VITamine D Supplementation in RenAL Transplant Recipients - VITALE (VITALE)

Prospective Double Blind Multicentre Randomized Trial of Vitamine D Estimating the Profit of a Treatment by Vitamin D3 at the Dose of 100000 UI by Comparison With a Treatment in the Dose of 12 000 UI at Renal Transplanted Patients

It has been proposed that the intake of high dose of cholecalciferol may have beneficial non classical effects (beside bone health). This could include the reduction of type 2 diabetes mellitus, cardiovascular diseases, cancers, autoimmune and infectious diseases. These pleiotropic effects are mostly documented by observational and experimental studies or small intervention trials. In renal transplant recipients, vitamin D insufficiency, defined as circulating 25(OH)vitamin D (25OHD) less than 30 ng/mL, is a frequent finding and this population is at risk of the previously cited complications.The primary purpose of this study is to compare the effects of high dose vs. low dose of cholecalciferol on a composite endpoint consisting in de novo diabetes mellitus, cardiovascular diseases, de novo cancer and patient death.Renal transplant recipients between 12 and 48 months after transplantation will be randomized to blindly receive either high or low dose of cholecalciferol with a follow-up of 2 years.

Study Overview

• Status: Completed
• Conditions: Renal Transplant Candidate for Right Kidney
• Intervention / Treatment: Drug: Cholecalciferol 100 000 UI; Drug: Cholecalciferol 12 000 UI

Detailed Description

Rationale :

Vitamin D cannot be considered any more as only necessary to prevent rickets or osteomalacia. Calcitriol produced in the kidney is known to have classical endocrine PHOSPHOCALCIC properties. More recently, vitamin D has been shown to play an important role in reducing the risk of many chronic diseases including type 2 diabetes mellitus, cardiovascular diseases, cancers, autoimmune and infectious diseases. These effects may be secondary to local production of calcitriol and to its autocrine and paracrine actions on cellular proliferation and differentiation, apoptosis, insulin and renin secretion, interleukin and bactericidal proteins production. These pleiotropic effects are mostly documented by observational and experimental studies or small intervention trials that most often evaluated intermediate parameters. In renal transplant recipients, vitamin D insufficiency (circulating 25OHD<30 ng/mL or 75 nmol/L) , is a frequent finding with more than 80% of patients displaying this profile.

Objective:

Primary objective: compare the effects of high dose vs. low dose of cholecalciferol on a composite endpoint including

• De novo diabetes mellitus (fasting glycemia > 7 MMOLES/l or glycemia > 11 MMOLES/l)
• Cardiovascular complications (acute coronary heart disease, acute heart failure, lower-extremity arterial disease, cerebrovascular disease).
• De novo cancer,
• Patient death.

Secondary objectives : compare the effects of high dose vs. low dose of cholecalciferol on

• The occurrence of each event constituting the primary endpoint
• Blood pressure and blood pressure control (number and dosage of antihypertensive drugs)
• Echocardiography findings
• Infection including opportunistic (CMV, pneumocystis, nocardial infection, cryptococcal infection, aspergillosis)
• Acute rejection episode
• Renal allograft function including estimated glomerular filtration rate and proteinuria - Graft survival
• PHOSPHOCALCIC biological and clinical relevant parameters : Evolution of serum 25OHD, calcaemia, phosphataemia, serum PTH, bone mineral density and incidence of fractures
• Renal lithiasis

Study protocol

Number of patients: 320 patients in each group Inclusions : 2 years Follow-up after inclusion : 2 years Prospective, randomized, multicentre, double blind clinical study comparing high dose cholecalciferol [100 000 UI FORTHIGHTLY for 2 months then monthly for 22 months) vs. low dose cholecalciferol [12 000 UI FORTHIGHTLY for 2 months then monthly for 22 months).

