Type 1 Diabetes MellitusPhase 2LEEPNCT00468403
LEA29Y (Belatacept) Emory Edmonton Protocol
A Phase 2 study testing Allogeneic Pancreatic Islet Cells, Belatacept and Basiliximab in people with Type 1 Diabetes Mellitus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 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 determine the safety and effectiveness of islet transplantation using a steroid-free, calcineurin-inhibitor-free belatacept based… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- Allogeneic Pancreatic Islet Cells, Belatacept and Basiliximab
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Oct 2008to Apr 2013
- 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 a 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
- Involvement of intensive diabetes management, defined as:
- Self-monitoring of glucose no less than a mean of three times each day averaged over each week
- Three or more insulin injections each day or insulin pump therapy
Show all 9Show fewer
- Under the care of an endocrinologist, diabetologist, or diabetes specialist with at least three clinical evaluations during the past 12 months prior to study enrollment
- At least one episode of severe hypoglycemia, defined as an event with one of the following symptoms: memory loss; confusion; uncontrollable behavior; irrational behavior; unusual difficulty in awakening; suspected seizure; seizure; loss of consciousness; or visual symptoms, in which the participant was unable to treat him/herself and which was associated with either a blood glucose level less than 54 mg/dL or prompt recovery after oral carbohydrate, intravenous glucose, or glucagons in the 12 months prior to study enrollment
- Reduced awareness of hypoglycemia. More information about this criterion is in the protocol.
Who cannot join
- Body mass index (BMI) greater than 30 kg/m^2 or weight less than or equal to 50 kg (110 lbs)
- Insulin requirement of more than 1.0 IU/kg/day or less than 15 U/day
- HbA1c greater than 10%
- Untreated proliferative diabetic retinopathy
- Systolic blood pressure higher than 160 mmHg or diastolic blood pressure higher than 100 mmHg
- Measured glomerular filtration rate using iohexol of less than 80 mL/min/1.73m^2.
Show all 41Show fewer
- Presence or history of macroalbuminuria (greater than 300 mg/g creatinine)
- Presence or history of panel-reactive anti-Histocompatibility Antigen (HLA) antibody levels greater than background by flow cytometry. More information about this criterion is in the protocol.
- Pregnant, breastfeeding, or unwilling to use effective contraception throughout the study and 4 months after study completion
- All women more than 35 years and women of any age who have first degree relatives with a history of breast carcinoma or who have other risk factors of breast carcinoma. More information about this criterion is in the study protocol.
- Active infection, including hepatitis B, hepatitis C, human immunodeficiency virus (HIV). Presence or history of tuberculosis. More information about these criteria is in the protocol.
- Negative for Epstein-Barr virus (EBV) by anti-viral capsid antigen (VCA) IgG (EBV VCA-IgG) determination
- Invasive aspergillus, histoplasmosis, or coccidioidomycosis infection in the past year
- History of malignancy except for 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
- History of Factor V deficiency
- Any coagulopathy or medical condition requiring long-term anticoagulant therapy after transplantation or individuals with an international normalized ratio (INR) greater than 1.5.
- Severe coexisting cardiac disease, defined as:
- Heart attack within the last 6 months
- Evidence of ischemia on functional heart exam within the year prior to study entry
- Left ventricular ejection fraction less than 30%
- Persistent elevation of liver function tests at study entry
- Symptomatic cholecystolithiasis
- Acute or chronic pancreatitis
- Symptomatic peptic ulcer disease
- Severe unremitting diarrhea, vomiting, or other gastrointestinal disorders that could interfere with the ability to absorb oral medications
- Hyperlipidemia despite medical therapy, defined as fasting LDL cholesterol greater than 130 mg/dL and/or fasting triglycerides greater than 200 mg/dL
- Currently receiving treatment for a medical condition that requires chronic use of systemic steroids except for the use of 5 mg or less of prednisone daily, or an equivalent dose of hydrocortisone, for physiological replacement only
- Treatment with any antidiabetic medication other than insulin within the past 4 weeks
- Previous receipt of belatacept
- Use of any investigational agents within the past 4 weeks
- Received a live attenuated vaccine(s) within the past 2 months
- Any medical condition that, in the opinion of the investigator, might interfere with safe participation in the trial
- Treatment with any immunosuppressive regimen at the time of enrollment.
