Diabetes Mellitus, Type 1
Conditions
Keywords
Islet Cell Transplantation, Metabolic Diseases, Endocrine System Diseases
Brief summary
Efficacy of pancreatic islet transplantation at 6 months compared to an intensive insulin therapy for 2 categories of patients: patients with unstable diabetes and patients who underwent kidney transplantation.
Detailed description
Efficacy of pancreatic islet transplantation at 6 months compared to an intensive insulin therapy for 2 categories of patients: patients with unstable type 1 diabetes versus patients with unstable type 1 diabetes and who underwent kidney transplantation.
Interventions
BIOLOGICALIslet Graft
Iterative injection of pancreatic islets (minimum: 250,000 IEQ / injection or 3500 IEQ / kg / injection) with a threshold required total of 11,000 IEQ / kg in 2 or 3 injections per patient)
Sponsors
University Hospital, Grenoble
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Patient with type 1 diabetes or C-peptide negative diabetes Diabetes duration \> 5 years * No residual insulin secretion (plasmatic basal and stimulated C-peptide \< 0.3 ng/ml) * HbA1c considered acceptable by the selection committee * Insulin needs \< 0.85 IU/kg/day * Islet cell infusion after kidney graft * Patient with terminal renal failure and functional kidney graft for at least 6 months (creatinine clearance greater than or equal to 35 ml/min) * Patient whose glycaemic control obtained with insulin therapy could threaten kidney graft survival and/or significantly alter quality of life. This situation is assessed by a diabetologist * Islet cell infusion only: patient with major glycaemic variability despite proper intensive insulin therapy, closely monitored by a diabetologist. Poor glucose control, assessed by a diabetologist, endangers the patient's life and/or significantly alters personal, social, professional and family quality of life. At least one of these criteria must be fulfilled : * Hypoglycaemia unawareness, blood glucose level \< 3mmol/L or 0.54 mg/L * At least 2 severe hypoglycaemia events (defined by the necessity of a third party's assistance) per year or a ketoacidosis requiring patient's hospitalization during the last year. * Impairment of quality of life or life-threat for patient or other persons, or progressive complications despite optimal insulin therapy * Social Security membership or benefit from Social Welfare
Exclusion criteria
* Age\< 18 and \> 65 * Diabetes duration \< 5 years * Criteria specifically related to the islet intraportal injection procedure: hemostasis problem, haemoglobin level \< 11g/dL for women and \<12g/dL for men, abnormalities of complete blood count, documented liver pathology (alkaline phosphatases, gamma GT, transaminases levels over twice normal values) ; pancreatitis history, gallbladder stones that could potentially migrate; HLA hyperimmunisation (PRA \>20%). * Criteria related to diabetes complications : * Non-stabilized proliferating diabetic retinopathy * Creatininaemia \> 16 mg/dL *
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ß score evaluation 6 months after first infusion (group 1 'immediate registration on infusion waiting list') or 6 months after inclusion (group 2: 'delayed registration on infusion waiting list') | 6 months after first infusion (group 1) or 6 months after inclusion (group 2) | Metabolism evaluated by ß score. This score uses 4 intermediate scores ranging from 0 to 2 associated with the following 4 indicators: HbA1c, basal C peptide (or stimulated C-peptide), daily insulin dose (U/kg) or intake of oral antidiabetic drugs and fasting glycaemia. The total of the intermediate scores ranges from 0 to 8. Islet graft will be considered as successful if the ß score is equal to or greater than 6 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of metabolism indicators : ß-score and individual analysis of the 4 components of the ß-score | 6 and 12 months | Metabolism indicators at 6 and 12 months : ß-score (quantitative analysis by mean score comparison), individual analysis of the 4 components of the ß-score (HbA1c, basal C peptide (or stimulated C-peptide), daily insulin dose (U/kg) or intake of oral antidiabetic drugs and fasting glycaemia), lability index, ADRR score, Clarke score |
| Measure of quality of life (SF36, DQOL, DHP) | at inclusion time, at 6 months and at 12 months after first infusion (group 1) or after inclusion (group 2) | Measure of quality of life (SF36, DQOL, DHP) for Group 1 ('immediate registration on infusion waiting list'): at inclusion time, at 6 months and at 12 months after first infusion For Group 2 ('delayed registration on infusion waiting list'): at inclusion time, 6 months after inclusion, at 6 months and at 12 months after first infusion |
| Cost evaluation of islet cell infusion | 6 months | Cost comparison between islet cell infusion (group 1 'immediate registration on infusion waiting list')and intensive insulin therapy (group 2 'delayed registration on infusion waiting list') at 6 months, from a hospital perspective as well as a health-insurance system perspective |
| Evaluation of side effects and iatrogenic effects | at 6 months and 12 months after infusion | Evaluation of side effects and iatrogenic effects at 6 months and 12 months after infusion |
Countries
France, Switzerland
Outcome results
None listed