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

NCT ID: NCT01148680

Last Updated: 2020-01-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-06-30

Study Completion Date

2018-09-30

Brief Summary

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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

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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.

Conditions

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Diabetes Mellitus, Type 1

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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immediate registration on islet graft list

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)

Group Type EXPERIMENTAL

Islet Graft

Intervention Type 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)

delayed registration on islet graft 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.

Intervention : Procedure/surgery (islet graft)

Group Type ACTIVE_COMPARATOR

Islet Graft

Intervention Type 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)

Interventions

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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)

Intervention Type BIOLOGICAL

Other Intervention Names

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human pancreatic islet transplantation

Eligibility Criteria

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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
* 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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

64 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Grenoble

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pierre-Yves Benhamou, Pr

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Grenoble

Locations

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University Hospital, Department of Endocrinology

Strasbourg, Alsace, France

Site Status

University Hospital, Department of Endocrinology

Grenoble, Auvergne-Rhône-Alpes, France

Site Status

HCL Sud, Department of Endocrinology

Lyon, Auvergne-Rhône-Alpes, France

Site Status

University Hospital Gabriel Montpied, Department of Endocrinology

Clermont-Ferrand, Auvergne, France

Site Status

University Hospital Besançon, Department of Endocrinology

Besançon, Franche-Comté, France

Site Status

University Hospital, Department of General Surgery and Endocrinology

Lille, Hauts-de-France, France

Site Status

University Hospital, Department of Endocrinology

Montpellier, Languedoc-Roussillon, France

Site Status

University Hospital, Department of Endocrinology

Nancy, Lorraine, France

Site Status

Hopitaux Universitaires de Genève, Department of Visceral Surgery and Transplant

Geneva, , Switzerland

Site Status

Countries

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France Switzerland

References

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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.

Reference Type BACKGROUND
PMID: 19104422 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17005949 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17627243 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19638525 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15677790 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32950058 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32803882 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29776895 (View on PubMed)

Other Identifiers

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DCIC 08 31

Identifier Type: -

Identifier Source: org_study_id

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