- A previous islet transplant.
- A previous pancreas transplant, unless the graft failed within the first week due to thrombosis, followed by pancreatectomy and the transplant occurred more than 6 months prior to enrollment.
- Known hypersensitivity to mycophenolate mofetil or any of its components
- Imprisonment or involuntary incarceration for treatment of either a psychiatric or physical illness
- Rare hereditary deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) such as Lesch-Nyhan and Kelly-Seegmiller syndrome
- Dietary restriction of phenylalanine
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: Islet Transplantation in Type I Diabetes With LEA29Y (Belatacept) Maintenance Therapy (CIT-04)
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 determine the safety and effectiveness of islet transplantation using a steroid-free, calcineurin-inhibitor-free belatacept based immunosuppressive medication, for treating type 1 diabetes in individuals experiencing hypoglycemia unawareness and severe hypoglycemic episodes.
Read the detailed description
Type 1 diabetes 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 type 1 diabetes; 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. Some individuals with type 1 diabetes 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, transplantation of pancreatic islets is a possible treatment option. Unfortunately, insulin independence among islet transplant recipients tends to decline over time. New strategies aimed at promoting engraftment of transplanted islets are needed to improve the clinical outcomes associated with this procedure. The purpose of this study is determine the safety and efficacy of islet transplantation, when combined with an immunosuppressive medication regimen containing belatacept, for treating type 1 diabetes in individuals experiencing hypoglycemia unawareness and severe hypoglycemic episodes. This study will also seek to improve the understanding of determinants of success and failure of islet transplants for type 1 diabetes.
Eligible participants will be randomly assigned to this study or a site-specific Phase 3 islet transplantation study (CIT-07). Participants in this study will receive up to three separate islet transplants and a regimen of immunosuppressive medications consisting of belatacept, basiliximab (an IL-2 monoclonal antibody receptor blocker), and mycophenolate mofetil. Participants will begin receiving all three drugs on the day of the first islet transplant. Belatacept will also be administered again on Days 4, 14, 28, 56, and 84 post-transplant and then every 4 weeks for the duration of the study.
If the participant receives daclizumab, it will also be given again on Days 14, 28, 42, and 56 post-transplant; if the participant receives basiliximab, it will also be given again on Day 4 post-transplant. Mycophenolate mofetil will also be given for the duration of the study.
Transplantations will involve an inpatient hospital stay and intraportal infusion of islet cells. Participants who do not achieve or maintain insulin independence by Day 75 post-transplant will be considered for a second islet transplant. Participants who remain dependent on insulin for longer than 1 month after the second transplant and who show partial graft function will be considered for a third islet transplant. Participants who do not meet the criteria for a subsequent transplant and do not have a functioning graft will enter a reduced follow-up period.
There will be up to 25 study visits following each transplant. A physical exam, review of adverse events, and blood collection will occur at most visits. A chest x-ray, abdominal ultrasound, electrocardiogram, quality of life questionnaires, urine collection, and more extensive blood testing will occur at some visits. Participants will also test their own blood glucose levels at least five times per day throughout the study. A 24-month follow-up period will take place after the participant's last transplant.
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- Allogeneic Pancreatic Islet Cells, Belatacept, Basiliximab, Mycophenolate Mofetil, Tacrolimus
- Keywords
- Insulin dependence, Hypoglycemia, Hypoglycemia unawareness
- Medical subject headings
- Diabetes Mellitus, Type 1, Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogeneic Pancreatic Islet CellsBiological
Transplant of islet cells from a healthy pancreas. A dose of at least 5,000 Islet Equivalents (IEQ)/kg recipient body weight (BW) infused intraportally for the first transplant, and at least 4,000 IEQ/kg recipient BW infused intraportally for subsequent transplants.
BelataceptBiological
Also called NUJOLIX
Belatacept is an inhibitor of the 2 signals that stimulate T-cells. Subjects will receive NULOJIX® (belatacept)10mg/kg through a peripheral vein on Day 0 and post-operative days 4, 14, 28, 56, 84. After Day 84 subjects will receive belatacept at a maintenance dose of 5 mg/kg every 4 weeks for the duration of study follow-up (2 years after the final islet transplant). Infusion doses will be based upon the subject's actual body weight at study Day 0 and will not be modified during the course of the study unless there is a change in body weight plus or minus 10% of Day 0 body weight.
