Status:

COMPLETED

Human Islet Transplantation in Brittle Type 1 Diabetes Mellitus. The GRAGIL 2 Study.

Lead Sponsor:

University Hospital, Grenoble

Collaborating Sponsors:

Alfediam

Conditions:

Type 1 Diabetes Mellitus

Eligibility:

All Genders

18-65 years

Phase:

PHASE1

PHASE2

Brief Summary

This research project is supported by a multicentric network of collaborators whose goal is to assess the efficacy of transplanting allogenic pancreas islets to restore insulin secretion in patients w...

Detailed Description

The general objective is to demonstrate the beneficial effect of islet allotransplantation in patients with brittle type 1 diabetes with no endogenous insulin secretion, for whom the risk of the spont...

Eligibility Criteria

Inclusion

  • Inclusion criteria:
  • Type 1 diabetes mellitus
  • Disease duration \> 5 years
  • Despite intensive insulin therapy with tight endocrinologist supervision, persistence of the following conditions : hypoglycemia unawareness (\< 54 mg/dl) ; brittleness with at least two episodes of severe hypoglycemia ((defined by the need for assistance to correct the blood glucose level) or ketoacidosis per year , or often enough that the diabetologist judges the frequency to be life-threatening, the risk of transplantation and immunosuppression being judged to be less than the risk of the spontaneous course of uncontrolled diabetes
  • Basal and stimulated plasma C-peptide \< 0.2 ng/ml
  • Creatinine clearance ≥ 50 ml/min/1.73 m2 and proteinuria \< 0.5 g/24h
  • Exclusion criteria:
  • Severe cardiovascular disease (recent myocardial infarction, unstable coronaropathy…)
  • Severe systemic infection, including hepatitis C or B viral infection, HIV infection or tuberculosis
  • Past or present neoplasia (with the exception of non melanoma skin cancers)
  • Body weight \> 70 kg in women and BW \> 75 kg in men or BMI \> 26
  • Stimulated C-peptide ≥ 0.3 ng/ml upon Glucagon or Arginine stimulation
  • Age \< 18 years or \> 65 years
  • Creatinine clearance \< 50 ml/min/1.73 m2
  • Albuminuria \> 300 mg /24h or proteinuria \> 0.5 g/24h
  • Hemoglobinemia \< 120 g/l in women or \< 130 g/l in men
  • Liver disease (enzymes \> 1.5 N) such as cirrhosis or hepatitis
  • Liver hemangioma
  • Untreated proliferating diabetic retinopathy
  • Pregnancy, lactation, pregnancy project or absence of efficient contraception
  • Previous transplantation or immunization as judged by anti-HLA antibodies (\> 20%)
  • Insulin needs \> 0.7 IU/kg/d or \> 50 IU
  • HbA1c \> 12 %
  • Any medical condition needing the chronic use of steroids
  • Addison disease
  • Any hemostasis disorder needing a prolonged treatment with anticoagulation drugs. Low-dose aspirin is permitted. coagulation disorders contraindicating the procedure, such as platelet count \< 100000/mm3.
  • Serious life-threatening disease
  • Medical or surgical history potentially influencing the absorption, distribution, metabolism and clearance of drugs
  • Uncontrolled hypercholesterolemia (\> 350 mg/dl, 9.1 mmol/l) or hypertriglyceridemia (\> 500 mg/dl, 5.6 mmol/l)
  • Leukocytes \< 4500/mm3, neutrophils \< 2000/mm3, platelets \< 100000/mm3
  • Any medical or psychosocial condition susceptible to interfere with the study, such as drug abuse or recent alcohol abuse
  • Poor therapeutic observance
  • Failure to communicate or cooperate with the investigator

Exclusion

    Key Trial Info

    Start Date :

    July 1 2003

    Trial Type :

    INTERVENTIONAL

    End Date :

    July 1 2007

    Estimated Enrollment :

    22 Patients enrolled

    Trial Details

    Trial ID

    NCT00321256

    Start Date

    July 1 2003

    End Date

    July 1 2007

    Last Update

    March 2 2012

    Active Locations (6)

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    Page 1 of 2 (6 locations)

    1

    University Hospital, Department of Endocrinology

    Besançon, France, 25000

    2

    University Hospital, Department of Endocrinology

    Grenoble, France, 38043

    3

    University Hospital, Department of Endocrinology

    Lyon, France, 69000

    4

    University Hospital, Department of Endocrinology

    Montpellier, France, 34000