ISRCTN - ISRCTN82927713: Maternal vItamin D osteoporosis study

Plain English Summary

Background and study aims
Vitamin D is essential for the maintenance of strong bones. It is made in the skin through the action of sunshine with very little coming from the diet. In previous studies we have found that mothers who have low levels of vitamin D in pregnancy have children born with reduced bone mass and who have weaker bones when they are older. Given that low levels of vitamin D are relatively common in the population, we are now aiming to see whether supplementing women with vitamin D during pregnancy will lead to an improvement in the bone growth of the child whilst in the womb.

Who can participate?
We are enrolling women who come to the local maternity hospital for the initial dating or screening ultrasound scan at around 11 weeks pregnancy. Most women who are 18 years or older and are only carrying one baby are eligible; those who already have bone conditions or other serious illnesses are not appropriate for the study.

What does the study involve?
The women receive information about the study with their appointment for the ultrasound scan and a research nurse approaches them after they have had the scan to see if they would like to take part in the study. If they do, then a blood sample is taken to check their vitamin D level. If this comes back in the low-normal range, they return at 14 weeks pregnancy for an assessment of diet, lifestyle, body build and for a further reference vitamin D blood test. At this point they are randomly allocated to receive either vitamin D supplements (1,000 units daily) or a matched dummy (placebo/control) tablet. Neither they nor the research staff or study leaders know which they are taking. This treatment is continued for the duration of pregnancy until the baby is delivered. The women undergo a further ultrasound scan at 19 weeks as they would on the National Health Service (NHS) system, and are assessed again at 34 weeks with a repeat of the 14-week visit. When the baby is delivered, the attending midwives let the study team know and the baby has body measurements before it leaves hospital. We also collect blood from the umbilical cord. The babys bone size and density are measured using a DXA scan (a type of scanner that is used to assess older people for osteoporosis). We then follow up with the children at a yearly visit for body measurements and assessment of health and then at four years, a repeat bone density scan.

What are the possible benefits and risks of participating?
There are unlikely to be any side effects from this dose of vitamin D and participants, depending on the study centre, may benefit from their antenatal visits being in dedicated research centres.

Where is the study run from?
Southampton and other recruitment centres are in Sheffield and Oxford (UK).

When is the study starting and how long is it expected to run for?
The study commenced in September 2008 and the last participant is expected to be recruited during the latter part of 2012.

Who is funding the study?
Arthritis Research UK, Medical Research Council and BUPA Foundation.

Who is the main contact?
Dr Nicholas Harvey
nch@mrc.soton.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Prof Cyrus Cooper

ORCID ID

Contact details

Medical Research Council Epidemiology Resource Centre
Southampton General Hospital
Southampton
SO16 6YD
United Kingdom
+44 (0)23 8077 7624
cc@mrc.soton.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

1.5; 001-0002

Study information

Scientific title

A randomised double-blind placebo-controlled trial of vitamin D supplements for pregnant women with low levels of vitamin D in early pregnancy

Acronym

MAVIDOS

Study hypothesis

To test the hypothesis that vitamin D supplementation during pregnancy of women who have low levels of vitamin D will result in improved neonatal bone mineral content.

This trial is carried out by the MRC Epidemiology Resource Centre (http://www.mrc.soton.ac.uk).

Ethics approval

Southampton and Southwest Hampshire Research Ethics Committee, 03/12/2007, ref: 07/H0502/113

Study design

Multi-centre randomised double-blind placebo-controlled trial in two phases (pilot and main studies)

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Prevention

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Osteoporosis

Intervention

This trial comprises pilot and main studies:

Pilot study for the first 18 months, three groups of 60 participants each (total number of participants = 180):
Group 1: 400 iu vitamin D3 (oral) per day, from 14 weeks gestation to delivery
Group 2: 1,000 iu vitamin D3 (oral) per day, from 14 weeks gestation to delivery
Group 3: Placebo, from 14 weeks gestation to delivery

Main study will be vitamin D3 (dose chosen from pilot), from 14 weeks gestation to delivery vs placebo. 954 participants will be included in the main trial, 477 participants in each of the two arms (total number of participants = 954). The participants in the main trial vitamin D3 arm will include those who have participated in the pilot phase of the trial at the dose to be used in the main study i.e. 60 participants in the pilot study (either the 400 iu vitamin D3 or 1,000 iu vitamin D3 arm) will be included in the main study, and 894 new participants (954 - 60) will be recruited specifically for the main trial.

Intervention type

Supplement

Phase

Not Specified

Drug names

Vitamin D

Primary outcome measure

Neonatal whole body bone area, bone mineral content and bone mineral density assessed by dual energy x-ray absorptiometry (DXA) within 10 days of birth.

Secondary outcome measures

1. Neonatal and childhood anthropometry and body composition (weight, length and skinfold thickness measurements), assessed within 48 hours of birth
2. Women's attitude to pregnancy vitamin D supplementation (qualitative study; assessed in main study only). Methodology and timepoints of assessment not yet defined as of 03/03/2008
3. Childhood bone mass at 4 years

Overall trial start date

01/05/2008

Overall trial end date

01/12/2016

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Less than 19 weeks gestation at first assessment (based on last menstrual period [LMP] and dating scan)
2. Serum 25(OH)-vitamin D concentration is 25-100 nmol/l at nuchal fold/ dating scan (10 to 19 weeks gestation)
3. Aged over 18 years
4. Singleton pregnancy
5. Aiming to give birth at local hospital

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

1,074

Participant exclusion criteria

1. Known metabolic bone disease
2. Current medication likely to interfere with intrauterine growth (corticosteroids, anticonvulsants, parathyroid hormone [PTH], bisphosphonates)
3. Foetal physical anomalies on the 12 week scan
4. Inability to provide informed consent or comply with trial protocol
5. History of renal stones, hyperparathyroidism, hypercalcuria
6. Measured hypercalacemia (>2.75 mmol/l)
7. A diagnosis of cancer in the last 10 years
8. Cod liver oil of vitamin supplements containing vitamin D >200 iu per day
9. In-vitro fertilisation treatment

Recruitment start date

01/05/2008

Recruitment end date

01/12/2012

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Southampton General Hospital
Southampton
SO16 6YD
United Kingdom

Sponsor information

Organisation

Southampton University Hospitals NHS Trust (UK)

Sponsor type

Government

Website

http://www.suht.nhs.uk

Funders

Funder type

Charity

Funder name

Arthritis Research Campaign (ref: 17702) (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data