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Trial registered on ANZCTR


Trial ID
ACTRN12613001234707
Ethics application status
Approved
Date submitted
9/10/2013
Date registered
12/11/2013
Date last updated
30/04/2015
Type of registration
Retrospectively registered

Titles & IDs
Public title
A randomised controlled trial comparing daily (400 international units) and single bolus dosing (50,000 international units) of vitamin D in healthy breastfed infants of vitamin D deficient mothers.
Scientific title
A randomised controlled trial evaluating the efficacy and safety of single bolus (50,000 international units) versus daily (400 international units) dosing of vitamin D in healthy breastfed infants of vitamin D deficient mothers.
Secondary ID [1] 282609 0
nil
Secondary ID [2] 286616 0
The VINE study
Universal Trial Number (UTN)
Nil
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
vitamin D deficiency in healthy term babies born the mothers who are vitamin D deficient 289303 0
Condition category
Condition code
Metabolic and Endocrine 289636 289636 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
arm 1: 400IU vitamin D orally - Pentavite (Bayer Health) given daily for 4 months from birth
arm 2: 50,000 vitamin D orally - Given as pharmacy formulated Cholecalciferol as a single dose at birth only.
Patients will be followed up at 6-8 days of age and 3-4 months of age for biochemical markers of vitamin D deficiency (vitamin D and calcium levels) and reviewed for compliance, growth, side effects and signs of vitamin d deficiency
Intervention code [1] 287281 0
Treatment: Drugs
Comparator / control treatment
arm 1 = active standard treatment
400IU vitamin D given orally on a daily basis for 4 months
Control group
Active

Outcomes
Primary outcome [1] 289720 0
25 OH vitamin D levels. This will be assessed by immunoassay on a Liason analyser.
Timepoint [1] 289720 0
at birth using cord blood.
at 6-8 days using blood collected from patients
at 3-4 months using blood collected from patients
Secondary outcome [1] 303107 0
Total Calcium and albumin levels as a measure of safety of vitamin D supplementation. These parameters will be measured by routine laboratory methods on a Beckman auto analyser.
Timepoint [1] 303107 0
At birth
at 6-8 days
at 3-4 months
Secondary outcome [2] 305440 0
clinical parameters of vitamin D deficiency by assessment of growth parameters (head circumference, weight and length) and clinical signs of vitamin D deficiency such as craniotabes, widened anterior fontanelle, limb deformities, rachitic rosary.
Timepoint [2] 305440 0
At birth
at 6-8 days of age
at 3-4 months of age
Secondary outcome [3] 305441 0
measurement of compliance to vitamin D supplementation. This will be achieved by reconciling the remaining volumes of medication with expected volumes as recorded by the clinical trials pharmacy.
Timepoint [3] 305441 0
at 6-8 days
at 3-4 months on final review

Eligibility
Key inclusion criteria
term, singleton babies
mothers with vitamin D levels < 50 at > 35 week
intention to breastfeed
Minimum age
0 Hours
Maximum age
5 Months
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
intra-uterine growth restriction
pre-existing maternal diabetes, thyroid disorders
Neonates requiring significant resuscitation, CPR and intubation
maternal drug dependence
twin pregnancies

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)
antenatal screening for maternal vitamin D levels. consent and recruitment can be in antenatal clinic, birth suite, or pregnancy care centre/pregnancy day stay unit. Blinded randomisation to occur at birth from opaque sealed envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomisation using a schedule generated by computer software (i.e computer sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The sample size calculation was undertaken using the following assumptions: power = 90%; alpha = 0.05 (2-sided); 55% of patients in the control group (daily dosing vitamin D) having 25 OH vit D levels > 50nmol/L at 4 months of age; and 95% of patients in the intervention group (single bolus group) having 25 OH vit D levels > 50nmol/L at 4 months of age. Based on these parameters, 28 patients will be needed in each group. To allow for 20% drop-out, we will recruit an extra 4 patients in each.

The above presumption is based on published reports of 45% non compliance in the daily group and therefore presumed to have suboptimal vitamin D levels. This percentage is a realistic reflection of the high drop out rates and poor compliance seen in the multicultural population at Western Health services. Theoretically, 100% of patients in the intervention group would be expected to be vitamin D replete, however it is presumed for this study that 95% will be replete to account for a small population who may be poor metabolisers (absent or impaired 24 hydroxylase enzyme) of vitamin D.