BasiliximabBiological
Also called Simulect
Immunosuppressive medication for prophylaxis of acute transplant rejection. Two Intravenous (IV) doses of basiliximab, a monoclonal antibody Interleukin 2 (IL-2) receptor blocker, will be given with the first and second (if necessary) transplants. The first dose will be 20 mg and will be given within two hours prior to islet transplant on the day of islet transplantation. The second 20 mg dose will be given on Day 4 after the transplant.If a third islet transplant is deemed necessary and performed more than 70 days after the second transplant, both doses of basiliximab will be repeated. No additional doses of basiliximab will be given with a third transplant that is performed between 30 and 70 days after the second transplant.
Also called Cellcept
Maintenance immunosuppressive therapy. Subjects will receive mycophenolate mofetil starting immediately pre-transplant on Day 0 at a dose of 1g orally twice a day for the duration of study follow-up (2 years after the final islet transplant).
TacrolimusDrug
Also called Prograf
Tacrolimus may be used only as a supplement to maintenance mycophenolate mofetil (MMF) in those cases where the trough level is below the therapeutic range. Tacrolimus will be administered orally twice a day to maintain trough levels of 3-5 ng/mL. Generic equivalents of Prograf® will not be permitted.
Intraportal infusion of islet cellsProcedure or surgery
The infusion of allogeneic pancreatic islet cells (islet transplant[s]) will occur intraportally.
| Study group | Role | What they receive |
|---|---|---|
| Allogeneic Pancreatic Islet Cells | Experimental | Participants will receive up to three islet transplantations and continuous immunosuppressive therapy including belatacept Receives: Biological: Allogeneic Pancreatic Islet Cells; Biological: Belatacept; Biological: Basiliximab; Drug: Mycophenolate Mofetil; Drug: Tacrolimus; Procedure: Intraportal infusion of islet cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of subjects with insulin independence
Measured: 75 days after first islet transplant
Secondary outcomes (29)
Proportion of subjects with an HbA1c <7.0% AND free of severe hypoglycemic events
Measured: from Day 28 to Day 365, inclusive, after the first islet transplant
Proportion of subjects with an HbA1c <7.0% AND free of severe hypoglycemic events
Measured: from Day 28 to Day 365, inclusive, after the final islet transplant
Percent reduction in insulin requirements, HbA1c, Mean amplitude of glycemic excursions (MAGE), Glycemic lability index (LI), Ryan hypoglycemia severity (HYPO) score
Measured: 75 Days after first and final islet transplant
Basal (fasting) and 90-min glucose and C-peptide derived from the mixed-meal tolerance test (MMTT), beta-score, C-peptide: glucose-creatinine ration, acute insulin response to glucose
Measured: 75 Days after first and final islet transplant
Insulin sensitivity and disposition index derived from the insulin-modified frequently-sampled intravenous glucose tolerance test (FSIGT) test
Measured: 75 days after first and final islet transplant
Glucose variability and hypoglycemia duration, derived from the continuous glucose monitoring system (CGMS), quality of life (QOL) measures
Measured: 75 days after first and final islet transplant
Percent reduction in insulin requirements, HbA1c, Mean amplitude of glycemic excursions (MAGE), Glycemic lability index (LI), Clarke Score, Ryan hypoglycemia severity (HYPO) score
Measured: 365 days after first and final islet transplant
Basal (fasting) and 90-min glucose and C-peptide derived from the mixed-meal tolerance test (MMTT), beta-score, C-peptide: glucose-creatinine ratio
Measured: 365 days after first and final islet transplant
Insulin sensitivity and disposition index derived from the insulin-modified frequently-sampled intravenous glucose tolerance test (FSIGT) test
Measured: 365 days after first and final islet transplant
Glucose variability and hypoglycemia duration, derived from the continuous glucose monitoring system (CGMS), quality of life (QOL) measures
Measured: 365 days after first and final islet transplant
Proportion of participants receiving a second or third islet transplant
Measured: 365 days after first and final islet transplant
Rate of favorable outcome at each center preparing islets (rate of subjects with an HbA1c < 7.0% and free of severe hypoglycemic events)
Measured: 365 days after first and final islet transplant
Incidence and severity of adverse events related to the islet transplant procedure
Measured: 75 days following each transplant and 365 days following the first and final islet transplant
Incidence and severity of adverse events related to immunosuppression therapy
