Type 1 Diabetes MellitusPhase 3NCT00468117
Efficacy of Islet After Kidney Transplantation
A Phase 3 study testing Islet transplantation, Antithymocyte Globulin and Daclizumab or Basiliximab in people with Type 1 Diabetes Mellitus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 10 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 benefit of islet transplantation in type 1 diabetic (T1D) kidney transplant recipients. Read more about this study
- Who is it for?
- Ages 18 to 68 years
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- Islet transplantation, Antithymocyte Globulin and Daclizumab or Basiliximab
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 10 sitesin 2 countries
- Study dates
- Jan 2007to 5 Jul 2017
- Phase
- Phase 3
- 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 68 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 (defined as less than 0.3 ng/ml) 60 and 90 minutes post-mixed-meal tolerance test;
- Received kidney transplant for ESRD and are taking appropriate calcineurin inhibitor (CNI) based maintenance immunosuppressive therapy;
- Stable renal function as defined as creatinine of no more than one third greater than the average creatinine determination performed in the 3 previous months prior to islet transplantation, until rejection, obstruction or infection is ruled out;
- Intensive diabetes management followed by reduced awareness of hypoglycemia or an HbA1c ≥ 7.5%.
Who cannot join
- Body mass index (BMI) greater than 30 kg/m2 or weight more than 90 kg;
- Insulin requirement of >1.0 IU/kg/day or <15 U/day;
- Other (non-kidney) organ transplants except prior failed pancreatic graft where the graft failed within the first two weeks due to thrombosis, followed by pancreatectomy and the pancreas transplant occurred more than 6 months prior to enrollment;
- Untreated proliferative diabetic retinopathy;
- Systolic blood pressure higher than 160 mmHg or diastolic blood pressure higher than 100 mmHg;
- Calculated glomerular filtration rate of less than 40 ml/min/1.73meter-squared. More information about this criterion is in the protocol;
Show all 37Show fewer
- Proteinuria (albumin/creatinine ratio or ACr > 300 mg/g) of new onset since kidney transplantation;
- Either Class I or Class II panel-reactive anti-HLA antibodies > 50%; Participants with either Class I or Class II panel reactive anti-HLA antibodies of 50% or less will be excluded if any of the following are detected:
- Positive cross match;
- Islet donor-directed anti-HLA antibodies detected my Luminex Single Antigen/specificity bead assay, including weakly reactive antibodies that would not be detected by a flow cross-match; or
- Antibodies to the renal donor (i.e. presumed de novo).
- Pregnant, breastfeeding, or unwilling to use effective contraception throughout the study and 4 months after study completion;
- Active infection, including hepatitis B, hepatitis C, HIV, or tuberculosis. More information about this criterion is in the protocol.
- Negative for Epstein-Barr virus (EBV) by (VCA) IgG determination;
- Invasive aspergillus infection, histoplasmosis, and coccidioidomycosis infection one year prior to study enrollment;
- History of malignancy except for completely resected squamous or basal cell carcinoma of the skin;
- Known active alcohol or substance abuse;
- History of Factor V Leiden mutation;
- Any coagulopathy or medical condition requiring long-term anticoagulant therapy after transplantation or individuals with an INR greater than 1.5;
- Severe co-existing cardiac disease, characterized by any one of these conditions:
- Recent MI (within past 6 months);
- Evidence of ischemia on functional cardiac exam within the last year;
- Left ventricular ejection fraction < 30%; or
- Valvular disease requiring replacement with prosthetic valve.
- Persistent elevation of liver function tests at the time of study entry. Persistent serum glutamic-oxaloacetic transaminase (SGOT [AST]), serum glutamate pyruvate transaminase (SGPT [ALT],) alkaline phosphatase or total bilirubin, with values > 1.5 times normal upper limits will exclude a subject;
- Active infections (except mild skin and nail fungal infections);
- Acute or chronic pancreatitis;
- Active peptic ulcer disease, symptomatic gallstones, or portal hypertension;
- Treatment with any anti-diabetic medication other than insulin within the past 4 weeks;
- Use of any investigational agents within the past 4 weeks;
- Received live attenuated vaccine(s) within the past 2 months;
- Any medical condition that, in the opinion of the investigator, will interfere with safe participation in the trial;
- Male participants with elevation of prostate specific antigen (PSA) of more than 4 unless cancer has been excluded;
- Any condition other than T1D as the primary cause of end stage renal disease (ESRD) in the native kidney;
- Positive screen for BK virus by polymerase chain reaction (PCR) determination at time of screening;
- A previous islet transplant;
- A kidney transplant recipient with T1D who has an HbA1c < 7.5% and no history of severe hypoglycemia.
