Status:
COMPLETED
Efficacy of Islet After Kidney Transplantation
Lead Sponsor:
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborating Sponsors:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Conditions:
Type 1 Diabetes Mellitus
Eligibility:
All Genders
18-68 years
Phase:
PHASE3
Brief 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 o...
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-...
Eligibility Criteria
Inclusion
- 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%.
Exclusion
- 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;
- 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.
Key Trial Info
Start Date :
January 1 2007
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
July 5 2017
Estimated Enrollment :
24 Patients enrolled
Trial Details
Trial ID
NCT00468117
Start Date
January 1 2007
End Date
July 5 2017
Last Update
October 20 2017
Active Locations (10)
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1
University of California, San Francisco
San Francisco, California, United States, 94143
2
University of Miami
Miami, Florida, United States, 33124
3
Emory Universtiy
Atlanta, Georgia, United States, 30322
4
Northwestern University
Chicago, Illinois, United States, 60208