Measured: 75 days following each transplant and 365 days following the first and final islet transplant
Incidence of change in the immunosuppression drug regimen
Measured: 75 days following each transplant and 365 days following the first and final islet transplant
Incidence of immune sensitization defined by presence of Histocompatibility Antigen (HLA) antibodies absent prior to transplantation
Measured: 75 days following each transplant and 365 days following the first and final islet transplant
Incidence of worsening retinopathy
Measured: 365 days following the first islet transplant
Percent reduction in insulin requirements, HbA1c, Mean amplitude of glycemic excursions (MAGE), Glycemic lability index (LI), Clarke Score, Ryan hypoglycemia severity (HYPO) score
Measured: From 75 days to 365 days after final islet transplant
Basal (fasting) and 90-min glucose and C-peptide derived from the mixed-meal tolerance test (MMTT), beta-score, C-peptide: glucose-creatinine ratio
Measured: From 75 days to 365 days after final islet transplant
Insulin sensitivity and disposition index derived from the insulin-modified frequently-sampled intravenous glucose tolerance test (FSIGT) test
Measured: From 75 days to 365 days after final islet transplant
Glucose variability and hypoglycemia duration, derived from the continuous glucose monitoring system (CGMS), quality of life (QOL) measures
Measured: From 75 days to 365 days after final islet transplant
Proportion of participants receiving a second or third islet transplant
Measured: From 75 days to 365 days after final islet transplant
Rate of favorable outcome at each center preparing islets (rate of subjects with an HbA1c < 7.0% and free of severe hypoglycemic events)
Measured: From 75 days to 365 days after final islet transplant
Percent reduction in insulin requirements, number of severe hypoglycemic events from 28 days to 2 years, HbA1c, Clarke Score
Measured: Two years after final islet transplant
Basal (fasting) and 90-min glucose and C-peptide derived from the mixed-meal tolerance test (MMTT), beta-score, C-peptide
Measured: Two years after final islet transplant
Glucose variability and hypoglycemia duration, derived from the continuous glucose monitoring system (CGMS), quality of life (QOL) measures
Measured: Two years after final islet transplant
Safety associated with conventional immunosuppression
Measured: Two years after final islet transplant
Renal function as measured by serum creatinine, glomerular filtration rate (GFR) and other relevant laboratory parameters
Measured: Two years after final islet transplant
Lipid profiles (triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol)
Measured: Two years after final islet transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2007 (estimated)
- Study startOct 2008
- Primary completionApr 2012
- Study completionApr 2013
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 Type 1 Diabetes MellitusStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Clinical Islet Transplantation Consortium
- Responsible party
- Sponsor
- Investigators
- A.M. James Shapiro, MD, PhD, Study chair, Clinical Islet Transplant Program, University of AlbertaNicole Turgeon, MD, Study chair, Clinical Islet Transplant Program, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00468403
- Sponsor's protocol ID
- DAIT CIT-04
- Acronym
- LEEP
- Status last verified
- Mar 2016
- First submitted
- 1 May 2007
- Last updated
- 7 Apr 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Gala-Lopez B, Kin T, O'Gorman D, Pepper AR, Senior P, Humar A, Shapiro AM. Microbial contamination of clinical islet transplant preparations is associated with very low risk of infection. Diabetes Technol Ther. 2013 Apr;15(4):323-7. doi: 10.1089/dia.2012.0297. Epub 2013 Feb 25.
PubMed 23438305
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Islet Transplantation in Type I Diabetes With LEA29Y (Belatacept) Maintenance Therapy (CIT-04)
- ClinicalTrials.gov ID
- NCT00468403
- Acronym / sponsor ID
- LEEP / DAIT CIT-04
- Conditions
- Type 1 Diabetes Mellitus
- Keywords
- Insulin dependence, Hypoglycemia, Hypoglycemia unawareness
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Clinical Islet Transplantation Consortium
- Study start
- Oct 2008
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 2 May 2007 (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 determine the safety and effectiveness of islet transplantation using a steroid-free, calcineurin-inhibitor-free belatacept based immunosuppressive medication, for treating type 1 diabetes in individuals experiencing hypoglycemia unawareness and severe hypoglycemic episodes.
