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

Diabetes Mellitus, Type 1 Clinical Trial

— TRIMECO  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01148680
• Other study ID #: DCIC 08 31
• Status: Completed
• Phase: Phase 3
• Start date: June 2010
• Est. completion date: September 2018

Study information

• Verified date: April 2019
• Source: University Hospital, Grenoble
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: September 2018
• Est. primary completion date: August 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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)

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1

Intervention

Biological:
• Islet Graft
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)

Locations

Country	Name	City	State
France	University Hospital Besançon, Department of Endocrinology	Besançon	Franche-Comté
France	University Hospital Gabriel Montpied, Department of Endocrinology	Clermont Ferrand	Auvergne
France	University Hospital, Department of Endocrinology	Grenoble	Rhône-Alpes
France	University Hospital, Department of General Surgery and Endocrinology	Lille	Nord Pas De Calais
France	HCL Sud, Department of Endocrinology	Lyon	Rhône-Alpes
France	University Hospital, Department of Endocrinology	Montpellier	Languedoc-Roussillon
France	University Hospital, Department of Endocrinology	Nancy	Lorraine
France	University Hospital, Department of Endocrinology	Strasbourg	Alsace
Switzerland	Hopitaux Universitaires de Genève, Department of Visceral Surgery and Transplant	Geneve

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Grenoble

Countries where clinical trial is conducted

France,  Switzerland, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Evaluation of metabolism indicators : ß-score and individual analysis of the 4 components of the ß-score	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	6 and 12 months
Secondary	Measure of quality of life (SF36, DQOL, DHP)	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	at inclusion time, at 6 months and at 12 months after first infusion (group 1) or after inclusion (group 2)
Secondary	Cost evaluation of islet cell infusion	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	6 months
Secondary	Evaluation of side effects and iatrogenic effects	Evaluation of side effects and iatrogenic effects at 6 months and 12 months after infusion	at 6 months and 12 months after infusion