Metabolic Efficiency of Combined Pancreatic Islet and Lung Transplant for the Treatment of End-Stage Cystic Fibrosis (PIM)

Inclusion criteria:

• Age > 18
• Patient with cystic fibrosis
• Patient able to respect the protocol procedures
• Patient with end-stage respiratory insufficiency indicating a lung transplant
• Patient on insulin therapy
• Clinical history of cystic fibrosis related diabetes with no residual insulin secretion (C-peptide < 0,5 ng/mL) or no response to IV glucagon stimulation:

[peak stimulated C-peptide (T6min)/basal plasma C-peptide(T0)] < 2

• The absence of insulin secretion will be verified 2 times before inclusion
• Cystic fibrosis related diabetes duration > 3 years
• Patient whose glycaemic control obtained with insulin therapy is not satisfactory and could significantly alter quality of life (HbA1c > 7% and/or MAGE index > 1,25). This situation is assessed by a diabetologist.
• Social Security membership or benefit from Social Welfare
• Patient who received the results of the medical evaluation required

Exclusion criteria:

• Cystic fibrosis related diabetes duration < 3 years
• Patient with no contra-indication for undergo a lung transplant
• Patient under oral antidiabetic drug
• Criteria specifically related to the islet intraportal injection procedure:

haemostasis problem, abnormalities of complete blood count, documented liver pathology (alkaline phosphatases, gamma GT, transaminases levels over three times normal values); pancreatitis history, gallbladder stones that could potentially migrate; HLA hyperimmunisation (PRA > 20%).

• Portal hypertension identified by oesophageal varice and/or hypersplenism (platelets < 120 000 /mm3) or Child-Pugh score > 6.
• Exclusion criteria non-specifically related to islet infusion: evolutive vascular disease, evolutive cardiopathy (especially myocardial infarction less than 6 months ago, cerebrovascular stroke less than 6 months ago, evolutive arteritis with trophic disorders); systemic infection including hepatitis B or C and HIV ; leuconeutropenia (< 1 500/μL); thrombocytopenia (< 100 000/μL), non-stabilized neoplastic pathology; antecedent of breast cancer or melanoma; pregnancy or project of pregnancy within the next 24 months or current breast-feeding; poor therapeutic compliance
• Alcoholic intoxication or drug addiction
• Use of a medical treatment under investigation within one month before inclusion
• Patient restricted of freedom or unable to give his consent
• All medical situation assessed by an investigator which could interfere with the good management of the project