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

NCT ID: NCT02849899

Last Updated: 2022-08-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 186 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-26
• Study Completion Date: 2024-12-31

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.

Conditions

Disorder Related to Renal Transplantation; Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Vildagliptin

Intervention Type: DRUG

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.

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Galvus; Excipient

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Tours

OTHER

Sponsor Role: collaborator

University Hospital, Lille

OTHER

Sponsor Role: collaborator

Recherche Clinique Paris Descartes Necker Cochin Sainte Anne

OTHER

Sponsor Role: collaborator

Amiens University Hospital

OTHER

Sponsor Role: collaborator

University Hospital, Brest

OTHER

Sponsor Role: collaborator

Rennes University Hospital

OTHER

Sponsor Role: collaborator

Tenon Hospital, Paris

OTHER

Sponsor Role: collaborator

Centre Hospitalier Universitaire de Nice

OTHER

Sponsor Role: collaborator

University Hospital, Strasbourg, France

OTHER

Sponsor Role: collaborator

Centre Hospitalier Universitaire de Besancon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Didier Ducloux, Pr.

Role: PRINCIPAL_INVESTIGATOR

Besançon University Hospital, Nephrology department

Locations

CHU de Besançon

Besançon, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Emilie Gaiffe, Dr.

Role: CONTACT

egaiffe@chu-besancon.fr

0381218824 ext. +33

Ingrid Tissot

Role: CONTACT

itissot@chu-besancon.fr

0381218427 ext. +33

Facility Contacts

Didier Ducloux, Prof.

Role: primary

ddculoux@chu-besancon.fr

+33381218585

Emilie Gaiffe, Dr.

Role: backup

egaiffe@chu-besancon.fr

+33381218824

References

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.

Reference Type: DERIVED

PMID: 31227028 (View on PubMed)

Other Identifiers

N/2015/70

Identifier Type: -

Identifier Source: org_study_id