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
United States9 sites
Emory Universtiy
Atlanta, Georgia, 30322
Massachusetts General Hospital
Boston, Massachusetts, 02114
Northwestern University
Chicago, Illinois, 60208
University of Illinois at Chicago
Chicago, Illinois, 60607
University of Wisconsin
Madison, Wisconsin, 53792
University of Miami
Miami, Florida, 33124
University of Minnesota
Minneapolis, Minnesota, 55455
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of California, San Francisco
San Francisco, California, 94143
About this study
Official title: Islet Transplantation in Type 1 Diabetic Kidney Allograft Recipients: Efficacy of Islet After Kidney Transplantation (CIT-06)
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 benefit of islet transplantation in type 1 diabetic (T1D) kidney transplant recipients.
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 and thus kidney transplant. 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, pancreas or pancreatic islet transplantation are possible treatment options. The purpose of this study is to assess the benefit of islet transplantation in type 1 diabetic kidney transplant recipients.
Participants in this study will be type I diabetics who have received a kidney transplant for ESRD.. If subjects have not received ITT in the 12 months prior to enrollment, they must undergo a period of standardized diabetes care by an experienced diabetologist at the transplant center using the current ADA's standards of medical care in diabetes. Throughout the study, all participants will remain on the immunosuppressive therapy intended for their kidney. Participants will receive up to three separate islet transplants and a regimen of immunosuppressive medications consisting of antithymocyte globulin (ATG) and etanercept. They will begin receiving ATG 2 days prior to transplant and will continue to receive ATG until Day 2 post-transplant. Etanercept will be given on the day of transplant and on Days 3, 7, and 10 post-transplant.
Transplantations will involve an inpatient hospital stay and infusion of islets into a branch of the portal vein. Participants who do not achieve or maintain insulin independence by Day 30 post-transplant will be considered for a second islet transplant. Participants who remain dependent on insulin for longer than 30 days after the second transplant and who show partial graft function will be considered for a third islet transplant. Daclizumab will be used in place of ATG for the second and third transplants, if they are necessary. Participants who do not meet the criteria for a subsequent transplant will enter a reduced follow-up period.
There will be approximately 15 study visits. 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, and urine collection will occur at some visits. Participants will also test their own blood glucose levels throughout the study. A 36-month follow-up period will take place after the participant's last transplant, consisting of 8 additional visits.
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- Islet transplantation, Antithymocyte Globulin, Daclizumab or Basiliximab, Etanercept, Allogenic human purified pancreatic islets
- Keywords
- Hypoglycemia, Kidney Transplant, Insulin independence, Islet Transplantation, Intensive Insulin Therapy
- 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.
Islet transplantationProcedure or surgery
Antithymocyte GlobulinBiological
Also called ATG
Participants will begin receiving ATG 2 days prior to the initial islet transplant and will continue to receive ATG until Day 2 post-transplant.
Daclizumab or BasiliximabBiological
Daclizumab or Basiliximab will be used for subsequent transplants.
EtanerceptBiological
Etanercept will be given on the day of transplant and on Days 3, 7, and 10 post-transplant.
Allogenic human purified pancreatic isletsBiological
200 ml suspension of allogenic human purified islets
| Study group | Role | What they receive |
|---|---|---|
| Islet transplantation | Experimental | Up to three separate islet transplants will occur and a regimen of immunosuppressive medications consisting of antithymocyte globulin (ATG) and etanercept throughout study. Receives: Procedure: Islet transplantation; Biological: Antithymocyte Globulin; Biological: Daclizumab or Basiliximab; Biological: Etanercept; Biological: Allogenic human purified pancreatic islets |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients w/HbA1c </= to 6.5% and an absence of severe hypoglycemic events or a reduction in HbA1c of at least 1 point and an absence of severe hypoglycemic events
Measured: At 1 year after first islet infusion
Secondary outcomes (1)
Reduction in insulin requirements, HbA1c, MAGE, LI, HYPO score, fasting glucose, beta score, serum creatinine, c-peptide levels, MMTT, Clarke Survey, FSIGT, CGMS, number of hypoglycemic events, renal impact, cardiovascular impact, and quality of life
Measured: At 1 year after first islet infusion and/or 1 year after final islet infusion
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 startJan 2007
- Primary completionJul 2015
- Study completion5 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- James F. Markmann, MD, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00468117
- Sponsor's protocol ID
- DAIT CIT-06
- Status last verified
- Oct 2017
- First submitted
- 1 May 2007
- Last updated
- 20 Oct 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Islet Transplantation in Type 1 Diabetic Kidney Allograft Recipients: Efficacy of Islet After Kidney Transplantation (CIT-06)
- ClinicalTrials.gov ID
- NCT00468117
- Acronym / sponsor ID
- DAIT CIT-06
- Conditions
- Type 1 Diabetes Mellitus
- Keywords
- Hypoglycemia, Kidney Transplant, Insulin independence, Islet Transplantation, Intensive Insulin Therapy
- Phase
- Phase 3
- 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)
- Study start
- Jan 2007
- Primary completion
- Jul 2015 (actual)
- Study completion
- 5 Jul 2017 (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 assess the benefit of islet transplantation in type 1 diabetic (T1D) kidney transplant recipients.
