Trial Comparing Metabolic Efficiency of Islet Graft to Intensive Insulin Therapy for Type 1 Diabetes's Treatment (TRIMECO)

Grenoble Alpes University Hospital Center (CHU)

Status and phase: Completed; Phase 3

Conditions: Diabetes Mellitus, Type 1

Treatments: Biological: Islet Graft

Study type: Interventional

Funder types: Other

Identifiers

NCT01148680

DCIC 08 31

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 patients

Sex: All

Ages: 18 to 64 years old

Volunteers: No Healthy Volunteers

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

• Exclusion criteria non-specifically related to islet infusion: evolutive vascular disease, evolutive cardiopathy (especially myocardial infarction less than 6 months ago, cerebrovascular stroke less than 6 months ago, evolutive arteritis with trophic disorders) ; systemic infection including hepatitis C and HIV ; leuconeutropenia ; thrombocytopenia, non-stabilized neoplastic pathology ; pregnancy or project of pregnancy within the next 24 months ; poor therapeutic compliance

• Criteria related to immunosuppressive protocol : renal failure (glomerular filtration < 35 ml/min/1.73 m²) and/or proteinuria > 0.5 g/24h ; non-treated hyperlipidemia (LDL-C > 130 mg/dL) ; blood pressure > 160/100 mmHg

• Clinical insulin resistance : assessed by patient's weight, BMI and exogenous insulin requirements (BMI > 30 kg/m² or insulin dose > 0.85 UI/kg/day)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

50 participants in 2 patient groups

immediate registration on islet graft list

Experimental group

Description:

group 1 'immediate registration on infusion waiting list' : patients who will be immediately registrated on islet cell infusion waiting list after randomization. Intervention : Procedure/surgery (islet graft)

Treatment:

Biological: Islet Graft

delayed registration on islet graft list

Active Comparator group

Description:

group 2 'delayed registration on infusion waiting list' : patients who will be registrated 6 months later on islet cell infusion waiting list after randomization. Intervention : Procedure/surgery (islet graft)

Treatment:

Biological: Islet Graft