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VITamine D Supplementation in RenAL Transplant Recipients - VITALE

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Laboratoire Crinex
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01431430
First received: August 22, 2011
Last updated: November 12, 2014
Last verified: November 2014
  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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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:


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

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 including opportunistic (CMV, pneumocystis, nocardial infection, cryptococcal 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 glomerular filtration rate, proteinuria

  • 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 ]

Enrollment: 538
Study Start Date: January 2012
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: December 2015 (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
Other Name: Cholecalciferol 100 000 UI
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.
Other Name: Cholecalciferol 12 000 UI

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
Genders Eligible for Study:   Both
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

No publications provided

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: November 12, 2014
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Vitamine D
renal transplantation
diabetes mellitus
cancer
cardiovascular complications

Additional relevant MeSH terms:
Cholecalciferol
Ergocalciferols
Vitamin D
Vitamins
Bone Density Conservation Agents
Growth Substances
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 27, 2014