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

Type 1 Diabetes Mellitus Clinical Trial

Official title:

Transplantation d'Ilots Pancreatiques Allogeniques Adultes Pour le Traitement du Diabete Insulino-dependant: Etude GRAGIL 2.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00321256
• Other study ID #: 011226/DGS-2001/0195
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: May 2, 2006
• Last updated: March 1, 2012
• Start date: July 2003
• Est. completion date: July 2007

Study information

• Verified date: March 2012
• Source: University Hospital, Grenoble
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: July 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Procedure:
• human pancreatic islet transplantation

Locations

Country	Name	City	State
France	University Hospital, Department of Endocrinology	Besancon
France	University Hospital, Department of Endocrinology	Grenoble
France	University Hospital, Department of Endocrinology	Lyon
France	University Hospital, Department of Endocrinology	Montpellier
France	University Hospital, Department of Endocrinology	Strasbourg
Switzerland	University Hospital, Department of Surgery	Geneva

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Grenoble	Alfediam

Countries where clinical trial is conducted

France,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The rate of insulin-independence, judged upon the following criteria : HbA1c < 6.1%,
Primary	post-prandial blood glucose < 180 mg/dl, mean amplitude of glycemic excursion (MAGE index)
Primary	< 60 mg/dl, basal C-peptide > 0.5 ng/ml. This insulin independent rate will be assessed 6 months
Primary	and 12 months following transplantation.
Secondary	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;
Secondary	good metabolic control, defined by HbA1c = 6.5%; disappearance of hypoglycemic events; reduction in exogenous insulin needs = 30%.
Secondary	Morbidity and quality of life will also be assessed.