMW-DS |
| LMW-DS | Experimental | Drug: Low Molecular Weight Sulfated Dextran (LMW-SD), Drug: CellCept® (Mycophenolate mofetil) OR Rapamune® (Sirolimus), Drug: Prograf® (Tacrolimus) OR Cyclosporine, Drug: Thymoglobulin® (Anti-thymocyte Globulin) - at first transplant, Drug: Simulect® (Basiliximab) - at 2nd or 3rd transplant, Drug: Klexane® (Enoxaparinsodium), Drug: Trombyl® or Albyl-E® (Acetylsalicylicacid- ASA), Drug: Enbrel® (Etanercept)18 participants randomized to protocol immunosuppression (Daclizumab OR Basiliximab; Tacrolimus OR Cyclosporine; Mycophenolate Mofetil OR Sirolimus; and heparin) and LMW-DS |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Mentally stable and able to comply with study procedures;
- Clinical history compatible with type 1 diabetes, with:
- Absent stimulated C-peptide (less than 0.3 ng/ml) 60 and 90 minutes post-mixed-meal tolerance test;
- Involvement of intensive diabetes management, defined as:
- At least one episode of severe hypoglycemia in the past 12 months, defined as an event with symptoms compatible with hypoglycemia in which the individual required assistance of another person and which was associated with either a blood glucose level less than 54 mg/dl or prompt recovery after an oral carbohydrate, intravenous glucose, or glucagon administration; and
Key exclusion criteria (35 listed)
- Known IgE mediated allergy to antibiotics used in the culture medium;
- Known hypersensitivity to dextran;
- Body mass index (BMI) greater than 30 kg/m^2;
- Insulin requirement of more than 1.0 IU/kg/day;
- HbA1c greater than 10%;
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 Dextran (LMW-SD)Inhibitor of IBMIR | Drug | LMW-DS |
| HeparinAnticoagulation | Drug | Standard of Care |
| CellCept® (Mycophenolate mofetil) OR Rapamune® (Sirolimus)Cell proliferation inhibitor | Drug | LMW-DS, Standard of Care |
| Prograf® (Tacrolimus) OR CyclosporineCalcineurin inhibitor | Drug | LMW-DS, Standard of Care |
| Thymoglobulin® (Anti-thymocyte Globulin) - at first transplant | Drug | LMW-DS, Standard of Care |
| Simulect® (Basiliximab) - at 2nd or 3rd transplantMonoclonal IL-2 receptor blocker | Drug | LMW-DS, Standard of Care |
| Klexane® (Enoxaparinsodium)Anticoagulation Prophylaxis | Drug | LMW-DS, Standard of Care |
| Trombyl® or Albyl-E® (Acetylsalicylicacid- ASA)Anticoagulation Prophylaxis | Drug | LMW-DS, Standard of Care |
| Enbrel® (Etanercept)Anti-Inflammatory Therapy | Drug | LMW-DS, Standard of Care |
Primary outcome
Level of stimulated c-peptide at 90-minute derived from the mixed-meal tolerance test (MMTT)
Time frame: At 70 to 80 days after first islet transfusion
19 secondary outcomes
Number of participants who achieve and maintain a 7.0% HbA1c level
Time frame: Throughout Study
Number of severe hypoglycemic events
Time frame: Throughout study
Percent reduction in insulin requirements
Time frame: At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion
Ryan hypoglycemia severity score ( HYPO) score
Time frame: : At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion
Proportion of participants with full graft function
Time frame: At 70 to 80 days after first islet transfusion and after the final islet infusion
C-peptide to glucose creatinine ratio
Time frame: At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion
Proportion of participants receiving a second islet infusion and proportion of participants receiving a third islet transfusion
Time frame: At 70 to 80 days after first islet transfusion and after the final islet infusion
Incidence and severity of adverse events related to islet infusion procedure
Time frame: At 70 to 80 days and 350 to 379 days after the first islet transfusion
Incidence of worsening retinopathy
Time frame: At 350 to 379 days after the first islet transfusion
HbA1c level
Time frame: At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion
Mean amplitude of glycemic excursions (MAGE)
Time frame: At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion
Glycemic lability index (LI)
Time frame: At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion
Clarke hypoglycemia awareness score
Time frame: At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion
Basal (fasting) and 90-minute glucose and c-peptide derived from MMTT
Time frame: : At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion
Beta-score
Time frame: At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion
Acute insulin response to glucose, insulin sensitivity, and disposition index derived from the insulin-modified frequently-sampled intravenous glucose tolerance (FSIGT) test,
Time frame: At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion
Glucose variability and hypoglycemic duration derived from continuous glucose monitoring system(CGMS)
Time frame: At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion
Incidence of a change in the immunosuppression drug regimen
Time frame: At 70 to 80 days and 350 to 379 days after the first islet transfusion
Incidence of immune sensitization defined by detecting anti-HLA antibodies not present prior to transplantation
Time frame: At 70 to 80 days and 350 to 379 days after the first islet transfusion
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 28 Sep 2021.
- Results publication: PubMed 30211831von Zur-Muhlen B, Lundgren T, Bayman L, Berne C, Bridges N, Eggerman T, Foss A, Goldstein J, Jenssen T, Jorns C, Morrison Y, Ryden M, Schwieger T, Tufveson G, Nilsson B, Korsgren O. Open Randomized Multicenter Study to Evaluate Safety and Efficacy of Low Molecular Weight Sulfated Dextran in Islet Transplantation. Transplantation. 2019 Mar;103(3):630-637. doi: 10.1097/TP.0000000000002425.
- National Institute of Allergy and Infectious Diseases (NIAID)Link provided by the sponsor.
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Link provided by the sponsor.
- Clinical Islet Transplantation Consortium websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. The plan is to share data upon completion of the study in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
Related trials for Diabetes Mellitus, Type I
RecruitingPhase 1
Pharmacokinetics, Safety, and Immunogenicity Comparison of Bmab1700 and Opdivo® as Adjuvant Monotherapy in Participants With Melanoma
Melanoma
Active, not recruitingPhase 2
A Study of Botensilimab and Balstilimab for the Treatment of Colorectal Cancer
Metastatic Colorectal Cancer
Not yet recruiting
Inter-Arm Differences in Continuous Glucose Monitor Readings in Adults With Diabetes
Continuous Glucose Monitoring, Type 1 Diabetes
RecruitingObservational study
Estimated Risk of Preeclampsia in the First Trimester and Its Association With Subclinical Atherosclerosis and Cardiovascular Risk in Women With Type 1 Diabetes
Type 1 Diabetes, Preeclampsia
Not yet recruiting
A Novel Miniature Equine-Assisted Diabetes Education Program for Youth: Evaluating the Diabetes Equine Empowerment Program (DEEP).
Diabetes (Insulin-requiring, Type 1 or Type 2), Pediatric Diabetes
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
Uppsala University Hospital
Torbjörn Lundgren, MD study chair
Karolinska University Hospital
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Low Molecular Weight Sulfated Dextran (LMW-SD), Heparin and CellCept® (Mycophenolate mofetil) OR Rapamune® (Sirolimus) in people with Diabetes Mellitus, Type I, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in 2 countries.
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 12 inclusion and 35 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 28 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Sweden, Norway. 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?
Level of stimulated c-peptide at 90-minute derived from the mixed-meal tolerance test (MMTT) (time frame: At 70 to 80 days after first islet transfusion). 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 NCT00789308, 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 28 Sep 2021.