Detailed description
Type 1 diabetes 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 type 1 diabetes; 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. Some individuals with type 1 diabetes 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, transplantation of pancreatic islets is a possible treatment option. Unfortunately, insulin independence among islet transplant recipients tends to decline over time. New strategies aimed at promoting engraftment of transplanted islets are needed to improve the clinical outcomes associated with this procedure. The purpose of this study is determine the safety and efficacy of islet transplantation, when combined with an immunosuppressive medication regimen containing belatacept, for treating type 1 diabetes in individuals experiencing hypoglycemia unawareness and severe hypoglycemic episodes. This study will also seek to improve the understanding of determinants of success and failure of islet transplants for type 1 diabetes.
Eligible participants will be randomly assigned to this study or a site-specific Phase 3 islet transplantation study (CIT-07). Participants in this study will receive up to three separate islet transplants and a regimen of immunosuppressive medications consisting of belatacept, basiliximab (an IL-2 monoclonal antibody receptor blocker), and mycophenolate mofetil. Participants will begin receiving all three drugs on the day of the first islet transplant. Belatacept will also be administered again on Days 4, 14, 28, 56, and 84 post-transplant and then every 4 weeks for the duration of the study.
If the participant receives daclizumab, it will also be given again on Days 14, 28, 42, and 56 post-transplant; if the participant receives basiliximab, it will also be given again on Day 4 post-transplant. Mycophenolate mofetil will also be given for the duration of the study.
Transplantations will involve an inpatient hospital stay and intraportal infusion of islet cells. Participants who do not achieve or maintain insulin independence by Day 75 post-transplant will be considered for a second islet transplant. Participants who remain dependent on insulin for longer than 1 month after the second transplant and who show partial graft function will be considered for a third islet transplant. Participants who do not meet the criteria for a subsequent transplant and do not have a functioning graft will enter a reduced follow-up period.
There will be up to 25 study visits following each transplant. A physical exam, review of adverse events, and blood collection will occur at most visits. A chest x-ray, abdominal ultrasound, electrocardiogram, quality of life questionnaires, urine collection, and more extensive blood testing will occur at some visits. Participants will also test their own blood glucose levels at least five times per day throughout the study. A 24-month follow-up period will take place after the participant's last transplant.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Allogeneic Pancreatic Islet Cells | Experimental | Biological: Allogeneic Pancreatic Islet Cells, Biological: Belatacept, Biological: Basiliximab, Drug: Mycophenolate Mofetil, Drug: Tacrolimus, Procedure: Intraportal infusion of islet cellsParticipants will receive up to three islet transplantations and continuous immunosuppressive therapy including belatacept |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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 a 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
- Involvement of intensive diabetes management, defined as:
- At least one episode of severe hypoglycemia, defined as an event with one of the following symptoms: memory loss; confusion; uncontrollable behavior; irrational behavior; unusual difficulty in awakening; suspected seizure; seizure; loss of consciousness; or visual symptoms, in which the participant was unable to treat him/herself and which was associated with either a blood glucose level less than 54 mg/dL or prompt recovery after oral carbohydrate, intravenous glucose, or glucagons in the 12 months prior to study enrollment
Key exclusion criteria (41 listed)
- Body mass index (BMI) greater than 30 kg/m^2 or weight less than or equal to 50 kg (110 lbs)
- Insulin requirement of more than 1.0 IU/kg/day or less than 15 U/day
- HbA1c greater than 10%
- Untreated proliferative diabetic retinopathy
- Systolic blood pressure higher than 160 mmHg or diastolic blood pressure higher than 100 mmHg
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 |
|---|---|---|
| Allogeneic Pancreatic Islet CellsTransplant of islet cells from a healthy pancreas. A dose of at least 5,000 Islet Equivalents (IEQ)/kg recipient body weight (BW) infused intraportally for the first transplant, and at least 4,000 IEQ/kg recipient BW infused intraportally for subsequent transplants. | Biological | Allogeneic Pancreatic Islet Cells |
