Vitamin D DeficiencyGRAVITDNCT04291313
Vitamin D in Pregnancy
A study testing Vitamin D3 (90µg) and Vitamin D3 (10µg) in people with Vitamin D Deficiency and Pre-Eclampsia, run by University of Aarhus at 2 sites in Denmark.
Trial summary
Danish pregnant women are recommended ad daily vitamin D supplement of 10 µg. Despite the fact that 9 out of 10 women take vitamin D supplements, more than 40% of pregnant women are vitamin D deficient, putting them at an increased risk of pregnancy complications like fetal growth restriction and pre-eclampsia. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Vitamin D Deficiency, Pre-Eclampsia, Fetal Growth Retardation
- What is being tested?
- Vitamin D3 (90µg) and Vitamin D3 (10µg)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2,000 participants
- Where
- 2 sitesDenmark
- Study dates
- 8 Jun 2020to May 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- All pregnant women attending the nuchal translucency scan in week 11-13 of gestation as part of the national prenatal screening program
Who cannot join
- Age< 18 years
- Women with calcium metabolism disorders,
- Women who gets doctor prescribed vitamin D treatment
- Women with chronic kidney disease
Trial locations and contacts
2 sites in 1 country.
Denmark2 sites, 1 recruiting
- Active, not recruiting
Department of Biomedicine, University of Aarhus
Aarhus, DK-8000
- Recruiting
Randers Regional Hospital
Randers, DK-8930
Pinar Bor, MD, PhD, isipinbo@rm.dk
Anna Louise Vestergaard, MD, annavt@rm.dk
About this study
Official title: Vitamin D Deficiency in Pregnancy - Identifying Associations and Mechanisms Linking Maternal Vitamin D Deficiency to Placental Dysfunction and Adverse Pregnancy Outcomes
Danish pregnant women are recommended ad daily vitamin D supplement of 10 µg. Despite the fact that 9 out of 10 women take vitamin D supplements, more than 40% of pregnant women are vitamin D deficient, putting them at an increased risk of pregnancy complications like fetal growth restriction and pre-eclampsia. Our hypothesis is that pregnant women would benefit from an increased intake og vitamin D and that an intake of 90µg/day can reduce the prevalence of placenta-related pregnancy complications. Combining a double-blinded randomized trial (10µg vs.90µg) with collection of placental material, we want to test if the prevalence of pregnancy complications is reduced and explore how vitamin D affects placenta to improve our understanding of the disease pathology and risk factors.
Read the detailed description
As vitamin D (vit-D) is essential for growth and linked to placental function, health authorities recommend a daily 10µg vit-D supplement in pregnancy. Despite the fact that 9 out of 10 women take supplements, more than 40% of pregnant women are vit-D deficient, putting them at an increased risk of pregnancy complications like fetal growth restriction and pre-eclampsia. These conditions affect 6-10 % of all pregnancies, increasing the risk of preterm delivery, perinatal morbidity and mortality. In worse case, preeclampsia may also be fatal for the pregnant women herself. Around 20% of vit-D intake comes from the diet (e.g. fish, egg yolk) and the rest from sun-exposure. However, in Denmark, there is not enough sunlight from October to March to fuel vit-D synthesis underlining the need for supplementation. The high prevalence of vit-D deficiency indicates that current guidelines are not sufficient. Indeed, today´s recommendations date back to a small-scale 1986 Norwegian study not taking into account dietary differences such as the high intake of fish in Norway. Since then, accumulating evidence has linked exposure to pregnancy complications and vit-D deficiency per see to long-term health problems in the affected children. This include a higher risk of asthma, cardiovascular disease, diabetes, obesity schizophrenia, neurodevelopmental problems and multiple sclerosis. Notably, the affected women also suffer an increased risk of disease, e.g. heart disease in later life. Vitamin D supplements in the range of 90-100 µg are safe in pregnancy, but it is not yet known if and to what extent increased vitamin D supplementation prevents pregnancy-related diseases. Combining clinical testing of 90 µg vitamin D supplements, with identification of which placental pathways that are affected by vit-D would considerably improve our understanding of disease pathophysiology and the role of vit-D and improve the health of future generations in an easily implementable way.
