VITamine D Supplementation in RenAL Transplant Recipients - VITALE - Full Text View

Purpose

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.

Condition	Intervention	Phase
Renal Transplant Candidate for Right Kidney	Drug: Cholecalciferol 100 000 UI Drug: Cholecalciferol 12 000 UI	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Participant, Investigator) Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Kidney Transplantation Vitamin D

Drug Information available for: Cholecalciferol Vitamin D

U.S. FDA Resources

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:

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

Secondary Outcome Measures:

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


Enrollment:	538
Study Start Date:	January 2012
Estimated Study Completion Date:	June 2017
Estimated Primary Completion Date:	December 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

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).

Eligibility


Ages Eligible for Study:	18 Years to 75 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01431430

Locations


France
Georges Pompidou European Hospital
Paris, France, 75015

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Laboratoire Crinex

Investigators


Principal Investigator:	Eric THERVET, MD, PhD	European Georges Pompidou Hospital

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Courbebaisse M, Alberti C, Colas S, Prié 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.


Responsible Party:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT01431430 History of Changes
Other Study ID Numbers:	P100103
Study First Received:	August 22, 2011
Last Updated:	August 25, 2016

Keywords provided by Assistance Publique - Hôpitaux de Paris:


Vitamine D renal transplantation diabetes mellitus cancer cardiovascular complications

Additional relevant MeSH terms:


Vitamins Vitamin D Ergocalciferols Cholecalciferol	Micronutrients Growth Substances Physiological Effects of Drugs Bone Density Conservation Agents

ClinicalTrials.gov processed this record on May 23, 2017

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