Islet Allotransplantation With Steroid Free Immunosuppression

University Hospital, Lille

Status and phase: Completed; Phase 2

Conditions: Metabolic Diseases; Hypoglycemia; Type 1 Diabetes

Treatments: Procedure: islet transplantation; Drug: daclizumab - sirolimus - tacrolimus

Study type: Interventional

Funder types: Other

Identifiers

NCT00446264

PHRC

AFSSAPS 030209 (Other Identifier)

CP 01/48

Details and patient eligibility

About

The restoration of endogenous insulin secretion carries significant hopes for shifting the paradigm of life long exogenous insulin therapy in selected groups of patients with type 1 diabetes(T1D). After decades of frustrating clinical attempts, the Edmonton group set up in 2000 new standards for islet transplantation in patients with brittle T1D by achieving insulin independence in 80 percent of patients. These seminal results have however proved much more difficult to duplicate than initially expected.

This single center phase 2 clinical trial, duplicating the Edmonton protocol, is designed for confirming the consistent short term efficacy and safety of sequential islet allotransplantation with steroid free immunosuppression in patients with severe T1D.

Full description

The short term effectiveness of islet transplantation for alleviating hypoglycemia and controlling glucose homeostasis while limiting or even avoiding the nedd for exogenous insulin has been established despite protocol modifications in donor selection, islet preparation or recipient treatment, insulin independence with adequate metabolic control was however rarely prolonged beyond two years. The most frequently proposed explanations include chronic allogenic rejection, recurrence of autoimmunity and beta cell toxicity from administered immunosuppressive drugs.

Fourteen patients were enrolled in this single center phase 2 trial initiated in 2003. Eligible patients were males or females between 18 and 65 years of age, with type 1 diabeted documented for more than 5 years, arginine stimulated C-peptide lower than 0.2ng/ml, and hypoglycemia awareness or documented metabolic lability. Exclusion criteria included body mass index greater than 28Kg/m2, unstable arteriopathy or heart disease, active infection, previous transplantation, insulin daily requirements above 1.2 UI/kg, creatinin clearance below 60 ml/mn/m2 or urinary albumin excretion above 300 mg/day, malignancy, smoking, desire for pregnancy, psychiatric disorders and lack of compliance. The study primary efficacy endpoint was graft survival defined as insulin independence and HbA1c<6.5%. Secondary outcomes were graft function and metabolic control.

Enrollment: 14 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• type 1 diabetes documented for more than 5 years
• arginine stimulated C-peptide lower than 0.2 ng/mL
• one of the following:hypoglycemia unawareness OR metabolic lability documented by one or more severe hypoglycemias or two or more hospital admissions for ketoacidosis within the previous year.

Exclusion criteria

• body mass index greater than 28 kg/m2
• non stable arteriopathy or heart disease
• active infection
• previous transplantation
• hyperimmunization
• insulin daily needs above 1.2 U/Kg
• creatinine clearance below 60 ml/mn or urinary albumin excretion above 300 mg/d
• malignancy
• smoking
• desire for pregnancy
• psychiatric disorders
• lack of compliance

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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14 participants in 1 patient group

islet transplantation

Experimental group

Description:

Each participant received up to three sequential fresh islet infusions within three months.

Treatment:

Drug: daclizumab - sirolimus - tacrolimus

Procedure: islet transplantation