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

This study is currently recruiting participants.
Verified October 2013 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01974674
First received: October 28, 2013
Last updated: October 31, 2013
Last verified: October 2013
  Purpose

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 Intervention Phase
Patients With Type 1 Diabetes
Procedure: Allogeneic transplantation of intrahepatic islet
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Allogeneic Islet Transplantation for the Treatment of Type 1 Diabetes

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • restoration of normal glycemic control without insulin [ Time Frame: 6 months after graft ] [ Designated as safety issue: No ]

    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:
  • Restoration of normal glycemic control without insulin for a year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Obtaining an improvement in glycemic control [ Time Frame: within 2 years after inclusion ] [ Designated as safety issue: No ]
    HbA1c <6.5%, with lower insulin doses by 30%

  • Obtaining a remission of diabetes [ Time Frame: within 2 years after inclusion ] [ Designated as safety issue: No ]

    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%.


  • Improved metabolic profile determined by the OGTT and hyperglycemic clamp [ Time Frame: within 2 years after inclusion ] [ Designated as safety issue: No ]
  • Decreased glycemic variability [ Time Frame: within 2 years after inclusion ] [ Designated as safety issue: No ]
    defined on blood glucose and / or glucose holter

  • Reduction of oxidative stress assessed by the urinary excretion of 24 hours of 8-iso-PGF2 rates. [ Time Frame: within 2 years after inclusion ] [ Designated as safety issue: No ]
  • Decrease in the frequency, severity or poor perception of hypoglycaemia defined Hypo score [ Time Frame: within the 2 years after inclusion ] [ Designated as safety issue: Yes ]
  • quality of life [ Time Frame: within 2 years after inclusion ] [ Designated as safety issue: Yes ]
    defined by questionnaires DQOL and SF-36

  • term graft survival [ Time Frame: within 2 years of inclusion ] [ Designated as safety issue: Yes ]
    defined by the rate of C-peptide

  • beta-cell function [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    based on beta-score

  • potential of each infusion of islets [ Time Frame: within 2 years after inclusion ] [ Designated as safety issue: No ]
    number of IEQ/kg of recipient required to reduce the daily insulin dose of 1 unit

  • degenerative complications of diabetes [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 19
Study Start Date: July 2013
Estimated Study Completion Date: January 2021
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01974674

Contacts
Contact: Pierre CATTAN, MD PhD 33 1 42494786 pierre.cattan@sls.aphp.fr

Locations
France
Saint Louis hospital Recruiting
Paris, Ile de France, France, 75010
Contact: Pierre CATTAN, MD PhD    33 1 42494786    pierre.cattan@sls.aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01974674     History of Changes
Other Study ID Numbers: P030415
Study First Received: October 28, 2013
Last Updated: October 31, 2013
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
diabetes
transplantation

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on April 17, 2014