VITamine D Supplementation in RenAL Transplant Recipients - VITALE

• De novo diabetes mellitus [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  De novo diabetes mellitus (fasting glycemia > 7 mmoles/l or glycemia > 11 mmoles/l)
  
  
• Cardiovascular complications [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  Cardiovascular complications (acute coronary heart disease, acute heart failure, lower-extremity arterial disease, cerebrovascular disease).
  
  
• De novo cancer [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  Diagnosis of the incidence of any new cancer
  
  
• Patient death [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  

• Blood pressure control [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  Blood pressure and blood pressure control (number and dosage of antihypertensive drugs)
  
  
• Echocardiography findings [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  Comparison of left ventricular ejection fraction
  
  
• Infection including opportunistic [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  Infection inclunding opportunistic (CMV, pneumocystis, nocardial infection, crypotococcal infection, aspergillosis)
  
  
• Acute rejection episode [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  
• Renal allograft function [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  Renal allograft function including estimated glomurular filtration rate, proterinuria
  
  
• Graft survival [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  
• Phosphocalcic biological and clinical relevant parameters [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  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 ] [ Designated as safety issue: Yes ]
  

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

• 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 : 1 year 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).