Overview

This trial is active, not recruiting.

Condition renal transplant candidate for right kidney
Treatments cholecalciferol 100 000 ui, cholecalciferol 12 000 ui
Phase phase 4
Sponsor Assistance Publique - Hôpitaux de Paris
Collaborator Laboratoire Crinex
Start date January 2012
End date December 2016
Trial size 538 participants
Trial identifier NCT01431430, P100103

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
Cholecalciferol 100 000 UI FORTHIGHTLY for 2 months then monthly for 22 months
cholecalciferol 100 000 ui
Cholecalciferol 100 000 UI FORTHIGHTLY for 2 months then monthly for 22 months
(Active Comparator)
Cholecalciferol 12 000 UI FORTHIGHTLY for 2 months then monthly for 22 months.
cholecalciferol 12 000 ui
Cholecalciferol 12 000 UI FORTHIGHTLY for 2 months then monthly for 22 months.

Primary Outcomes

Measure
De novo diabetes mellitus
time frame: 2 years
Cardiovascular complications
time frame: 2 years
De novo cancer
time frame: 2 years
Patient death
time frame: 2 years

Secondary Outcomes

Measure
Blood pressure control
time frame: 2 years
Echocardiography findings
time frame: 2 years
Infection including opportunistic
time frame: 2 years
Acute rejection episode
time frame: 2 years
Renal allograft function
time frame: 2 years
Graft survival
time frame: 2 years
Phosphocalcic biological and clinical relevant parameters
time frame: 2 years
Renal lithiasis
time frame: 2 years

Eligibility Criteria

Male or female participants from 18 years up to 75 years old.

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

Additional Information

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
Principal investigator Eric THERVET, MD, PhD
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).
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by Assistance Publique - Hôpitaux de Paris.