VITamin D supplementation in renAL transplant recipients (VITALE): a prospective, multicentre, double-blind, randomized trial of vitamin D estimating the benefit and safety of vitamin D3 treatment at a dose of 100,000 UI compared with a dose of 12,000 UI in renal transplant recipients: study protocol for a double-blind, randomized, controlled trial

Marie Courbebaisse, Corinne Alberti, Sandra Colas, Dominique Prié, Jean-Claude Souberbielle, Jean-Marc Treluyer, Eric Thervet, Marie Courbebaisse, Corinne Alberti, Sandra Colas, Dominique Prié, Jean-Claude Souberbielle, Jean-Marc Treluyer, Eric Thervet

Abstract

Background: In addition to their effects on bone health, high doses of cholecalciferol may have beneficial non-classic effects including the reduction of incidence of type 2 diabetes mellitus, cardiovascular disease, and cancer. These pleiotropic effects have been documented in observational and experimental studies or in small intervention trials. Vitamin D insufficiency is a frequent finding in renal transplant recipients (RTRs), and this population is at risk of the previously cited complications.

Methods/design: The VITALE study is a prospective, multicentre, double-blind, randomized, controlled trial with two parallel groups that will include a total of 640 RTRs. RTRs with vitamin D insufficiency, defined as circulating 25-hydroxyvitamin D levels of less than 30 ng/ml (or 75 nmol/l), will be randomized between 12 and 48 months after transplantation to blinded groups to receive vitamin D3 (cholecalciferol) either at high or low dose (respectively, 100,000 UI or 12,000 UI every 2 weeks for 2 months then monthly for 22 months) with a follow-up of 2 years. The primary objective of the study is to evaluate the benefit/risk ratio of high-dose versus low-dose cholecalciferol on a composite endpoint consisting of de novo diabetes mellitus; major cardiovascular events; de novo cancer; and patient death. Secondary endpoints will include blood pressure (BP) control; echocardiography findings; the incidences of infection and acute rejection episodes; renal allograft function using estimated glomerular filtration rate; proteinuria; graft survival; bone mineral density; the incidence of fractures; and biological relevant parameters of mineral metabolism.

Discussion: We previously reported that the intensive cholecalciferol treatment (100 000 IU every 2 weeks for 2 months) was safe in RTR. Using a pharmacokinetic approach, we showed that cholecalciferol 100,000 IU monthly should maintain serum 25-hydroxyvitamin D at above 30 ng/ml but below 80 ng/ml after renal transplantation. Taken together, these results are reassuring regarding the safety of the cholecalciferol doses that will be used in the VITALE study. Analysis of data collected during the VITALE study will demonstrate whether high or low-dose cholecalciferol is beneficial in RTRs with vitamin D insufficiency.

Trial registration: ClinicalTrials.gov Identifier: NCT01431430.

Figures

Figure 1
Figure 1
Flowchart of the VITALE study. RTR with 25OHD insufficiency (25OHD <30 ng/ml) will be included 12 to 48 months after renal transplantation in 30 transplantation departments in France, and randomized to receive either high-dose cholecalciferol treatment (100,000 IU every other week, equivalent to 6,600 IU daily for 2 months, then 100,000 IU monthly, equivalent to 3,300 IU daily for 22 months) or low-dose cholecalciferol treatment (12,000 IU every other week, equivalent to 800 IU daily for 2 months, then 12,000 IU monthly, equivalent to 400 IU daily for 22 months, which is the French recommended dietary intake). Duration of patient follow-up will be 2 years. VITALE is a double-blind study as a single-dose vial of 100,000 or 12,000 IU have exactly the same appearance. We aim to include 320 RTR sin each group (high-dose group and low-dose group) over a period of approximately 2 years. Statistical analysis will be performed at the end of the study.

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