VITamine D Supplementation in RenAL Transplant Recipients - VITALE

Renal Transplant Candidate for Right Kidney Clinical Trial

— VITALE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01431430
• Other study ID #: P100103
• Status: Completed
• Phase: Phase 4
• First received: August 22, 2011
• Last updated: December 20, 2017
• Start date: January 6, 2012
• Est. completion date: February 2, 2016

Study information

• Verified date: December 2017
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 538
• Est. completion date: February 2, 2016
• Est. primary completion date: February 2, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Renal Transplant Candidate for Right Kidney

Intervention

Drug:
• Cholecalciferol 100 000 UI
Cholecalciferol 100 000 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.

Locations

Country	Name	City	State
France	Georges Pompidou European Hospital	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Laboratoire Crinex

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	De novo diabetes mellitus	De novo diabetes mellitus (fasting glycemia > 7 mmoles/l or glycemia > 11 mmoles/l)	2 years
Primary	Cardiovascular complications	Cardiovascular complications (acute coronary heart disease, acute heart failure, lower-extremity arterial disease, cerebrovascular disease).	2 years
Primary	De novo cancer	Diagnosis of the incidence of any new cancer	2 years
Primary	Patient death		2 years
Secondary	Blood pressure control	Blood pressure and blood pressure control (number and dosage of antihypertensive drugs)	2 years
Secondary	Echocardiography findings	Comparison of left ventricular ejection fraction	2 years
Secondary	Infection including opportunistic	Infection including opportunistic (CMV, pneumocystis, nocardial infection, cryptococcal infection, aspergillosis)	2 years
Secondary	Acute rejection episode		2 years
Secondary	Renal allograft function	Renal allograft function including estimated glomerular filtration rate, proteinuria	2 years
Secondary	Graft survival		2 years
Secondary	Phosphocalcic biological and clinical relevant parameters	PHOSPHOCALCIC biological and clinical relevant parameters : Evolution of serum 25OHD, calcaemia, phosphataemia, serum PTH, bone mineral density and incidence of fractures	2 years
Secondary	Renal lithiasis		2 years