Working… Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01974674
Recruitment Status : Recruiting
First Posted : November 1, 2013
Last Update Posted : September 29, 2016
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Patients With Type 1 Diabetes Procedure: Allogeneic transplantation of intrahepatic islet Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 19 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Allogeneic Islet Transplantation for the Treatment of Type 1 Diabetes
Study Start Date : July 2013
Estimated Primary Completion Date : December 2016
Estimated Study Completion Date : January 2022

Resource links provided by the National Library of Medicine

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

Primary Outcome Measures :
  1. restoration of normal glycemic control without insulin [ Time Frame: 6 months after graft ]

    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.

Secondary Outcome Measures :
  1. Restoration of normal glycemic control without insulin for a year [ Time Frame: 1 year ]
  2. Obtaining an improvement in glycemic control [ Time Frame: within 2 years after inclusion ]
    HbA1c <6.5%, with lower insulin doses by 30%

  3. Obtaining a remission of diabetes [ Time Frame: within 2 years after inclusion ]

    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%.

  4. Improved metabolic profile determined by the OGTT and hyperglycemic clamp [ Time Frame: within 2 years after inclusion ]
  5. Decreased glycemic variability [ Time Frame: within 2 years after inclusion ]
    defined on blood glucose and / or glucose holter

  6. Reduction of oxidative stress assessed by the urinary excretion of 24 hours of 8-iso-PGF2 rates. [ Time Frame: within 2 years after inclusion ]
  7. Decrease in the frequency, severity or poor perception of hypoglycaemia defined Hypo score [ Time Frame: within the 2 years after inclusion ]
  8. quality of life [ Time Frame: within 2 years after inclusion ]
    defined by questionnaires DQOL and SF-36

  9. term graft survival [ Time Frame: within 2 years of inclusion ]
    defined by the rate of C-peptide

  10. beta-cell function [ Time Frame: 2 years ]
    based on beta-score

  11. potential of each infusion of islets [ Time Frame: within 2 years after inclusion ]
    number of IEQ/kg of recipient required to reduce the daily insulin dose of 1 unit

  12. degenerative complications of diabetes [ Time Frame: 2 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01974674

Layout table for location contacts
Contact: Pierre CATTAN, MD PhD 33 1 42494786

Layout table for location information
Saint Louis hospital Recruiting
Paris, Ile de France, France, 75010
Contact: Pierre CATTAN, MD PhD    33 1 42494786   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Layout table for additonal information
Responsible Party: Assistance Publique - Hôpitaux de Paris Identifier: NCT01974674    
Other Study ID Numbers: P030415
First Posted: November 1, 2013    Key Record Dates
Last Update Posted: September 29, 2016
Last Verified: September 2016
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Additional relevant MeSH terms:
Layout table for MeSH terms
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases