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

Prevention of New Onset Diabetes After Transplantation by a Short Term Treatment of Vildagliptin in the Early Post-transplant Period

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.

Study Overview

• Status: Recruiting
• Conditions: Diabetes; Disorder Related to Renal Transplantation
• Intervention / Treatment: Drug: Vildagliptin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 186
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Emilie Gaiffe, Dr.; Phone Number: +33 0381218824; Email: egaiffe@chu-besancon.fr
• Study Contact Backup: Name: Ingrid Tissot; Phone Number: +33 0381218427; Email: itissot@chu-besancon.fr

Study Locations

• France
  • Besançon, France, 25000
    • Recruiting
    • CHU de Besancon
    • Contact: Didier Ducloux, Prof.; Phone Number: +33381218585; Email: ddculoux@chu-besancon.fr
    • Contact: Emilie Gaiffe, Dr.; Phone Number: +33381218824; Email: egaiffe@chu-besancon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	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.; Other Names: Galvus
Placebo Comparator: Placebo; Group 2 will be treated with placebo according to the same dosage.	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.; Other Names: Excipient

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diabetes event	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)	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycemic control	The criteria for secondary assessments are abnormal blood glucose measured by: the glycated hemoglobin (HbA1c) 3 months, 6 months and 12 months after transplantation.	3, 6 and 12 months
Acute rejection, infections, graft and patient survival	The occurrence of acute rejection, infection, graft loss and patient death 3 months, 6 months and 12 months after transplantation.	3, 6 and 12 months
The health-related quality of life improvement	The health-related quality of life (ReTRANSQOL questionnaire), 3 months, 6 months and 12 months after transplantation.	3, 6 and 12 months
The cost-effectiveness ratio	The cost-effectiveness of prevention of diabetes with vildagliptin	1 year

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Besancon
• Collaborators: University Hospital, Strasbourg, France; Centre Hospitalier Universitaire de Nice; University Hospital, Brest; Rennes University Hospital; University Hospital, Lille; University Hospital, Tours; Amiens University Hospital; Tenon Hospital, Paris; Recherche Clinique Paris Descartes Necker Cochin Sainte Anne
• Investigators: Principal Investigator: Didier Ducloux, Pr., Besançon University Hospital, Nephrology Department

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2018
• Primary Completion (Anticipated): July 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: July 19, 2016
• First Submitted That Met QC Criteria: July 26, 2016
• First Posted (Estimate): July 29, 2016

Study Record Updates

• Last Update Posted (Actual): August 2, 2022
• Last Update Submitted That Met QC Criteria: August 1, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Vildagliptin
• Other Study ID Numbers: N/2015/70

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No