Human Islet Transplantation in Brittle Type 1 Diabetes Mellitus. The GRAGIL 2 Study.

Grenoble Alpes University Hospital Center (CHU)

Status and phase

Completed

Phase 2

Phase 1

Conditions

Type 1 Diabetes Mellitus

Treatments

Procedure: human pancreatic islet transplantation

Study type

Interventional

Funder types

Other

Identifiers

NCT00321256

011226/DGS-2001/0195

Details and patient eligibility

About

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.

Full 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.

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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