• Study Type: Interventional
• Enrollment (Actual): 538
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Georges Pompidou European hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Renal transplant recipients between 12 and 48 months after transplantation with a stable renal function during the past 3 months.
• Vitamine D insufficiency defined as a concentration of 25OHD lower than 30 ng/ml.
• Patient between 18 and 75 years old
• Patient capable of understanding the advantages and the risks of the study.
• Affiliated with social security health insurance
• Written informed consent

Exclusion Criteria:

• Calcaemia > 2,7 mmol/l
• Phosphataemia > 1,5 mmol/l
• Serum creatinine > 250 µmol/l
• Treatment by an active form of the vitamin D not being able to be interrupted
• Transplant of an organ other than the kidney
• Type I or type II diabetes mellitus
• Past medical history of granulomatosis or active granulomatosis
• Primary hyperoxaluria
• Malabsorption proved by the liposoluble vitamins
• Simultaneous participation in another therapeutic essay
• Patients presenting a drug addiction or a psychiatric disorder
• Pregnant or breast-feeding women
• Vitamin D hyper sensibility

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cholecalciferol 100 000 UI; Cholecalciferol 100 000 UI FORTHIGHTLY for 2 months then monthly for 22 months	Drug: Cholecalciferol 100 000 UI; Cholecalciferol 100 000 UI FORTHIGHTLY for 2 months then monthly for 22 months
Active Comparator: Cholecalciferol 12 000 UI (Control); Cholecalciferol 12 000 UI FORTHIGHTLY for 2 months then monthly for 22 months.	Drug: Cholecalciferol 12 000 UI; Cholecalciferol 12 000 UI FORTHIGHTLY for 2 months then monthly for 22 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
De novo diabetes mellitus	De novo diabetes mellitus (fasting glycemia > 7 mmoles/l or glycemia > 11 mmoles/l)	2 years
Cardiovascular complications	Cardiovascular complications (acute coronary heart disease, acute heart failure, lower-extremity arterial disease, cerebrovascular disease).	2 years
De novo cancer	Diagnosis of the incidence of any new cancer	2 years
Patient death		2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure control	Blood pressure and blood pressure control (number and dosage of antihypertensive drugs)	2 years
Echocardiography findings	Comparison of left ventricular ejection fraction	2 years
Infection including opportunistic	Infection including opportunistic (CMV, pneumocystis, nocardial infection, cryptococcal infection, aspergillosis)	2 years
Acute rejection episode		2 years
Renal allograft function	Renal allograft function including estimated glomerular filtration rate, proteinuria	2 years
Graft survival		2 years
Phosphocalcic biological and clinical relevant parameters	PHOSPHOCALCIC biological and clinical relevant parameters : Evolution of serum 25OHD, calcaemia, phosphataemia, serum PTH, bone mineral density and incidence of fractures	2 years
Renal lithiasis		2 years

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Laboratoire Crinex; Unité de Recherche Clinique Necker Cochin, France
• Investigators: Principal Investigator: Eric THERVET, MD, PhD, European Georges Pompidou Hospital

Publications and helpful links

General Publications

• Courbebaisse M, Bourmaud A, Souberbielle JC, Sberro-Soussan R, Moal V, Le Meur Y, Kamar N, Albano L, Thierry A, Dantal J, Danthu C, Moreau K, Morelon E, Heng AE, Bertrand D, Arzouk N, Perrin P, Morin MP, Rieu P, Presne C, Grimbert P, Ducloux D, Buchler M, Le Quintrec M, Ouali N, Pernin V, Bouvier N, Durrbach A, Alamartine E, Randoux C, Besson V, Hazzan M, Pages J, Colas S, Piketty ML, Friedlander G, Prie D, Alberti C, Thervet E. Nonskeletal and skeletal effects of high doses versus low doses of vitamin D3 in renal transplant recipients: Results of the VITALE (VITamin D supplementation in renAL transplant recipients) study, a randomized clinical trial. Am J Transplant. 2023 Mar;23(3):366-376. doi: 10.1016/j.ajt.2022.12.007. Epub 2023 Jan 9.
• Courbebaisse M, Alberti C, Colas S, Prie D, Souberbielle JC, Treluyer JM, Thervet E. 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. Trials. 2014 Nov 6;15:430. doi: 10.1186/1745-6215-15-430.

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2012
• Primary Completion (Actual): February 2, 2016
• Study Completion (Actual): February 2, 2016

Study Registration Dates

• First Submitted: August 22, 2011
• First Submitted That Met QC Criteria: September 8, 2011
• First Posted (Estimated): September 9, 2011

Study Record Updates

• Last Update Posted (Estimated): September 8, 2025
• Last Update Submitted That Met QC Criteria: September 1, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: cancer; diabetes mellitus; renal transplantation; cardiovascular complications; Vitamine D
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Nutritional and Metabolic Diseases; Neoplasms; Diabetes Mellitus; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: P100103