- Being tested
- Vitamin D3 (90µg), Vitamin D3 (10µg)
- Medical subject headings
- Vitamin D Deficiency, Pre-Eclampsia, Fetal Growth Retardation, Diabetes, Gestational
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin D3 (90µg)Dietary supplement
The intervention is a higher dose of vitamin D than what is currently recommended to Danish pregnant women
Vitamin D3 (10µg)Dietary supplement
This intervention serves as a control as they get the current recommended vitamin D dose
| Study group | Role | What they receive |
|---|---|---|
| Current recommended dose of vitamin D | Placebo comparator | Women in this study arm receive 10 µg of vitamin D3 per day, which is the dose in a standard prenatal multivitamin and the dose currently recommended by the Danish Health Authorities to all pregnant women. They will receive a prenatal vitamin containing 10µg of vitamin D + a placebo supplement. Receives: Dietary Supplement: Vitamin D3 (10µg) |
| Higher dose of vitamin D | Experimental | Women in this arm receive 90µg of vitamin D3 per day: 10 µg from a standard prenatal multivitamin + an additional supplement containing 80µg of vitamin D3. Receives: Dietary Supplement: Vitamin D3 (90µg) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The prevalence of pre-eclampsia (PE)
The effect of 90 μg on the prevalence of PE
Measured: From 20 weeks of gestation to delivery
The prevalence of fetal growth retardation (FGR)
The effect of 90 μg on the prevalence of FGR
Measured: From 20 weeks of gestation to delivery
The prevalence of gestational diabetes (GDM)
The effect of 90 μg on the prevalence of GDM
Measured: From 20 weeks of gestation to delivery
Secondary outcomes (11)
Changes in the placental expression of genes- and proteins related to vitamin D, evaluated using Next Generation Sequencing (NGS), quantitative Polymerase Chain Reaction (qPCR), methylation (Bisulfite conversion) and western blotting.
Characterization of the changes in the placenta as a result of vitamin D deficiency in healthy women including evaluation of the effect of BMI on placental function and vitamin D metabolism.
NGS will be used to obtain a pathway analysis of differences between groups. Important findings from NGS will be verified on genetic and protein levels by qPCR and Western blotting respectively. Findings from NGS, qPCR and western blotting will be combined to characterize the changes in placentas from vitamin D deficient women compared to vitamin D sufficient women stratified by BMI.
Further, changes in the expression of pivotal genes/proteins related to vitamin D metabolism (CYP2R1, CYP27B1, CYP24A1, Vitamin D receptor) will be investigated using qPCR, methylation analysis and western blotting. Findings from qPCR (gene level) methylation (gene level) and western blotting (protein level) are combined to characterize changes in placentas.
Analyses will be done in subgroups of participants
Measured: At delivery
Changes in the placental expression of genes- and proteins related to vitamin D and the pathogenesis of PE, FGR and GDM in placental tissue from complicated pregnancies compared to uncomplicated pregnancies, evaluated using NGS, qPCR and western blotting
Identification of changes in placental expression of genes and proteins related to the pathogenesis of PE, FGR and GDM and their relationship to vitamin D sensitive placental functions in complicated pregnancies (PE, FGR, GDM) compared to healthy uncomplicated pregnancies.
NGS will be used to obtain a pathway analysis of differences in the gene expression between complicated pregnancies (PE, FGR, GDM) and healthy uncomplicated pregnancies. Important findings from the NGS studies will be verified on genetic and protein levels by qPCR and Western blotting. Findings from the NGS and the verifying results from qPCR (gene level) and western blotting (protein level) will be combined to characterize the changes in placentas from complicated pregnancies (PE, FGR, GDM) compared to healthy uncomplicated pregnancies.
Analyses will be done in subgroups of participants
Measured: At delivery
Birthweight
The effect of 90 μg vitamin D on birthweight.
Measured: At delivery
Size related to gestational age
The effect of 90 μg vitamin D on size related to gestational age (Small for Gestational Age;SGA, Appropriate for Gestational Age; AGA, Large for Gestational Age;LGA)
Measured: At delivery
The prevalence of preterm birth
The effect of 90 μg vitamin D on the prevalence of preterm birth (birth < 37 weeks of gestation).
