Vitamin D And Lifestyle Intervention for Gestational Diabetes Mellitus (GDM) Prevention - A European multicentre, randomised trial: Vitamin D limb.

Gestational Diabetes (GDM) is defined as 'carbohydrate intolerance resulting in
hyperglycaemia of variable severity with onset or first recognition during
pregnancy'. The prevalence of GDM in Europe is reported to vary considerably,
in some populations GDM occurs already in up to 20 % of all pregnancies. There
are few published studies about preventing GDM.

The overall aim of the DALI study is to identify the best available measures to
prevent GDM in an ongoing pregnancy, to provide a cost-benefit calculation of
GDM prevention for health care systems, and to establish a pan-European cohort
of mother-offspring pairs for future analyses with a central biobank and data
base. For this purpose, a randomised controlled trial will be conducted in 10
European countries.

This is a multicentre, randomised trial across 10 European countries.

In this main trial, 880 participants will be randomised.

In essence the study consists of two trials conducted in parallel:

Trial 1:
1) counseling healthy diet
2) counseling physical activity
3) counseling physical activity & healthy diet
4) control group

Trial 2:
5) counseling physical activity & healthy diet & placebo
6) vitamin D (1600 IU/day)
7) counseling physical activity & healthy diet & vitamin D (1600 IU/day)
8) placebo.


1) physical activity, diet and physical activity and diet) or a control group.
The trial will be conducted in 10 European countries and in each country 44
women, without GDM, will be recruited (total n = 440) before 20 weeks of
pregnancy.

In the programme, one-to-one contact will be offered, along with telephone
booster calls. The same amount of time will be offered to each participant
during the trial. The intervention will be provided in five sessions of
approximately 30-45 minutes, and in four telephone calls of approximately 20
minutes. The on-to-one sessions will take place at the home of the participants
or in hospital/midwife practice/general practice, depending on cultural
acceptability of home visits. To optimize rapport, it is expected that a
lifestyle coach is made responsible for supporting a defined number of
participants throughout the pregnancy period. The coach will have a PDA which
will provide the framework for the visit and will help steer the coach to
deliver the nutrition and/or physical activity package. Details will be entered
into the PDA programme and at the end of the session, the synchronization
button will be pressed to send the recorded data to the Trial coordination team.

* Physical activity
According to the ACOG guidelines, pregnant women are recommended to be
moderately physically active for at least 30 minutes per day on at least 5 days
of the week [13]. Given our population of obese women, low fitness and physical
activity levels are to be expected. Activities such as swimming, walking and
cycling are activities that the participants should be able to undertake during
the course of their pregnancy. As pregnancy progresses through the third
trimester, physical activity may decrease and this needs to be managed
sympathetically, providing e.g. sitting and/or upper limb exercises as
alternatives. They are advised to (1) incorporate active movement as much as
possible into their daily life
(e.g. by parking further away from destination), (2) reduce sedentary time, (3)
incorporate upper and or lower limb resistance exercise as physical activity,
(4) to increase the number of steps taken per day and (5) to be more active
during the weekends. An action plan for increasing physical activity levels
will be made during the first session, and evaluated in subsequent sessions.
Participants will receive pedometers for feedback on their behaviour and
progress.

* Diet
The following dietary objectives will be set for each participant to achieve or
to maintain: (1) to reduce intake of sugary drinks (replace with water), (2) to
eat more non-starchy vegetables, (3) to choose high-fibre, over low fibre
products (*5 g fibre/100 g), (4) to watch portion size, (5) to increase intake
of proteins (e.g. meat, fish, beans), (6) to reduce fat intake (e.g. snack,
candy, fast food, fried foods), and (7) to reduce intake of carbohydrates (e.g.
potatoes, pasta, rice, snacks, candy) . An action plan for improving dietary
behaviour will be made during the first session, and evaluated in subsequent
sessions.

Coaches
Members of the research team will carry out the face-to-face counselling and
the telephone booster sessions. They will receive a special training programme
containing motivational interviewing techniques to overcome the ambivalence or
barriers that keeps people from making desired lifestyle changes in their
lives.

Risks and burden to the participant:
* Clinical assessments
There are 4 study assessment visits over 6-7 months. The assessments consist
of: urine samples, blood samples (including OGTT), ultrasound, body weight
measurement, and filling out questionnaires. Height will be measured at
baseline.
Most assessments can be performed shortly after a routine appointment to the
obstetrician / midwife, removing the need to have study-specific hospital
visits. The measurements will add approximately 30 minutes to a routine
appointment. The OGTT will take 2.5 hours. Venepuncture has a risk of bruising
and discomfort, but there is no risk of serious harm.

* Interventions
Women will be asked to take a daily dose of 1600 IU vitamin D supplementation,
which will not be a burden for the participants.

Potential risks of Vitamin D supplementation:
Vitamin D supplementation can potentially entail the risk of intoxication which
would be a serious complication that is virtually impossible at the doses
tested. Other potential risks are maternal hypercalciuria/nephrolithiasis and
allergy/asthma in the infant; they also seem unlikely at the doses used. In
addition, hypercalcaemia and hypercalciuria have been included as
exclusion/stop criteria to further minimize the risk.
It is important to highlight that even for women receiving 1600 IU/day, after
adding diet and multivitamin supplementation, the UL of the recommended dietary
intake of 4000 IU/day will not be surpassed. We also want to highlight that the
doses used will be lower than those currently used in other trials that have
not reported adverse consequences so far:

*
(http://clinicaltrials.gov/ct2/show/NCT00856947?term=vitamin+D+pregnancy&rank=2,
http://clinicaltrials.gov/ct2/show/NCT00610688?term=vitamin+D+pregnancy&rank=4
* http://clinicaltrials.gov/show/NCT00292591
* http://clinicaltrials.gov/ct2/show/NCT00920621