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

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.

Study Overview

• Status: Unknown
• Conditions: Patients With Type 1 Diabetes
• Intervention / Treatment: Procedure: Allogeneic transplantation of intrahepatic islet

• Study Type: Interventional
• Enrollment (Anticipated): 19
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Pierre CATTAN, MD PhD; Phone Number: 33 1 42494786; Email: pierre.cattan@sls.aphp.fr

Study Locations

• France
  • Ile de France
    • Paris, Ile de France, France, 75010
      • Recruiting
      • Saint Louis Hospital
      • Contact: Pierre CATTAN, MD PhD; Phone Number: 33 1 42494786; Email: pierre.cattan@sls.aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Allogeneic transplantation of intrahepatic islet; 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

Procedure: Allogeneic transplantation of intrahepatic islet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
restoration of normal glycemic control without insulin	the restoration of normal glycemic control without insulin therapy will be evaluated by measuring - A fasting glucose (> 8 hours) less than 1.25 g/L and a 2 hours glucose after oral intake of 75g of glucose, less than 2 g/L in a patient without insulin for at least 15 consecutive days during the the first 6 months from day 0.	6 months after graft

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Restoration of normal glycemic control without insulin for a year		1 year
Obtaining an improvement in glycemic control	HbA1c <6.5%, with lower insulin doses by 30%	within 2 years after inclusion
Obtaining a remission of diabetes	The remission of diabetes is defined by the normality of blood glucose or insulin without lHbA1c. The normality of blood glucose is defined below 1.20 g/L and postprandial fasting glycemia less than 1.60 g/L in the book self-monitoring (including 6/7 blood glucoses during the previous 3 days evaluation visit). Normal HbA1c is defined as less than 6.5%.	within 2 years after inclusion
Improved metabolic profile determined by the OGTT and hyperglycemic clamp		within 2 years after inclusion
Decreased glycemic variability	defined on blood glucose and / or glucose holter	within 2 years after inclusion
Reduction of oxidative stress assessed by the urinary excretion of 24 hours of 8-iso-PGF2 rates.		within 2 years after inclusion
Decrease in the frequency, severity or poor perception of hypoglycaemia defined Hypo score		within the 2 years after inclusion
quality of life	defined by questionnaires DQOL and SF-36	within 2 years after inclusion
term graft survival	defined by the rate of C-peptide	within 2 years of inclusion
beta-cell function	based on beta-score	2 years
potential of each infusion of islets	number of IEQ/kg of recipient required to reduce the daily insulin dose of 1 unit	within 2 years after inclusion
degenerative complications of diabetes		2 years

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (ANTICIPATED): December 1, 2016
• Study Completion (ANTICIPATED): January 1, 2022

Study Registration Dates

• First Submitted: October 28, 2013
• First Submitted That Met QC Criteria: October 31, 2013
• First Posted (ESTIMATE): November 1, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): September 29, 2016
• Last Update Submitted That Met QC Criteria: September 28, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: diabetes; transplantation
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: P030415