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

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.

Conditions

• Disorder Related to Renal Transplantation
• Diabetes

Interventions

DRUG

Vildagliptin

Galvus is prescribed as recommended by the marketing authorization. In adults, the recommended dose of Galvus is 100 mg per day (one tablet in the morning and another in the evening). In patients with moderate or severe kidney problems, the recommended dose is 50 mg once daily (one tablet in the morning). Patients with creatinine clearance greater than 50 ml/min the vildalgliptin dose will be 100 mg/day. For those whose clearance is less than 50 ml/min, the daily dose is 50 mg. The creatinine clearance will be measured each week. The treatment duration will be 3 months, divided into 2 months of complete treatment and one month of cessation treatment with half dose of vildagliptin.

DRUG

Placebo

The placebo is the same as Galvus (packaging, shape, color, registration) but will contain only excipient. The given dose will also be identical.

Sponsors & Collaborators

• University Hospital, Tours

  collaborator OTHER

• University Hospital, Lille

  collaborator OTHER

• Recherche Clinique Paris Descartes Necker Cochin Sainte Anne

  collaborator OTHER

• Amiens University Hospital

  collaborator OTHER

• University Hospital, Brest

  collaborator OTHER

• Rennes University Hospital

  collaborator OTHER

• Tenon Hospital, Paris

  collaborator OTHER

• Centre Hospitalier Universitaire de Nice

  collaborator OTHER

• University Hospital, Strasbourg, France

  collaborator OTHER

• Centre Hospitalier Universitaire de Besancon

  lead OTHER

Principal Investigators

• Didier Ducloux, Pr. · Besançon University Hospital, Nephrology department

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

90 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-10-26

Primary Completion

2024-07-31

Completion

2024-12-31

Countries

• France

Study Locations