Recruitment
Recruitment status
Completed
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)
VIC
Recruitment postcode(s) [1] 7418 0
3021 - St Albans

Funding & Sponsors
Funding source category [1] 288109 0
Hospital
Name [1] 288109 0
Department of Paediatrics, Sunshine Hospital
Address [1] 288109 0
176 Furlong Rd, St Albans 3021, Victoria
Country [1] 288109 0
Australia
Funding source category [2] 288241 0
Other Collaborative groups
Name [2] 288241 0
Australian Institute of Musculoskeletal Science
Address [2] 288241 0
Sunshine Hospital
Western Centre for Health and Research
176 Furlong Rd, St Albans 3021, Victoria
Country [2] 288241 0
Australia
Primary sponsor type
Hospital
Name
Sunshine Hospital
Address
176 Furlong Rd
St Albans 3021, Victoria
Country
Australia
Secondary sponsor category [1] 286829 0
Other Collaborative groups
Name [1] 286829 0
Australian Institute MusculoSkeletal Science (AIMSS)
Western Centre for Health and Research
Address [1] 286829 0
Sunshine Hospital
176 Furlong Rd
St Albans 3021, Victoria
Country [1] 286829 0
Australia
Other collaborator category [1] 277646 0
Individual
Name [1] 277646 0
Dr James Doery
Address [1] 277646 0
Monash Medical centre
246 Monash Rd, Clayton 3168 Victoria
Country [1] 277646 0
Australia
Other collaborator category [2] 277647 0
Individual
Name [2] 277647 0
Prof Danny Liew
Address [2] 277647 0
Melbourne Epicentre
University of Melbourne and Melbourne Health
Grattan St, Parkville, 3052 Victoria
Country [2] 277647 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290031 0
Royal Children Hospital
Ethics committee address [1] 290031 0
50 Flemington Rd
Parkville 3052, Victoria
Ethics committee country [1] 290031 0
Australia
Date submitted for ethics approval [1] 290031 0
08/04/2013
Approval date [1] 290031 0
28/05/2013
Ethics approval number [1] 290031 0
33044A

Summary
Brief summary
To assess the proportion of breastfed infants who are vitamin D sufficient (25 OH vit D > 50nmol/L) in the intervention group (bolus vitamin D dosing) versus the standard daily vitamin D dosing. This will be achieved by measurement of 25 OH vit D levels ; a marker of vitamin D status.
This is an open label, single site - hospital based centre
Primary: Proportion of subjects at 4 months of age with 25 OH vit D levels > 50nmol/L.
Secondary: Total calcium as marker of safety, compliance, clinical
markers of vitamin D deficiency
Recruitment period: May – Feb 2014. Four month follow up period
1) 400 IU vitamin D daily
2) 50,000 IU at birth only (bolus)
Sample size of 70 with 28 in each group + drop out rate.
Term breastfed infants born to pregnant women who are found to be vitamin D deficient (25 OH vit D < 50nmol/L) at 35-37 weeks gestation
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 40482 0
Dr Julie Huynh
Address 40482 0
Sunshine Hospital
176 Furlong Rd
St Albans 3021, Victoria
Country 40482 0
Australia
Phone 40482 0
+61 3 8345 1333
Fax 40482 0
Email 40482 0
julie.huynh@wh.org.au
Contact person for public queries
Name 40483 0
A/Prof Christine Rodda
Address 40483 0
Sunshine Hospital
University of Melbourne
North West Academic Centre
level 3, Rm 5.056
Sunshine Hospital
176 Furlong Rd, St Albans 3021, Victoria
Country 40483 0
Australia
Phone 40483 0
+61 3 8395 8161
Fax 40483 0
Email 40483 0
christine.rodda@unimelb.edu.au
Contact person for scientific queries
Name 40484 0
Dr Julie Huynh
Address 40484 0
Sunshine Hospital
176 Furlong Rd
St Albans 3021, Victoria
Country 40484 0
Australia
Phone 40484 0
+61 3 8345 1333
Fax 40484 0
Email 40484 0
julie.huynh@wh.org.au