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

NCT01148680 | Completed Phase 3 DMC

• 1 other identifier: DCIC 08 31
• Study Type: interventional
• Target: 50
• Locations: 2 countries
• Sites: 9

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.

Conditions

Diabetes Mellitus, Type 1

Keywords

Islet Cell Transplantation; Metabolic Diseases; Endocrine System Diseases

Outcome Measures

Primary Outcomes (1)

• 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')

  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

  6 months after first infusion (group 1) or 6 months after inclusion (group 2)

Secondary Outcomes (4)

• Evaluation of metabolism indicators : ß-score and individual analysis of the 4 components of the ß-score

  6 and 12 months

• 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)

• Cost evaluation of islet cell infusion

  6 months

• Evaluation of side effects and iatrogenic effects

  at 6 months and 12 months after infusion

Study Arms (2)

immediate registration on islet graft list

EXPERIMENTAL

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)

Biological: Islet Graft

delayed registration on islet graft list

ACTIVE COMPARATOR

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)

Biological: Islet Graft

Interventions

Islet Graft BIOLOGICAL

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)

Also known as: human pancreatic islet transplantation

delayed registration on islet graft list; immediate registration on islet graft list

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• University Hospital, Grenoble: lead

Study Sites (9)

University Hospital, Department of Endocrinology

Strasbourg, Alsace, 67000, France

Location

University Hospital, Department of Endocrinology

Grenoble, Auvergne-Rhône-Alpes, 38000, France

Location

HCL Sud, Department of Endocrinology

Lyon, Auvergne-Rhône-Alpes, 69000, France

Location

University Hospital Gabriel Montpied, Department of Endocrinology

Clermont-Ferrand, Auvergne, 63003, France

Location

University Hospital Besançon, Department of Endocrinology

Besançon, Franche-Comté, 25000, France

Location

University Hospital, Department of General Surgery and Endocrinology

Lille, Hauts-de-France, 59000, France

Location

University Hospital, Department of Endocrinology

Montpellier, Languedoc-Roussillon, 34000, France

Location

University Hospital, Department of Endocrinology

Nancy, Lorraine, 54000, France

Location

Hopitaux Universitaires de Genève, Department of Visceral Surgery and Transplant

Geneva, CH-1211, Switzerland

Location

Related Publications (8)

• 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.

  PMID: 19104422 BACKGROUND

• 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.

  PMID: 17005949 BACKGROUND

• 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.

  PMID: 17627243 BACKGROUND

• 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.

  PMID: 19638525 BACKGROUND

• 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.

  PMID: 15677790 BACKGROUND

• 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.

  PMID: 32950058 DERIVED

• 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.

  PMID: 32803882 DERIVED

• 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.

  PMID: 29776895 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Metabolic Diseases; Endocrine System Diseases

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Nutritional and Metabolic Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Pierre-Yves Benhamou, Pr

  University Hospital, Grenoble

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2010
• First Posted: June 22, 2010
• Study Start: June 1, 2010
• Primary Completion: August 1, 2018
• Study Completion: September 1, 2018
• Last Updated: January 27, 2020

Record last verified: 2019-04

Locations

FR (8); CH (1)