Patients With Type 1 Diabetes
Conditions
Keywords
diabetes, transplantation
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.
Interventions
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Obtaining an improvement in glycemic control | within 2 years after inclusion | HbA1c \<6.5%, with lower insulin doses by 30% |
| 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%. |
| Improved metabolic profile determined by the OGTT and hyperglycemic clamp | within 2 years after inclusion | — |
| Decreased glycemic variability | within 2 years after inclusion | defined on blood glucose and / or glucose holter |
| Reduction of oxidative stress assessed by the urinary excretion of 24 hours of 8-iso-PGF2 rates. | within 2 years after inclusion | — |
| Restoration of normal glycemic control without insulin for a year | 1 year | — |
| quality of life | within 2 years after inclusion | defined by questionnaires DQOL and SF-36 |
| term graft survival | within 2 years of inclusion | defined by the rate of C-peptide |
| beta-cell function | 2 years | based on beta-score |
| 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 |
| degenerative complications of diabetes | 2 years | — |
| Decrease in the frequency, severity or poor perception of hypoglycaemia defined Hypo score | within the 2 years after inclusion | — |
Countries
France
Contacts
Primary ContactPierre CATTAN, MD PhD
Outcome results
None listed