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

NCT ID: NCT00321256

Last Updated: 2012-03-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-07-31
• Study Completion Date: 2007-07-31

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

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.

Conditions

Type 1 Diabetes Mellitus

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

human pancreatic islet transplantation

Intervention Type: PROCEDURE

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alfediam

OTHER

Sponsor Role: collaborator

University Hospital, Grenoble

OTHER

Sponsor Role: lead

Principal Investigators

Pierre Y Benhamou, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Universty Hospital, Grenoble, France

Philippe Morel, MD, PhD

Role: STUDY_CHAIR

University Hospital, Geneva, Switzerland

Charles Thivolet, MD, PhD

Role: STUDY_DIRECTOR

Hospices Civils de Lyon

Alfred Penfornis, MD, PhD

Role: STUDY_DIRECTOR

University Hospital, Besancon, France

Laurence Kessler, MD, PhD

Role: STUDY_DIRECTOR

University Hospital, Strasbourg, France

Eric Renard, MD, PhD

Role: STUDY_DIRECTOR

University Hospital, Montpellier France

Lionel Badet, MD, PhD

Role: STUDY_DIRECTOR

Hospices Civils de Lyon

Cyrille Colin, MD, PhD

Role: STUDY_DIRECTOR

Hospices Civils de Lyon

Thierry Berney, MD, PhD

Role: STUDY_DIRECTOR

University Hospital, Geneva, Switzerland

Locations

University Hospital, Department of Endocrinology

Besançon, , 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, , France

University Hospital, Department of Surgery

Geneva, , Switzerland

Countries

France; Switzerland

References

Lablanche S, Borot S, Wojtusciszyn A, Bayle F, Tetaz R, Badet L, Thivolet C, Morelon E, Frimat L, Penfornis A, Kessler L, Brault C, Colin C, Tauveron I, Bosco D, Berney T, Benhamou PY; GRAGIL Network. Five-Year Metabolic, Functional, and Safety Results of Patients With Type 1 Diabetes Transplanted With Allogenic Islets Within the Swiss-French GRAGIL Network. Diabetes Care. 2015 Sep;38(9):1714-22. doi: 10.2337/dc15-0094. Epub 2015 Jun 11.

Reference Type: DERIVED

PMID: 26068866 (View on PubMed)

Other Identifiers

011226/DGS-2001/0195

Identifier Type: -

Identifier Source: org_study_id