Allogeneic Islet Transplantation for the Treatment of Type 1 Diabetes
- Conditions
- Patients With Type 1 Diabetes
- Interventions
- Procedure: Allogeneic transplantation of intrahepatic islet
- Registration Number
- NCT01974674
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- Brief Summary
It is a multicentre, sequential, phase II clinical trial, aiming at evaluating the allogeneic islet transplantation for the treatment of type 1 diabetes.
19 patients with type 1 diabetes will be included and ideally distributed evenly: patients with unstable diabetes without renal insufficiency (AI group for "islet alone" by the international customary determination) and patients with a functioning kidney transplant (IAK group for "islet after kidney"). The main endpoint will be defined by the restoration of normal glycemic control without insulin at 6 months after graft.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 19
- Patients with type 1 diabetes
- 18 <Age <55 years
- Plasma C-peptide <0.2 ng/ml basal and stimulated glucagon
- Evolution of diabetes for more than 5 years
- Regular patient follow-up (> or equal to 2 visits per year from the same diabetologist)
- Patient who received the information and have given their consent in writing
- Absence of HIV, hepatitis B and hepatitis C, HTLV-1-2
- ABO compatibility with the donor
- Cross match negative
- Anti-HLA antibodies (class I and / or class II) detected by lymphocytotoxicity <20%
- PCR negative for the BK virus in the blood (so as not to amplify the BK virus replication with the ATG).
- Accepting patients effective contraception during the study period
For patients in group IA
-
Glomerular filtration rate estimated by the MDRD> 50 ml/min/1.73m2
-
No perception of hypoglycaemia (less than 0.54 mg/dl glucose) at least one value documented in the two years preceding and/or
-
Occurrence of at least one severe hypoglycemic episode (with a third required) and unexplained in the two years before and/or at least two episodes of ketoacidosis per year
-
Average HbA1c> 8.5% over two years, despite intensified treatment (basal pattern, bolus)
• For patients in the IAK
-
functional renal graft for at least 1 year
-
glomerular filtration rate> 50 ml/min/1.73 m2
-
proteinuria <0.5 g/day
-
Absence of acute rejection in renal previous 6 months
- BMI > 28
- Need insulin > 1 U/kg per day
- Pregnancy, lactation
- Intention of childbearing for the two sexes
- Psychiatric Disorders
- Inability to communicate or cooperate with the investigator
- Lack of therapeutic compliance, including HbA1C > 12%
- Chronic liver disease
- Progressive heart disease myocardial infarction within 6 months prior to inclusion, unbalanced CHD)
- Proliferative retinopathy unstabilized
- History of cancer, whatever the date, except for basal or squamous cell skin cancers over 1 year.
- Systemic infection
- Chronic high risk of requiring corticosteroids
- Need for long-term corticosteroid, outside that specified in renal transplantation, the patients will be weaned before transplantation
- Anticoagulant vitamin K or antiplatelet treatments
- Disorders of hemostasis TP <60 % TCA > 1.5 times the control
- Anti-HLA antibodies ( class I and/or class II ) detected by lymphocytotoxicity > 20%
- Platelets < 100 giga/L and/or neutrophils <1.5 giga/L
- Chronic intoxication by alcohol, tobacco, or other substance (abstinence > 6 months required)
- Active infection by hepatitis B, hepatitis C and HIV, HTLV-1-HTLV2
- Ascites
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Allogeneic transplantation of intrahepatic islet Allogeneic transplantation of intrahepatic islet Allogeneic transplantation of intrahepatic islet number required for insulin independence of obtaining, with a threshold dose of 9,000 IEQ/kg body weight of the recipient and a maximum sequence number of 3 infusions. The patient will receive after transplantation immunosuppressive therapy with Thymoglobulin for induction, Prograf and Cellcept, both of which are given throughout the duration of the study
- Primary Outcome Measures
Name Time Method restoration of normal glycemic control without insulin 6 months after graft the restoration of normal glycemic control without insulin therapy will be evaluated by measuring
- A fasting glucose (\> 8 hours) less than 1.25 g/L and a 2 hours glucose after oral intake of 75g of glucose, less than 2 g/L in a patient without insulin for at least 15 consecutive days during the the first 6 months from day 0.
- Secondary Outcome Measures
Name Time Method Decreased glycemic variability within 2 years after inclusion defined on blood glucose and / or glucose holter
term graft survival within 2 years of inclusion defined by the rate of C-peptide
potential of each infusion of islets within 2 years after inclusion number of IEQ/kg of recipient required to reduce the daily insulin dose of 1 unit
Obtaining a remission of diabetes within 2 years after inclusion The remission of diabetes is defined by the normality of blood glucose or insulin without lHbA1c.
The normality of blood glucose is defined below 1.20 g/L and postprandial fasting glycemia less than 1.60 g/L in the book self-monitoring (including 6/7 blood glucoses during the previous 3 days evaluation visit).
Normal HbA1c is defined as less than 6.5%.Decrease in the frequency, severity or poor perception of hypoglycaemia defined Hypo score within the 2 years after inclusion Restoration of normal glycemic control without insulin for a year 1 year Obtaining an improvement in glycemic control within 2 years after inclusion HbA1c \<6.5%, with lower insulin doses by 30%
quality of life within 2 years after inclusion defined by questionnaires DQOL and SF-36
beta-cell function 2 years based on beta-score
Improved metabolic profile determined by the OGTT and hyperglycemic clamp within 2 years after inclusion Reduction of oxidative stress assessed by the urinary excretion of 24 hours of 8-iso-PGF2 rates. within 2 years after inclusion degenerative complications of diabetes 2 years
Trial Locations
- Locations (1)
Saint Louis hospital
🇫🇷Paris, Ile de France, France