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Trial registered on ANZCTR


Registration number
ACTRN12611001113943
Ethics application status
Approved
Date submitted
25/10/2011
Date registered
25/10/2011
Date last updated
26/10/2011
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of vitamin D replacement in patients with chronic kidney disease
Scientific title
Randomised controlled trial to determine the effect of vitamin D replacement on arterial stiffness and cardiometabolic risk factors in vitamin D deficient stage 3-5 chronic kidney disease patients
Secondary ID [1] 273264 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Vitamin D deficient stage 3-5 chronic kidney disease, with and without diabetes and pre dialysis 279030 0
Condition category
Condition code
Renal and Urogenital 279215 279215 0 0
Kidney disease
Diet and Nutrition 279216 279216 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Group 1: 1 tablet is equivalent to 50,000U of cholecalciferol (Vitamin D3). Participants will be required to take 2 oral tablets at randomisation, then 1 oral tablet monthly for 6 months (24 weeks). Participants may be required to increase their dose to one tablet fortnightly between 3- 6 months if their 25OH-VitD blood level is less than 50 nmol/L at 3 months (12 weeks).
Group 2 Placebo. The participants will be required to take the same number of oral placebo tablets as group one.
Intervention code [1] 269606 0
Treatment: Drugs
Comparator / control treatment
One placebo tablet contains lactose monohydrate NF (spray-dried).
Control group
Placebo

Outcomes
Primary outcome [1] 279849 0
To assess the effects of cholecalciferol at an initial dose of 100,000U then 50,000U monthly, or matched placebo, for 6 months on arterial stiffness in 25OHD deficient stage 3-5 CKD patients. Cardiovascular risk will be assessed at baseline (week 0) and 6 months (week 24) after starting study medication. Measurements with SphygmoCor system will include:
1. Augmentation index (Alx)
2. Pulse Wave Velocity (PWV)
Timepoint [1] 279849 0
Measured at baseline (week 0) prior to first dose of cholecalciferol and after 6 months (week 24) treatment
Secondary outcome [1] 294571 0
Inflammatory markers including interleukins 6, 12 and 18 and C-reactive protein
Timepoint [1] 294571 0
Measured at baseline (week 0) prior to first dose of cholecalciferol and after 6 months (week 24) treatment
Secondary outcome [2] 294572 0
Markers of insulin resistance including HOMA score and waist-hip circumference
Timepoint [2] 294572 0
Measured at baseline (week 0) prior to first dose of cholecalciferol and after 6 months (week 24) treatment
Secondary outcome [3] 294573 0
Lipid profile
Timepoint [3] 294573 0
Measured at baseline (week 0) prior to first dose of cholecalciferol and after 6 months (week 24) treatment
Secondary outcome [4] 294574 0
Markers of bone metabolism
Timepoint [4] 294574 0
Measured at baseline (week 0) prior to first dose of cholecalciferol and after 6 months (week 24) treatment
Secondary outcome [5] 294575 0
Change in kidney function (estimated glomerular filtration rate)
Timepoint [5] 294575 0
Measured at baseline (week 0) prior to first dose of cholecalciferol and after 6 months (week 24) treatment
Secondary outcome [6] 294576 0
Change in urine proteinuria (determined by spot urine protein/creatinine ratio)
Timepoint [6] 294576 0
Measured at baseline (week 0) prior to first dose of cholecalciferol and after 6 months (week 24) treatment

