Clinical trial NCT00639600: Transplantation of Pancreatic Islets in Patients With Type 1 Diabetes Mellitus and Functional Kidney Graft
Official title: Transplantation d'îlots pancréatiques allogéniques Adultes Pour le Traitement du diabète insulinodépendant. Etude GRAGIL 1
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Type 1 Diabetes Mellitus
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
First posted: 2008-03-20
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed description: The main objective is to demonstrate the beneficial effect of islet allotransplantation in patients with type 1 diabetes with no endogenous insulin secretion, and with a functional kidney graft. The other objectives are to evaluate the conditions for the efficacy of islet cell transplantation, to assess the improvement in quality of life and the cost of the islet cell transplantation.

Eligibility criteria: Inclusion Criteria:

* Type 1 diabetes mellitus
* Disease duration \> 5 years
* ketose antecedents
* Basal and stimulated plasma C-\< 0.2 ng/ml,\<0.06 nmol/l (glycemia must be measured simultaneously_ 1.20 g/l or 6.6 mM, stimulation with glucagon IV 1 mg -Measured at à T0 and T 6 min)
* Established kidney graft ≥ 6 months
* Current creatinine clearance: ≥ 50 ml/min/1.73 m² and Proteinuria \< 0.5 g/24h
* HbA1C\< 12%

Exclusion Criteria:

* Hemostasis problems
* Documented hepatic pathology
* Patient under 18 or over 65 year-old
* Women with body weight over 70 kg (tolerance of 2 kg between inclusion day and transplantation day) or BMI \> 26
* Men with body weight \> 75 kg (tolerance of 3 kg between inclusion day and transplantation day) or BMI \> 26
* insuline needs \> 0.7 U/kg/j or 50 U/j
* Serious life-threatening pathology
* untreated hyperlipidemia
* Hypersensitivity to drugs rapamycine-alike
* Liver disease (transaminases or total bilirubin ≥ 3N)
* Failure to communicate or cooperate with the investigator

Exclusion criteria that are specific to the use of Rapamycine

* Hypercholesterolemia (\> 350mg/dl, 9,1 mmol/l) not controlled
* Hypertriglyceridemia (\> 500 mg/dl, 5,6 mmol/l) not controlled
* Leukocytes \> 4500 /mm3 , neutrophils \> 2000/ mm3, platelets \> 100000/ mm3
* Any clinical or biological pathology that could interfere with the study
* Past or present neoplasia (with the exception of non melanoma skin cancers)
* Any hemostasis disorder needing a prolonged treatment with anticoagulation drugs. Low-dose aspirin is permitted.
* Pregnancy, lactation, pregnancy project or absence of efficient contraception
* Any medical or psychosocial condition susceptible to interfere with the study, such as drug abuse or recent alcohol abuse

Primary outcomes:
measure: Rate of insulin-independence at 6 and 12 months after transplantation, duration of insulin-independence, survival curves
timeFrame: 12 months
Secondary outcomes:
measure: Tolerance (Measurement of portal pressure during islet injection) Quality of life (Questionnaires SF-36 and DQOL at inclusion time, then every 6 months during their waiting period and then 6 months and 12 months after transplantation) Costs
timeFrame: 12 months
Other outcomes:
Locations:
city: Besancon
country: France
facility: University Hospital
city: Grenoble
country: France
facility: University Hospital, Department of Endocrinology
city: Lyon
country: France
facility: University Hospital, Department of Endocrinology
city: Montpellier
country: France
facility: University Hospital, Department of Endocrinology
city: Nancy
country: France
facility: University Hospital, Department of Endocrinology
city: Strasbourg
country: France
facility: University Hospital, Department of Endocrinology
city: Geneva
country: Switzerland
facility: University Hospital, Department of Surgery
Study officials:
affiliation: University Hospital of Grenoble, Department of Endocrinology
name: Pierre Y Benhamou, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.