| BelataceptAlso: NUJOLIXBelatacept is an inhibitor of the 2 signals that stimulate T-cells. Subjects will receive NULOJIX® (belatacept)10mg/kg through a peripheral vein on Day 0 and post-operative days 4, 14, 28, 56, 84. After Day 84 subjects will receive belatacept at a maintenance dose of 5 mg/kg every 4 weeks for the duration of study follow-up (2 years after the final islet transplant). Infusion doses will be based upon the subject's actual body weight at study Day 0 and will not be modified during the course of the study unless there is a change in body weight plus or minus 10% of Day 0 body weight. | Biological | Allogeneic Pancreatic Islet Cells |
| BasiliximabAlso: SimulectImmunosuppressive medication for prophylaxis of acute transplant rejection. Two Intravenous (IV) doses of basiliximab, a monoclonal antibody Interleukin 2 (IL-2) receptor blocker, will be given with the first and second (if necessary) transplants. The first dose will be 20 mg and will be given within two hours prior to islet transplant on the day of islet transplantation. The second 20 mg dose will be given on Day 4 after the transplant.If a third islet transplant is deemed necessary and performed more than 70 days after the second transplant, both doses of basiliximab will be repeated. No additional doses of basiliximab will be given with a third transplant that is performed between 30 and 70 days after the second transplant. | Biological | Allogeneic Pancreatic Islet Cells |
| Mycophenolate MofetilAlso: CellceptMaintenance immunosuppressive therapy. Subjects will receive mycophenolate mofetil starting immediately pre-transplant on Day 0 at a dose of 1g orally twice a day for the duration of study follow-up (2 years after the final islet transplant). | Drug | Allogeneic Pancreatic Islet Cells |
| TacrolimusAlso: PrografTacrolimus may be used only as a supplement to maintenance mycophenolate mofetil (MMF) in those cases where the trough level is below the therapeutic range. Tacrolimus will be administered orally twice a day to maintain trough levels of 3-5 ng/mL. Generic equivalents of Prograf® will not be permitted. | Drug | Allogeneic Pancreatic Islet Cells |
| Intraportal infusion of islet cellsThe infusion of allogeneic pancreatic islet cells (islet transplant[s]) will occur intraportally. | Procedure or surgery | Allogeneic Pancreatic Islet Cells |
Primary outcome
Proportion of subjects with insulin independence
Time frame: 75 days after first islet transplant
29 secondary outcomes
Proportion of subjects with an HbA1c <7.0% AND free of severe hypoglycemic events
Time frame: from Day 28 to Day 365, inclusive, after the first islet transplant
Proportion of subjects with an HbA1c <7.0% AND free of severe hypoglycemic events
Time frame: from Day 28 to Day 365, inclusive, after the final islet transplant
Percent reduction in insulin requirements, HbA1c, Mean amplitude of glycemic excursions (MAGE), Glycemic lability index (LI), Ryan hypoglycemia severity (HYPO) score
Time frame: 75 Days after first and final islet transplant
Basal (fasting) and 90-min glucose and C-peptide derived from the mixed-meal tolerance test (MMTT), beta-score, C-peptide: glucose-creatinine ration, acute insulin response to glucose
Time frame: 75 Days after first and final islet transplant
Insulin sensitivity and disposition index derived from the insulin-modified frequently-sampled intravenous glucose tolerance test (FSIGT) test
Time frame: 75 days after first and final islet transplant
Glucose variability and hypoglycemia duration, derived from the continuous glucose monitoring system (CGMS), quality of life (QOL) measures
Time frame: 75 days after first and final islet transplant
Percent reduction in insulin requirements, HbA1c, Mean amplitude of glycemic excursions (MAGE), Glycemic lability index (LI), Clarke Score, Ryan hypoglycemia severity (HYPO) score
Time frame: 365 days after first and final islet transplant
Basal (fasting) and 90-min glucose and C-peptide derived from the mixed-meal tolerance test (MMTT), beta-score, C-peptide: glucose-creatinine ratio
Time frame: 365 days after first and final islet transplant
Insulin sensitivity and disposition index derived from the insulin-modified frequently-sampled intravenous glucose tolerance test (FSIGT) test
Time frame: 365 days after first and final islet transplant
Glucose variability and hypoglycemia duration, derived from the continuous glucose monitoring system (CGMS), quality of life (QOL) measures
Time frame: 365 days after first and final islet transplant
Proportion of participants receiving a second or third islet transplant