Eligibility
Key inclusion criteria
1. ages 18-80 years
2. Vitamin D deficiency (25OHD 15- 75nmol/L)
3. Stage 3-5 CKD, not yet on dialysis (eGFRof < 60mL/min/m2)
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1.Serum Calcium > 2.55mmol/L and/ or Phosphate > 1.80mmol/L
2. Severe Calcium deficiency (<15nmol/L)
3. Liver enzymes (Bilirubin, alanine aminotransferase, GGT) > 3 times upper limit of normal
4. Cardiovascular event or unstable cardiovascular disease in preceding 6 months 6 or NYHA heart failure stage III or IV
5. Significant psychiatric disorder
6. Active infection or inflammation
7. Pregnancy/ planning pregnancy
8. Significant proteinuria (= to > 3g/d)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Randomization will be performed by an authorized person not directly involved in the trial. This authorized person will receive a set of treatment allocation cards with sequential randomization numbers on which the treatment group information is covered by a peel-off label.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The treatment allocation cards are used to avoid bias in the assignment of the patients to Group 1 and Group 2 in the specified 1:1 ratio by a simple randomisation technique similar to coin-tossing. For diabetic patients, a separate treatment allocation cards with sequential randomization numbers on which the treatment group information is covered by a peel-off label will be provided. Diabetic patients will be stratified to both groups in a sequential manner to ensure similar proportion of high-risk patients in both groups.
.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 284094 0
Hospital
Name [1] 284094 0
Sir Charles Gairdner Hospital, Research Advisory Committee
Address [1] 284094 0
Hospital Ave.
Nedlands, Western Australia, 6009
Country [1] 284094 0
Australia
Funding source category [2] 284095 0
Hospital
Name [2] 284095 0
Department of Renal Medicine, Sir Charles Gairdner Hospital
Address [2] 284095 0
Hospital Ave.
Nedlands, Western Australia, 6009
Country [2] 284095 0
Australia
Primary sponsor type
Hospital
Name
Sir Charles Gairdner Hospital Group
Address
Hospital Ave.
Nedlands, Western Australia, 6009
Country
Australia
Secondary sponsor category [1] 269057 0
None
Name [1] 269057 0
Address [1] 269057 0
Country [1] 269057 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 272044 0
Sir Charles Gairdner Hospital
Ethics committee address [1] 272044 0
Hospital Ave.
Nedlands, Western Australia 6009
Ethics committee country [1] 272044 0
Australia
Date submitted for ethics approval [1] 272044 0
01/10/2010
Approval date [1] 272044 0
07/04/2011
Ethics approval number [1] 272044 0
2010-099

Summary
Brief summary
Vitamin D deficiency is common in patients with chronic kidney disease and has been associated with increased risk of heart disease and death. Correcting vitamin D deficiency may improve risk for heart disease through its effects on blood vessel, immune and bone cell function. Stiffness of the arteries (arterial stiffness) is associated with increased risk of heart disease and can be measured using simple non-invasive methods. The effect of vitamin D replacement on arterial stiffness has not previously been studied in patients with kidney disease.
This study will examine the effect of vitamin D, a commonly used over-the-counter medication, compared with placebo (“dummy tablet”) on blood vessel function in people with moderate to severe chronic kidney disease who are vitamin D deficient. In this study, you will be randomly assigned (”like flipping a coin”) to take either vitamin D or placebo (1 tablet monthly) for 6 months. If at 3 months, your vitamin D levels remain low, you may need to take the study medications every 2 weeks till the end of the study.
Both the vitamin D and placebo medication will be supplied by a specialist compounding pharmacy with a state of the art compounding laboratory and is accredited by the Pharmacy Guild of Australia as a quality care pharmacy and as such operates under a quality care program.
If you enter the full study, you will have blood tests and blood vessel function studies before you start and after you complete the study medication. During the study, you will not know which treatment you are on. Your other medications will remain constant. The study requires you to attend the Research Unit at Sir Charles Gairdner Hospital 4 times over a 6-month period.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33304 0
Address 33304 0
Country 33304 0
Phone 33304 0
Fax 33304 0
Email 33304 0
Contact person for public queries
Name 16551 0
Dr Wai Lim
Address 16551 0
Department of Renal Medicine
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands, western Australia, 6009
Country 16551 0
Australia
Phone 16551 0
+61 8 9346 2799
Fax 16551 0
+61 8 9346 3942
Email 16551 0
Wai.Lim@health.wa.gov.au
Contact person for scientific queries
Name 7479 0
Dr. wai lim
Address 7479 0
Department of Renal Medicine
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands, western Australia, 6009
Country 7479 0
Australia
Phone 7479 0
+61 8 9346 2799
Fax 7479 0
+61 8 9346 3942
Email 7479 0
Wai.Lim@health.wa.gov.au

No data has been provided for results reporting
Summary results
Not applicable