Type 1 Diabetes Mellitus
Conditions
Keywords
islet transplantation, brittle diabetes, severe hypoglycemia, type 1 diabetes mellitus
Brief summary
This research project is supported by a multicentric network of collaborators whose goal is to assess the efficacy of transplanting allogenic pancreas islets to restore insulin secretion in patients with brittle type 1, insulin-dependent diabetes mellitus and to improve their metabolic control.
Detailed description
The general objective is to demonstrate the beneficial effect of islet allotransplantation in patients with brittle type 1 diabetes with no endogenous insulin secretion, for whom the risk of the spontaneous course of the disease is judged to be worse than the transplantation-related risk. The specific objective is to establish reference data for islet transplantation in non-uremic patients with brittle diabetes, in a multicentric network setting, using the Edmonton protocol.
Interventions
Sponsors
Alfediam
University Hospital, Grenoble
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Type 1 diabetes mellitus * Disease duration \> 5 years * Despite intensive insulin therapy with tight endocrinologist supervision, persistence of the following conditions : hypoglycemia unawareness (\< 54 mg/dl) ; brittleness with at least two episodes of severe hypoglycemia ((defined by the need for assistance to correct the blood glucose level) or ketoacidosis per year , or often enough that the diabetologist judges the frequency to be life-threatening, the risk of transplantation and immunosuppression being judged to be less than the risk of the spontaneous course of uncontrolled diabetes * Basal and stimulated plasma C-peptide \< 0.2 ng/ml * Creatinine clearance ≥ 50 ml/min/1.73 m2 and proteinuria \< 0.5 g/24h
Exclusion criteria
* Severe cardiovascular disease (recent myocardial infarction, unstable coronaropathy…) * Severe systemic infection, including hepatitis C or B viral infection, HIV infection or tuberculosis * Past or present neoplasia (with the exception of non melanoma skin cancers) * Body weight \> 70 kg in women and BW \> 75 kg in men or BMI \> 26 * Stimulated C-peptide ≥ 0.3 ng/ml upon Glucagon or Arginine stimulation * Age \< 18 years or \> 65 years * Creatinine clearance \< 50 ml/min/1.73 m2 * Albuminuria \> 300 mg /24h or proteinuria \> 0.5 g/24h * Hemoglobinemia \< 120 g/l in women or \< 130 g/l in men * Liver disease (enzymes \> 1.5 N) such as cirrhosis or hepatitis * Liver hemangioma * Untreated proliferating diabetic retinopathy * Pregnancy, lactation, pregnancy project or absence of efficient contraception * Previous transplantation or immunization as judged by anti-HLA antibodies (\> 20%) * Insulin needs \> 0.7 IU/kg/d or \> 50 IU * HbA1c \> 12 % * Any medical condition needing the chronic use of steroids * Addison disease * Any hemostasis disorder needing a prolonged treatment with anticoagulation drugs. Low-dose aspirin is permitted. coagulation disorders contraindicating the procedure, such as platelet count \< 100000/mm3. * Serious life-threatening disease * Medical or surgical history potentially influencing the absorption, distribution, metabolism and clearance of drugs * Uncontrolled hypercholesterolemia (\> 350 mg/dl, 9.1 mmol/l) or hypertriglyceridemia (\> 500 mg/dl, 5.6 mmol/l) * Leukocytes \< 4500/mm3, neutrophils \< 2000/mm3, platelets \< 100000/mm3 * Any medical or psychosocial condition susceptible to interfere with the study, such as drug abuse or recent alcohol abuse * Poor therapeutic observance * Failure to communicate or cooperate with the investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The rate of insulin-independence, judged upon the following criteria : HbA1c < 6.1%, | — |
| post-prandial blood glucose < 180 mg/dl, mean amplitude of glycemic excursion (MAGE index) | — |
| < 60 mg/dl, basal C-peptide > 0.5 ng/ml. This insulin independent rate will be assessed 6 months | — |
| and 12 months following transplantation. | — |
Secondary
| Measure | Time frame |
|---|---|
| good metabolic control, defined by HbA1c ≤ 6.5%; disappearance of hypoglycemic events; reduction in exogenous insulin needs ≥ 30%. | — |
| Morbidity and quality of life will also be assessed. | — |
| The rate of success according to the DiaCell composite score defined by the following 4 items : functional islet graft, defined by a basal C-peptide > 0.5 ng/ml; | — |
Countries
France, Switzerland
Outcome results
None listed