Measured: At delivery
The prevalence of postterm birth
The effect of 90 μg vitamin D on the prevalence of postterm birth (birth > 40 weeks of gestation)
Measured: At delivery
The prevalence of gestational hypertension
The effect of 90 μg vitamin D on the prevalence of gestational hypertension (>140/90)
Measured: From 20 weeks of gestation to delivery
Mode of delivery
Mode of delivery
Measured: At delivery
The prevalence of infection during delivery
Infection during delivery (incl. use of antibiotics)
Measured: At delivery
Admission to the neonatal ward
Admission of the new born child to the neonatal ward
Measured: The first two weeks after birth
Prevalence of post partum hemorrhage > 500 ml
The effect of 90 μg vitamin D on the prevalence of post partum hemorrhage > 500 ml
Measured: The first 24 hours after delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2020
- Study start8 Jun 2020
- Primary completionFeb 2023 (estimated)
- Study completionMay 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Vitamin D DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 2,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04291313
- Sponsor's protocol ID
- GRAVITD
- Acronym
- GRAVITD
- Status last verified
- Apr 2021
- First submitted
- 17 Feb 2020
- Last updated
- 28 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Vestergaard AL, Christensen M, Andreasen MF, Larsen A, Bor P. Vitamin D in pregnancy (GRAVITD) - a randomised controlled trial identifying associations and mechanisms linking maternal Vitamin D deficiency to placental dysfunction and adverse pregnancy outcomes - study protocol. BMC Pregnancy Childbirth. 2023 Mar 15;23(1):177. doi: 10.1186/s12884-023-05484-x.
PubMed 36922777
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vitamin D Deficiency in Pregnancy - Identifying Associations and Mechanisms Linking Maternal Vitamin D Deficiency to Placental Dysfunction and Adverse Pregnancy Outcomes
- ClinicalTrials.gov ID
- NCT04291313
- Acronym / sponsor ID
- GRAVITD / GRAVITD
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 2,000 participants (estimated)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Study start
- 8 Jun 2020 (actual)
- Primary completion
- Feb 2023 (estimated)
- Study completion
- May 2023 (estimated)
- First posted
- 2 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Danish pregnant women are recommended ad daily vitamin D supplement of 10 µg. Despite the fact that 9 out of 10 women take vitamin D supplements, more than 40% of pregnant women are vitamin D deficient, putting them at an increased risk of pregnancy complications like fetal growth restriction and pre-eclampsia. Our hypothesis is that pregnant women would benefit from an increased intake og vitamin D and that an intake of 90µg/day can reduce the prevalence of placenta-related pregnancy complications. Combining a double-blinded randomized trial (10µg vs.90µg) with collection of placental material, we want to test if the prevalence of pregnancy complications is reduced and explore how vitamin D affects placenta to improve our understanding of the disease pathology and risk factors.
