Clinical trial NCT02849899: Prevention of Diabetes After Transplantation by Vildagliptin in the Early Post-transplant Period
Official title: Prevention of New Onset Diabetes After Transplantation by a Short Term Treatment of Vildagliptin in the Early Post-transplant Period
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Disorder Related to Renal Transplantation
Diabetes
Lead sponsor: Centre Hospitalier Universitaire de Besancon
Sponsor class: OTHER
Collaborators: name: University Hospital, Tours
name: University Hospital, Lille
name: Recherche Clinique Paris Descartes Necker Cochin Sainte Anne
name: Amiens University Hospital
name: University Hospital, Brest
name: Rennes University Hospital
name: Tenon Hospital, Paris
name: Centre Hospitalier Universitaire de Nice
name: University Hospital, Strasbourg, France
First posted: 2016-07-29
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Post-transplant diabetes affects 15 to 20% of renal transplant patients and contributes to increased morbidity and reduced survival of transplants and patients. Corticosteroids, anti-calcineurin and mammilian Target OF Rapamycin (mTOR) inhibitors have a major diabetogenic impact and greatly contribute to the increase in diabetes prevalence after transplantation.

There are to date few studies concerning the pharmacological prevention of post-transplant diabetes. Hecking et al. have recently reported that a short treatment with insulin, administered immediately after transplantation, reduce the incidence of de novo diabetes one-year post-transplant. This study included 50 renal transplant patients and showed that a three months treatment of (Neutral Protamine Hagedorn) NPH insulin decreased HbA1c. The occurrence of diabetes, a secondary end-point, was reduced by 73% in the treated group.

No further pharmacological strategy has been developed to date. Relevant experimental evidences suggest that gliptins could be used in the pharmacological prevention of post-transplant diabetes. These drugs are inhibitors of dipeptidyl peptidase-4 (DPP-4), which inactivates the incretins, the glucagon-like peptide-1 (GLP-1) and the gastric inhibitory polypeptide (GIP). DPP-4 inhibition causes an increase in the GLP-1 and GIP concentrations which induce insulin secretion and inhibition of glucagon secretion. The gliptins are approved for the treatment of type 2 diabetes. Beyond the effects on blood glucose, gliptins have pleiotropic effects including a protective effect on β cells and anti-inflammatory effect.

The additional cost associated with new-onset diabetes after transplantation could be also significantly reduced by efficient prevention. A US study found that, for the period between 1994 and 1998, a newly diagnosed diabetic patient has cost $21,500 of medical expenses 2 years after transplantation. Moreover, transplantation resulting in one of the best increases of patients' quality of life, its estimate is essential in the treatment evaluation of this population.


Eligibility criteria: Inclusion Criteria:

* Major Patients (18 year old or older)
* Signature of informed consent
* Affiliation to a French social security or receiving such a scheme
* Patient receiving a first kidney transplant
* Patients considered at high risk of developing posttransplant diabetes having at least 2 of the 3 following criteria: Age\> 50 years; BMI greater than 30 kg/m²; Direct Family history of type 2 diabetes
* Patients who can receive immunosuppressive therapy including tacrolimus, mycophenolic acid and steroids
* Patients in whom the cessation of steroids may be considered at the latest at Month 3 post-transplant

Exclusion Criteria:

* Legal disability or limited legal capacity
* Topic unlikely to cooperate in the study and / or low early cooperation by the investigator
* Patient without health insurance
* Pregnancy
* Patient in the period of exclusion of another study or under the "national register of volunteers."
* Inability to understand the reasons for the study; psychiatric disorders judged by the investigator to be incompatible with the inclusion in the study
* Active infection
* Infection with Hepatitis C virus
* A history of diabetes
* Multi-Organ Transplantation

Primary outcomes:
measure: Diabetes event
timeFrame: 1 year
Secondary outcomes:
measure: Glycemic control
timeFrame: 3, 6 and 12 months
measure: Acute rejection, infections, graft and patient survival
timeFrame: 3, 6 and 12 months
measure: The health-related quality of life improvement
timeFrame: 3, 6 and 12 months
measure: The cost-effectiveness ratio
timeFrame: 1 year
Other outcomes:
Locations:
city: Besançon
country: France
facility: CHU de Besançon
Study officials:
affiliation: Besançon University Hospital, Nephrology department
name: Didier Ducloux, Pr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gaiffe E, Crepin T, Bamoulid J, Courivaud C, Buchler M, Cassuto E, Albano L, Chemouny JM, Choukroun G, Hazzan M, Kessler L, Legendre C, Le Meur Y, Ouali N, Thierry A, Anota A, Nerich V, Limat S, Bonnetain F, Vernerey D, Ducloux D. 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 Jun 21;20(1):375. doi: 10.1186/s13063-019-3392-6.