VITamine D Supplementation in RenAL Transplant Recipients - VITALE

NCT ID: NCT01431430

Last Updated: 2025-09-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 538 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-06
• Study Completion Date: 2016-02-02

Brief Summary

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.

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).

Conditions

Renal Transplant Candidate for Right Kidney

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Cholecalciferol 100 000 UI

Cholecalciferol 100 000 UI FORTHIGHTLY for 2 months then monthly for 22 months

Group Type: EXPERIMENTAL

Cholecalciferol 100 000 UI

Intervention Type: DRUG

Cholecalciferol 100 000 UI FORTHIGHTLY for 2 months then monthly for 22 months

Cholecalciferol 12 000 UI (Control)

Cholecalciferol 12 000 UI FORTHIGHTLY for 2 months then monthly for 22 months.

Group Type: ACTIVE_COMPARATOR

Cholecalciferol 12 000 UI

Intervention Type: DRUG

Cholecalciferol 12 000 UI FORTHIGHTLY for 2 months then monthly for 22 months.

Interventions

Cholecalciferol 100 000 UI

Cholecalciferol 100 000 UI FORTHIGHTLY for 2 months then monthly for 22 months

Intervention Type: DRUG

Cholecalciferol 12 000 UI

Cholecalciferol 12 000 UI FORTHIGHTLY for 2 months then monthly for 22 months.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Laboratoire Crinex

UNKNOWN

Sponsor Role: collaborator

URC-CIC Paris Descartes Necker Cochin

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eric THERVET, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

European Georges Pompidou Hospital

Locations

Georges Pompidou European Hospital

Paris, , France

Countries

France

References

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.

Reference Type: BACKGROUND

PMID: 36695682 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25376735 (View on PubMed)

Other Identifiers

P100103

Identifier Type: -

Identifier Source: org_study_id