Detailed description
As vitamin D (vit-D) is essential for growth and linked to placental function, health authorities recommend a daily 10µg vit-D supplement in pregnancy. Despite the fact that 9 out of 10 women take supplements, more than 40% of pregnant women are vit-D deficient, putting them at an increased risk of pregnancy complications like fetal growth restriction and pre-eclampsia. These conditions affect 6-10 % of all pregnancies, increasing the risk of preterm delivery, perinatal morbidity and mortality. In worse case, preeclampsia may also be fatal for the pregnant women herself. Around 20% of vit-D intake comes from the diet (e.g. fish, egg yolk) and the rest from sun-exposure. However, in Denmark, there is not enough sunlight from October to March to fuel vit-D synthesis underlining the need for supplementation. The high prevalence of vit-D deficiency indicates that current guidelines are not sufficient. Indeed, today´s recommendations date back to a small-scale 1986 Norwegian study not taking into account dietary differences such as the high intake of fish in Norway. Since then, accumulating evidence has linked exposure to pregnancy complications and vit-D deficiency per see to long-term health problems in the affected children. This include a higher risk of asthma, cardiovascular disease, diabetes, obesity schizophrenia, neurodevelopmental problems and multiple sclerosis. Notably, the affected women also suffer an increased risk of disease, e.g. heart disease in later life. Vitamin D supplements in the range of 90-100 µg are safe in pregnancy, but it is not yet known if and to what extent increased vitamin D supplementation prevents pregnancy-related diseases. Combining clinical testing of 90 µg vitamin D supplements, with identification of which placental pathways that are affected by vit-D would considerably improve our understanding of disease pathophysiology and the role of vit-D and improve the health of future generations in an easily implementable way.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Current recommended dose of vitamin D | Placebo comparator | Dietary Supplement: Vitamin D3 (10µg)Women in this study arm receive 10 µg of vitamin D3 per day, which is the dose in a standard prenatal multivitamin and the dose currently recommended by the Danish Health Authorities to all pregnant women. They will receive a prenatal vitamin containing 10µg of vitamin D + a placebo supplement. |
| Higher dose of vitamin D | Experimental | Dietary Supplement: Vitamin D3 (90µg)Women in this arm receive 90µg of vitamin D3 per day: 10 µg from a standard prenatal multivitamin + an additional supplement containing 80µg of vitamin D3. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- All pregnant women attending the nuchal translucency scan in week 11-13 of gestation as part of the national prenatal screening program
Key exclusion criteria (4 listed)
- Age< 18 years
- Women with calcium metabolism disorders,
- Women who gets doctor prescribed vitamin D treatment
- Women with chronic kidney disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vitamin D3 (90µg)The intervention is a higher dose of vitamin D than what is currently recommended to Danish pregnant women | Dietary supplement | Higher dose of vitamin D |
| Vitamin D3 (10µg)This intervention serves as a control as they get the current recommended vitamin D dose | Dietary supplement | Current recommended dose of vitamin D |
Primary outcome
The prevalence of pre-eclampsia (PE)
Time frame: From 20 weeks of gestation to delivery
The effect of 90 μg on the prevalence of PE
The prevalence of fetal growth retardation (FGR)
Time frame: From 20 weeks of gestation to delivery
The effect of 90 μg on the prevalence of FGR
The prevalence of gestational diabetes (GDM)
Time frame: From 20 weeks of gestation to delivery
The effect of 90 μg on the prevalence of GDM
11 secondary outcomes
Changes in the placental expression of genes- and proteins related to vitamin D, evaluated using Next Generation Sequencing (NGS), quantitative Polymerase Chain Reaction (qPCR), methylation (Bisulfite conversion) and western blotting.
Time frame: At delivery
Changes in the placental expression of genes- and proteins related to vitamin D and the pathogenesis of PE, FGR and GDM in placental tissue from complicated pregnancies compared to uncomplicated pregnancies, evaluated using NGS, qPCR and western blotting
Time frame: At delivery
Birthweight
Time frame: At delivery
Size related to gestational age
Time frame: At delivery
The prevalence of preterm birth
Time frame: At delivery
The prevalence of postterm birth
Time frame: At delivery
The prevalence of gestational hypertension
Time frame: From 20 weeks of gestation to delivery
Mode of delivery
Time frame: At delivery
The prevalence of infection during delivery
Time frame: At delivery
Admission to the neonatal ward
Time frame: The first two weeks after birth
Prevalence of post partum hemorrhage > 500 ml
Time frame: The first 24 hours after delivery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2021.
- Derived from this study: PubMed 36922777Vestergaard AL, Christensen M, Andreasen MF, Larsen A, Bor P. Vitamin D in pregnancy (GRAVITD) - a randomised controlled trial identifying associations and mechanisms linking maternal Vitamin D deficiency to placental dysfunction and adverse pregnancy outcomes - study protocol. BMC Pregnancy Childbirth. 2023 Mar 15;23(1):177. doi: 10.1186/s12884-023-05484-x.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vitamin D3 (90µg) and Vitamin D3 (10µg) in people with Vitamin D Deficiency and Pre-Eclampsia, run by University of Aarhus at 2 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Anna Louise Vestergaard, MD (+45 28951794, alv@clin.au.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The prevalence of pre-eclampsia (PE) (time frame: From 20 weeks of gestation to delivery). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04291313, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2021.