Allogeneic Islet Transplantation for the Treatment of Type 1 Diabetes (GRIIF)

Assistance Publique - Hôpitaux de Paris

Status and phase: Unknown; Phase 2

Conditions: Patients With Type 1 Diabetes

Treatments: Procedure: Allogeneic transplantation of intrahepatic islet

Study type: Interventional

Funder types: Other

Identifiers

NCT01974674

P030415

Details and patient eligibility

About

It is a multicentre, sequential, phase II clinical trial, aiming at evaluating the allogeneic islet transplantation for the treatment of type 1 diabetes.

19 patients with type 1 diabetes will be included and ideally distributed evenly: patients with unstable diabetes without renal insufficiency (AI group for "islet alone" by the international customary determination) and patients with a functioning kidney transplant (IAK group for "islet after kidney"). The main endpoint will be defined by the restoration of normal glycemic control without insulin at 6 months after graft.

Enrollment: 19 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with type 1 diabetes
• 18 <Age <55 years
• Plasma C-peptide <0.2 ng/ml basal and stimulated glucagon
• Evolution of diabetes for more than 5 years
• Regular patient follow-up (> or equal to 2 visits per year from the same diabetologist)
• Patient who received the information and have given their consent in writing
• Absence of HIV, hepatitis B and hepatitis C, HTLV-1-2
• ABO compatibility with the donor
• Cross match negative
• Anti-HLA antibodies (class I and / or class II) detected by lymphocytotoxicity <20%
• PCR negative for the BK virus in the blood (so as not to amplify the BK virus replication with the ATG).
• Accepting patients effective contraception during the study period

For patients in group IA

• Glomerular filtration rate estimated by the MDRD> 50 ml/min/1.73m2

• No perception of hypoglycaemia (less than 0.54 mg/dl glucose) at least one value documented in the two years preceding and/or

• Occurrence of at least one severe hypoglycemic episode (with a third required) and unexplained in the two years before and/or at least two episodes of ketoacidosis per year

• Average HbA1c> 8.5% over two years, despite intensified treatment (basal pattern, bolus)

  • For patients in the IAK

• functional renal graft for at least 1 year

• glomerular filtration rate> 50 ml/min/1.73 m2

• proteinuria <0.5 g/day

• Absence of acute rejection in renal previous 6 months

Exclusion criteria

• BMI > 28
• Need insulin > 1 U/kg per day
• Pregnancy, lactation
• Intention of childbearing for the two sexes
• Psychiatric Disorders
• Inability to communicate or cooperate with the investigator
• Lack of therapeutic compliance, including HbA1C > 12%
• Chronic liver disease
• Progressive heart disease myocardial infarction within 6 months prior to inclusion, unbalanced CHD)
• Proliferative retinopathy unstabilized
• History of cancer, whatever the date, except for basal or squamous cell skin cancers over 1 year.
• Systemic infection
• Chronic high risk of requiring corticosteroids
• Need for long-term corticosteroid, outside that specified in renal transplantation, the patients will be weaned before transplantation
• Anticoagulant vitamin K or antiplatelet treatments
• Disorders of hemostasis TP <60 % TCA > 1.5 times the control
• Anti-HLA antibodies ( class I and/or class II ) detected by lymphocytotoxicity > 20%
• Platelets < 100 giga/L and/or neutrophils <1.5 giga/L
• Chronic intoxication by alcohol, tobacco, or other substance (abstinence > 6 months required)
• Active infection by hepatitis B, hepatitis C and HIV, HTLV-1-HTLV2
• Ascites

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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19 participants in 1 patient group

Allogeneic transplantation of intrahepatic islet

Experimental group

Description:

Allogeneic transplantation of intrahepatic islet number required for insulin independence of obtaining, with a threshold dose of 9,000 IEQ/kg body weight of the recipient and a maximum sequence number of 3 infusions. The patient will receive after transplantation immunosuppressive therapy with Thymoglobulin for induction, Prograf and Cellcept, both of which are given throughout the duration of the study

Treatment:

Procedure: Allogeneic transplantation of intrahepatic islet