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

Phase 3

Completed

• Conditions: Diabetes Mellitus, Type 1
• Interventions: Biological: Islet Graft

• Registration Number: NCT01148680
• Lead Sponsor: University Hospital, Grenoble

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.

Study Timeline

• Study Start: 2010-06
• Study First Submitted: 2010-06-21
• Study First Submitted QC: 2010-06-21
• Study First Posted: 2010-06-22
• Primary Completion: 2018-08
• Study Completion: 2018-09
• Status Verified: 2019-04
• Last Update Submitted: 2020-01-24
• Last Update Posted: 2020-01-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
delayed registration on islet graft list	Islet Graft	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)
immediate registration on islet graft list	Islet Graft	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)

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (6)

University Hospital, Department of Endocrinology; 🇫🇷 Grenoble, Rhône-Alpes, France

University Hospital Gabriel Montpied, Department of Endocrinology; 🇫🇷 Clermont Ferrand, Auvergne, France

University Hospital Besançon, Department of Endocrinology; 🇫🇷 Besançon, Franche-Comté, France

University Hospital, Department of General Surgery and Endocrinology; 🇫🇷 Lille, Nord Pas De Calais, France

HCL Sud, Department of Endocrinology; 🇫🇷 Lyon, Rhône-Alpes, France

Hopitaux Universitaires de Genève, Department of Visceral Surgery and Transplant; 🇨🇭 Geneve, Switzerland