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

May 2, 2006
March 1, 2012
July 2003
Not Provided
  • 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.
Same as current
Complete list of historical versions of study NCT00321256 on ClinicalTrials.gov Archive Site
  • 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.
Same as current
Not Provided
Not Provided
 
Human Islet Transplantation in Brittle Type 1 Diabetes Mellitus. The GRAGIL 2 Study.
Transplantation d'Ilots Pancreatiques Allogeniques Adultes Pour le Traitement du Diabete Insulino-dependant: Etude GRAGIL 2.

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.

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.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Type 1 Diabetes Mellitus
Procedure: human pancreatic islet transplantation
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
22
July 2007
Not Provided

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
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
France,   Switzerland
 
NCT00321256
011226/DGS-2001/0195
Not Provided
Not Provided
University Hospital, Grenoble
Alfediam
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
University Hospital, Grenoble
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP