VITamine D Supplementation in RenAL Transplant Recipients - VITALE
Condition: Renal Transplant Candidate for Right Kidney
Study type: Interventional
Phase: Phase 4

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).
    

Intervention name(s): Cholecalciferol 100 000 UI; Cholecalciferol 12 000 UI
Intervention type(s): Drug; Drug
Intervention description(s): Cholecalciferol 100 000 UI FORTHIGHTLY for 2 months then monthly for 22 months; Cholecalciferol 12 000 UI FORTHIGHTLY for 2 months then monthly for 22 months.
Intervention MeSH terms: Cholecalciferol; Vitamin D
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Vitamine D; renal transplantation; diabetes mellitus; cancer; cardiovascular complications