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 and thus kidney transplant. 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, pancreas or pancreatic islet transplantation are possible treatment options. The purpose of this study is to assess the benefit of islet transplantation in type 1 diabetic kidney transplant recipients.
Participants in this study will be type I diabetics who have received a kidney transplant for ESRD.. If subjects have not received ITT in the 12 months prior to enrollment, they must undergo a period of standardized diabetes care by an experienced diabetologist at the transplant center using the current ADA's standards of medical care in diabetes. Throughout the study, all participants will remain on the immunosuppressive therapy intended for their kidney. Participants will receive up to three separate islet transplants and a regimen of immunosuppressive medications consisting of antithymocyte globulin (ATG) and etanercept. They will begin receiving ATG 2 days prior to transplant and will continue to receive ATG until Day 2 post-transplant. Etanercept will be given on the day of transplant and on Days 3, 7, and 10 post-transplant.
Transplantations will involve an inpatient hospital stay and infusion of islets into a branch of the portal vein. Participants who do not achieve or maintain insulin independence by Day 30 post-transplant will be considered for a second islet transplant. Participants who remain dependent on insulin for longer than 30 days after the second transplant and who show partial graft function will be considered for a third islet transplant. Daclizumab will be used in place of ATG for the second and third transplants, if they are necessary. Participants who do not meet the criteria for a subsequent transplant will enter a reduced follow-up period.
There will be approximately 15 study visits. 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, and urine collection will occur at some visits. Participants will also test their own blood glucose levels throughout the study. A 36-month follow-up period will take place after the participant's last transplant, consisting of 8 additional visits.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Islet transplantation | Experimental | Procedure: Islet transplantation, Biological: Antithymocyte Globulin, Biological: Daclizumab or Basiliximab, Biological: Etanercept, Biological: Allogenic human purified pancreatic isletsUp to three separate islet transplants will occur and a regimen of immunosuppressive medications consisting of antithymocyte globulin (ATG) and etanercept throughout study. |
Who may qualify
- Ages
- 18 to 68 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 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 (defined as less than 0.3 ng/ml) 60 and 90 minutes post-mixed-meal tolerance test;
- Received kidney transplant for ESRD and are taking appropriate calcineurin inhibitor (CNI) based maintenance immunosuppressive therapy;
- Stable renal function as defined as creatinine of no more than one third greater than the average creatinine determination performed in the 3 previous months prior to islet transplantation, until rejection, obstruction or infection is ruled out;
Key exclusion criteria (37 listed)
- Body mass index (BMI) greater than 30 kg/m2 or weight more than 90 kg;
- Insulin requirement of >1.0 IU/kg/day or <15 U/day;
- Other (non-kidney) organ transplants except prior failed pancreatic graft where the graft failed within the first two weeks due to thrombosis, followed by pancreatectomy and the pancreas transplant occurred more than 6 months prior to enrollment;
- 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 |
|---|---|---|
| Islet transplantation | Procedure or surgery | Islet transplantation |
| Antithymocyte GlobulinAlso: ATGParticipants will begin receiving ATG 2 days prior to the initial islet transplant and will continue to receive ATG until Day 2 post-transplant. | Biological | Islet transplantation |
| Daclizumab or BasiliximabDaclizumab or Basiliximab will be used for subsequent transplants. | Biological | Islet transplantation |
| EtanerceptEtanercept will be given on the day of transplant and on Days 3, 7, and 10 post-transplant. | Biological | Islet transplantation |
| Allogenic human purified pancreatic islets200 ml suspension of allogenic human purified islets | Biological | Islet transplantation |
Primary outcome
Proportion of patients w/HbA1c </= to 6.5% and an absence of severe hypoglycemic events or a reduction in HbA1c of at least 1 point and an absence of severe hypoglycemic events
Time frame: At 1 year after first islet infusion
1 secondary outcome
Reduction in insulin requirements, HbA1c, MAGE, LI, HYPO score, fasting glucose, beta score, serum creatinine, c-peptide levels, MMTT, Clarke Survey, FSIGT, CGMS, number of hypoglycemic events, renal impact, cardiovascular impact, and quality of life
Time frame: At 1 year after first islet infusion and/or 1 year after final islet infusion
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 20 Oct 2017.
- National Institute of Allergy and Infectious Diseases (NIAID) websiteLink provided by the sponsor.
- Clinical Islet Transplantation Consortium websiteLink 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.
James F. Markmann, MD, PhD principal investigator
Massachusetts General Hospital
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Islet transplantation, Antithymocyte Globulin and Daclizumab or Basiliximab in people with Type 1 Diabetes Mellitus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 10 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 6 inclusion and 37 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 20 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 patients w/HbA1c </= to 6.5% and an absence of severe hypoglycemic events or a reduction in HbA1c of at least 1 point and an absence of severe hypoglycemic events (time frame: At 1 year after first islet infusion). 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 20 Oct 2017.