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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Grenoble
ClinicalTrials.gov Identifier:
NCT01148680
First received: June 21, 2010
Last updated: September 24, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type 1
Procedure: human pancreatic islet transplantation
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Controlled Trial Comparing the Metabolic Efficiency of Allogeneic Pancreatic Islet Transplantation to Intensive Insulin Therapy for the Treatment of Type 1 Diabetes

Resource links provided by NLM:


Further study details as provided by University Hospital, Grenoble:

Primary Outcome Measures:
  • 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') [ Time Frame: 6 months after first infusion (group 1) or 6 months after inclusion (group 2) ] [ Designated as safety issue: No ]
    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:
  • Evaluation of metabolism indicators : ß-score and individual analysis of the 4 components of the ß-score [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: at inclusion time, at 6 months and at 12 months after first infusion (group 1) or after inclusion (group 2) ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: at 6 months and 12 months after infusion ] [ Designated as safety issue: Yes ]
    Evaluation of side effects and iatrogenic effects at 6 months and 12 months after infusion


Estimated Enrollment: 40
Study Start Date: June 2010
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: immediate registration on infusion list
group 1 'immediate registration on infusion waiting list' : patients who will be immediately registrated on islet cell infusion waiting list after randomization
Procedure: human pancreatic islet transplantation
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)
delayed registration on infusion list
group 2 'delayed registration on infusion waiting list' : patients who will be registrated 6 months later on islet cell infusion waiting list after randomization
Procedure: human pancreatic islet transplantation
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)

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01148680

Locations
France
University Hospital, Department of Endocrinology
Strasbourg, Alsace, France, 67000
University Hospital Gabriel Montpied, Department of Endocrinology
Clermont Ferrand, Auvergne, France, 63003
University Hospital
Besançon, Franche-Comté, France, 25000
University Hospital, Department of Endocrinology
Montpellier, Languedoc-Roussillon, France, 34000
University Hospital, Department of Endocrinology
Nancy, Lorraine, France, 54000
University Hospital, Department of General Surgery and Endocrinology
Lille, Nord Pas de Calais, France, 59000
University Hospital, Department of Endocrinology
Grenoble, Rhône-Alpes, France, 38000
HCL Sud, Department of Endocrinology
Lyon, Rhône-Alpes, France, 69000
Switzerland
Hopitaux Universitaires de Genève
Geneve, Switzerland, CH-1211
Sponsors and Collaborators
University Hospital, Grenoble
Investigators
Principal Investigator: Pierre-Yves Benhamou, Pr University Hospital, Grenoble
  More Information

Publications:
Responsible Party: University Hospital, Grenoble
ClinicalTrials.gov Identifier: NCT01148680     History of Changes
Other Study ID Numbers: DCIC 08 31
Study First Received: June 21, 2010
Last Updated: September 24, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Grenoble:
Islet Cell Transplantation
Metabolic Diseases
Endocrine System Diseases

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on July 26, 2014