Time frame: 365 days after first and final islet transplant
Rate of favorable outcome at each center preparing islets (rate of subjects with an HbA1c < 7.0% and free of severe hypoglycemic events)
Time frame: 365 days after first and final islet transplant
Incidence and severity of adverse events related to the islet transplant procedure
Time frame: 75 days following each transplant and 365 days following the first and final islet transplant
Incidence and severity of adverse events related to immunosuppression therapy
Time frame: 75 days following each transplant and 365 days following the first and final islet transplant
Incidence of change in the immunosuppression drug regimen
Time frame: 75 days following each transplant and 365 days following the first and final islet transplant
Incidence of immune sensitization defined by presence of Histocompatibility Antigen (HLA) antibodies absent prior to transplantation
Time frame: 75 days following each transplant and 365 days following the first and final islet transplant
Incidence of worsening retinopathy
Time frame: 365 days following the first islet transplant
Percent reduction in insulin requirements, HbA1c, Mean amplitude of glycemic excursions (MAGE), Glycemic lability index (LI), Clarke Score, Ryan hypoglycemia severity (HYPO) score
Time frame: From 75 days to 365 days after final islet transplant
Basal (fasting) and 90-min glucose and C-peptide derived from the mixed-meal tolerance test (MMTT), beta-score, C-peptide: glucose-creatinine ratio
Time frame: From 75 days to 365 days after final islet transplant
Insulin sensitivity and disposition index derived from the insulin-modified frequently-sampled intravenous glucose tolerance test (FSIGT) test
Time frame: From 75 days to 365 days after final islet transplant
Glucose variability and hypoglycemia duration, derived from the continuous glucose monitoring system (CGMS), quality of life (QOL) measures
Time frame: From 75 days to 365 days after final islet transplant
Proportion of participants receiving a second or third islet transplant
Time frame: From 75 days to 365 days after final islet transplant
Rate of favorable outcome at each center preparing islets (rate of subjects with an HbA1c < 7.0% and free of severe hypoglycemic events)
Time frame: From 75 days to 365 days after final islet transplant
Percent reduction in insulin requirements, number of severe hypoglycemic events from 28 days to 2 years, HbA1c, Clarke Score
Time frame: Two years after final islet transplant
Basal (fasting) and 90-min glucose and C-peptide derived from the mixed-meal tolerance test (MMTT), beta-score, C-peptide
Time frame: Two years after final islet transplant
Glucose variability and hypoglycemia duration, derived from the continuous glucose monitoring system (CGMS), quality of life (QOL) measures
Time frame: Two years after final islet transplant
Safety associated with conventional immunosuppression
Time frame: Two years after final islet transplant
Renal function as measured by serum creatinine, glomerular filtration rate (GFR) and other relevant laboratory parameters
Time frame: Two years after final islet transplant
Lipid profiles (triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol)
Time frame: Two years after final islet transplant
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 7 Apr 2016.
- Derived from this study: PubMed 23438305Gala-Lopez B, Kin T, O'Gorman D, Pepper AR, Senior P, Humar A, Shapiro AM. Microbial contamination of clinical islet transplant preparations is associated with very low risk of infection. Diabetes Technol Ther. 2013 Apr;15(4):323-7. doi: 10.1089/dia.2012.0297. Epub 2013 Feb 25.
- Click here for the Clinical Islet Transplantation Consortium Web siteLink provided by the sponsor.
- National Institute of Allergy and Infectious DiseasesLink 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.
A.M. James Shapiro, MD, PhD study chair
Clinical Islet Transplant Program, University of Alberta
Nicole Turgeon, MD study chair
Clinical Islet Transplant Program, Emory University
2 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 Allogeneic Pancreatic Islet Cells, Belatacept and Basiliximab in people with Type 1 Diabetes Mellitus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 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 9 inclusion and 41 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 7 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Canada. 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?
Proportion of subjects with insulin independence (time frame: 75 days after first islet transplant). 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 NCT00468403, 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 7 Apr 2016.