Prevention of Diabetes After Transplantation by Vildagliptin in the Early Post-transplant Period
- Conditions
- DiabetesDisorder Related to Renal Transplantation
- Interventions
- Drug: Placebo
- Registration Number
- NCT02849899
- Lead Sponsor
- Centre Hospitalier Universitaire de Besancon
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 186
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Group 2 will be treated with placebo according to the same dosage. Vildagliptin Vildagliptin Group 1 will be treated with Vildagliptin 50 or 100 mg/day for 2 months, then 25 or 50 mg/d for 1 month depending on their creatinine assay.
- Primary Outcome Measures
Name Time Method Diabetes event 1 year The primary endpoint is the proportion of diabetic patients 1 year after transplantation.
Diabetic patients are defined as one of the following proposals:
* Patients receiving a diabetic treatment
* Patients have a fasting glucose above 7 mmol/l
* Patients with an abnormal oral glucose tolerance test (OGTT)
- Secondary Outcome Measures
Name Time Method The health-related quality of life improvement 3, 6 and 12 months The health-related quality of life (ReTRANSQOL questionnaire), 3 months, 6 months and 12 months after transplantation.
Glycemic control 3, 6 and 12 months The criteria for secondary assessments are abnormal blood glucose measured by: the glycated hemoglobin (HbA1c) 3 months, 6 months and 12 months after transplantation.
The cost-effectiveness ratio 1 year The cost-effectiveness of prevention of diabetes with vildagliptin
Acute rejection, infections, graft and patient survival 3, 6 and 12 months The occurrence of acute rejection, infection, graft loss and patient death 3 months, 6 months and 12 months after transplantation.
Trial Locations
- Locations (1)
CHU de Besançon
🇫🇷Besançon, France