Clinical trial NCT01148680: Trial Comparing Metabolic Efficiency of Islet Graft to Intensive Insulin Therapy for Type 1 Diabetes's 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 1
Keywords: Islet Cell Transplantation
Metabolic Diseases
Endocrine System Diseases
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
First posted: 2010-06-22
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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)

Primary outcomes:
measure: 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')
timeFrame: 6 months after first infusion (group 1) or 6 months after inclusion (group 2)
Secondary outcomes:
measure: Evaluation of metabolism indicators : ß-score and individual analysis of the 4 components of the ß-score
timeFrame: 6 and 12 months
measure: Measure of quality of life (SF36, DQOL, DHP)
timeFrame: at inclusion time, at 6 months and at 12 months after first infusion (group 1) or after inclusion (group 2)
measure: Cost evaluation of islet cell infusion
timeFrame: 6 months
measure: Evaluation of side effects and iatrogenic effects
timeFrame: at 6 months and 12 months after infusion
Other outcomes:
Locations:
city: Strasbourg
country: France
facility: University Hospital, Department of Endocrinology
state: Alsace
city: Clermont Ferrand
country: France
facility: University Hospital Gabriel Montpied, Department of Endocrinology
state: Auvergne
city: Besançon
country: France
facility: University Hospital Besançon, Department of Endocrinology
state: Franche-Comté
city: Montpellier
country: France
facility: University Hospital, Department of Endocrinology
state: Languedoc-Roussillon
city: Nancy
country: France
facility: University Hospital, Department of Endocrinology
state: Lorraine
city: Lille
country: France
facility: University Hospital, Department of General Surgery and Endocrinology
state: Nord Pas De Calais
city: Grenoble
country: France
facility: University Hospital, Department of Endocrinology
state: Rhône-Alpes
city: Lyon
country: France
facility: HCL Sud, Department of Endocrinology
state: Rhône-Alpes
city: Geneve
country: Switzerland
facility: Hopitaux Universitaires de Genève, Department of Visceral Surgery and Transplant
Study officials:
affiliation: University Hospital, Grenoble
name: Pierre-Yves Benhamou, Pr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Alejandro R, Barton FB, Hering BJ, Wease S; Collaborative Islet Transplant Registry Investigators. 2008 Update from the Collaborative Islet Transplant Registry. Transplantation. 2008 Dec 27;86(12):1783-8. doi: 10.1097/TP.0b013e3181913f6a.
citation: Shapiro AM, Ricordi C, Hering BJ, Auchincloss H, Lindblad R, Robertson RP, Secchi A, Brendel MD, Berney T, Brennan DC, Cagliero E, Alejandro R, Ryan EA, DiMercurio B, Morel P, Polonsky KS, Reems JA, Bretzel RG, Bertuzzi F, Froud T, Kandaswamy R, Sutherland DE, Eisenbarth G, Segal M, Preiksaitis J, Korbutt GS, Barton FB, Viviano L, Seyfert-Margolis V, Bluestone J, Lakey JR. International trial of the Edmonton protocol for islet transplantation. N Engl J Med. 2006 Sep 28;355(13):1318-30. doi: 10.1056/NEJMoa061267.
citation: Badet L, Benhamou PY, Wojtusciszyn A, Baertschiger R, Milliat-Guittard L, Kessler L, Penfornis A, Thivolet C, Renard E, Bosco D, Morel P, Morelon E, Bayle F, Colin C, Berney T; GRAGIL Group. Expectations and strategies regarding islet transplantation: metabolic data from the GRAGIL 2 trial. Transplantation. 2007 Jul 15;84(1):89-96. doi: 10.1097/01.tp.0000268511.64428.d8.
citation: Vantyghem MC, Kerr-Conte J, Arnalsteen L, Sergent G, Defrance F, Gmyr V, Declerck N, Raverdy V, Vandewalle B, Pigny P, Noel C, Pattou F. Primary graft function, metabolic control, and graft survival after islet transplantation. Diabetes Care. 2009 Aug;32(8):1473-8. doi: 10.2337/dc08-1685.
citation: Ryan EA, Paty BW, Senior PA, Lakey JR, Bigam D, Shapiro AM. Beta-score: an assessment of beta-cell function after islet transplantation. Diabetes Care. 2005 Feb;28(2):343-7. doi: 10.2337/diacare.28.2.343.
citation: Bahougne T, Olagne J, Munch M, Braun-Parvez L, Chenard MP, Fremeaux-Bacchi V, Caillard S, Baltzinger P, Greget M, Kessler L, Moulin B. Atypical hemolytic and uremic syndrome due to C3 mutation in pancreatic islet transplantation: a case report. BMC Nephrol. 2020 Sep 19;21(1):405. doi: 10.1186/s12882-020-02062-7.
citation: Lo C, Toyama T, Oshima M, Jun M, Chin KL, Hawley CM, Zoungas S. Glucose-lowering agents for treating pre-existing and new-onset diabetes in kidney transplant recipients. Cochrane Database Syst Rev. 2020 Jul 30;8(8):CD009966. doi: 10.1002/14651858.CD009966.pub3.
citation: Lablanche S, Vantyghem MC, Kessler L, Wojtusciszyn A, Borot S, Thivolet C, Girerd S, Bosco D, Bosson JL, Colin C, Tetaz R, Logerot S, Kerr-Conte J, Renard E, Penfornis A, Morelon E, Buron F, Skaare K, Grguric G, Camillo-Brault C, Egelhofer H, Benomar K, Badet L, Berney T, Pattou F, Benhamou PY; TRIMECO trial investigators. Islet transplantation versus insulin therapy in patients with type 1 diabetes with severe hypoglycaemia or poorly controlled glycaemia after kidney transplantation (TRIMECO): a multicentre, randomised controlled trial. Lancet Diabetes Endocrinol. 2018 Jul;6(7):527-537. doi: 10.1016/S2213-8587(18)30078-0. Epub 2018 May 15.