Prevention of Diabetes After Transplantation by Vildagliptin in the Early Post-transplant Period (PRODIG)

Centre Hospitalier Universitaire de Besancon

Status and phase: Enrolling; Phase 3

Conditions: Diabetes; Disorder Related to Renal Transplantation

Treatments: Drug: Vildagliptin; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02849899

N/2015/70

Details and patient eligibility

About

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.

Enrollment: 186 estimated patients

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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186 participants in 2 patient groups, including a placebo group

Vildagliptin

Active Comparator group

Description:

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.

Treatment:

Drug: Vildagliptin

Placebo

Placebo Comparator group

Description:

Group 2 will be treated with placebo according to the same dosage.

Treatment:

Drug: Placebo