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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 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: April 22, 2014
Last verified: April 2014
  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
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, see Learn About Clinical Studies.

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: April 22, 2014
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
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases

ClinicalTrials.gov processed this record on November 20, 2014