PRODIG (Prevention of new onset diabetes after transplantation by a short term treatment of Vildagliptin in the early renal post-transplant period) study: study protocol for a randomized controlled study

E. Gaiffe (1, 2, 3, 4) , T. Crépin (1, 2, 3, 4) , J. Bamoulid (1, 2, 3, 4) , C. Courivaud (1, 2, 3, 4) , M. Buchler (5) , E. Cassuto , L. Albano , J. M Chemouny (6) , Gabriel Choukroun (7, 8) , M. Hazzan (9, 10) , L. Kessler (11) , C. Legendre (12) , Y. Le Meur (13) , N. Ouali (14) , A. Thierry (15) , A. Anota (1, 2, 3, 4) , V. Nerich (2, 3, 4, 1) , S. Limat (3, 4, 1, 2) , F. Bonnetain (2, 3, 4, 1) , D. Vernerey (2, 3, 4, 1) , D. Ducloux (2, 3, 4, 1)

1 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
2 RIGHT - Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098)
3 UBFC - Université Bourgogne Franche-Comté [COMUE]
4 LabEx LipSTIC - Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer
5 Hôpital Bretonneau
6 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
7 CHU Amiens-Picardie
8 MP3CV - Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517
9 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
10 LIRIC - Lille Inflammation Research International Center - U 995
11 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
12 Hôpital Necker - Enfants Malades [AP-HP]
13 CHU - BREST - Nephrologie - CHRU Brest - Service de Nephrologie
14 CHU Tenon [AP-HP]
15 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital

BACKGROUND: Post-transplant diabetes is a frequent and serious complication of kidney transplantation. There is currently no treatment to prevent or delay the disease. Nevertheless, identification of risk factors make it possible to target a population at risk of developing de novo diabetes. We hypothesized that a short-term treatment with vildagliptin may prevent new onset diabetes after transplantation (NODAT) in high-risk patients. METHODS/DESIGN: This is a multicenter, double-blind, placebo-controlled randomized clinical trial. Patients undergoing first kidney transplantation will be included from ten French transplant centers. Included patients will be randomized (1:1) to receive either vildagliptin 100 or 50 mg/day (depending on glomerular filtration rate) during 2 months (the first dose being administered before entering the operating theatres) or placebo. Additional antidiabetic therapy could be administered according to glycemic control. The primary outcome is the proportion of diabetic patients 1 year after transplantation, defined as patients receiving a diabetic treatment, or having a fasting glucose above 7 mmol/l, and/or with an abnormal oral glucose tolerance test. Secondary outcomes include glycated hemoglobin, the occurrence of acute rejection, infection, graft loss and patient death at 3 months, 6 months, and 12 months after transplantation. Outcomes will be correlated to clinical and general characteristics of the patient, cardiovascular history, nephropathy, dialysis history, transplantation data, biological data, health-related quality of life, and the cost-effectiveness of prevention of diabetes with vildagliptin. DISCUSSION: We have scarce data on the pharmacological prevention of post-transplant diabetes. If our hypothesis is verified, our results will have a direct application in clinical practice and could limit diabetes-associated morbidity, reduce cardiovascular complications, increase quality of life of renal transplant patients, and consequently promote graft and patient survival. Our results may possibly serve for non-transplant patients carrying a high-risk of diabetes associated with other co-morbidities.

Mots clés: Diabetes prevention; Kidney transplantation; Randomized controlled trial; Vildagliptin

Domaines: Urologie et Néphrologie; Endocrinologie et métabolisme; Pharmacologie

E. Gaiffe, T. Crépin, J. Bamoulid, C. Courivaud, M. Buchler, et al.. PRODIG (Prevention of new onset diabetes after transplantation by a short term treatment of Vildagliptin in the early renal post-transplant period) study: study protocol for a randomized controlled study. Trials, 2019, 20 (1), pp.375. ⟨10.1186/s13063-019-3392-6⟩. ⟨hal-02173487⟩