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

This study has been completed.
Sponsor:
Collaborator:
Alfediam
Information provided by:
University Hospital, Grenoble
ClinicalTrials.gov Identifier:
NCT00321256
First received: May 2, 2006
Last updated: March 1, 2012
Last verified: March 2012
  Purpose

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 with brittle type 1, insulin-dependent diabetes mellitus and to improve their metabolic control.


Condition Intervention Phase
Type 1 Diabetes Mellitus
Procedure: human pancreatic islet transplantation
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Transplantation d'Ilots Pancreatiques Allogeniques Adultes Pour le Traitement du Diabete Insulino-dependant: Etude GRAGIL 2.

Resource links provided by NLM:


Further study details as provided by University Hospital, Grenoble:

Primary Outcome Measures:
  • The rate of insulin-independence, judged upon the following criteria : HbA1c < 6.1%,
  • post-prandial blood glucose < 180 mg/dl, mean amplitude of glycemic excursion (MAGE index)
  • < 60 mg/dl, basal C-peptide > 0.5 ng/ml. This insulin independent rate will be assessed 6 months
  • and 12 months following transplantation.

Secondary Outcome Measures:
  • The rate of success according to the DiaCell composite score defined by the following 4 items : functional islet graft, defined by a basal C-peptide > 0.5 ng/ml;
  • good metabolic control, defined by HbA1c ≤ 6.5%; disappearance of hypoglycemic events; reduction in exogenous insulin needs ≥ 30%.
  • Morbidity and quality of life will also be assessed.

Estimated Enrollment: 22
Study Start Date: July 2003
Study Completion Date: July 2007
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 spontaneous course of the disease is judged to be worse than the transplantation-related risk. The specific objective is to establish reference data for islet transplantation in non-uremic patients with brittle diabetes, in a multicentric network setting, using the Edmonton protocol.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00321256

Locations
France
University Hospital, Department of Endocrinology
Besancon, France, 25000
University Hospital, Department of Endocrinology
Grenoble, France, 38043
University Hospital, Department of Endocrinology
Lyon, France, 69000
University Hospital, Department of Endocrinology
Montpellier, France, 34000
University Hospital, Department of Endocrinology
Strasbourg, France, 66000
Switzerland
University Hospital, Department of Surgery
Geneva, Switzerland, 1211
Sponsors and Collaborators
University Hospital, Grenoble
Alfediam
Investigators
Principal Investigator: Pierre Y Benhamou, MD, PhD Universty Hospital, Grenoble, France
Study Chair: Philippe Morel, MD, PhD University Hospital, Geneva, Switzerland
Study Director: Charles Thivolet, MD, PhD Hospices Civils de Lyon
Study Director: Alfred Penfornis, MD, PhD University Hospital, Besancon, France
Study Director: Laurence Kessler, MD, PhD University Hospital, Strasbourg, France
Study Director: Eric Renard, MD, PhD University Hospital, Montpellier, France
Study Director: Lionel Badet, MD, PhD Hospices Civils de Lyon
Study Director: Cyrille Colin, MD, PhD Hospices Civils de Lyon
Study Director: Thierry Berney, MD, PhD University Hospital, Geneva, Switzerland
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00321256     History of Changes
Other Study ID Numbers: 011226/DGS-2001/0195
Study First Received: May 2, 2006
Last Updated: March 1, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Grenoble:
islet transplantation
brittle diabetes
severe hypoglycemia
type 1 diabetes mellitus

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 October 16, 2014