PregnancyNCT02395081
Trial of Vitamin D Supplements to Raise Calcidiol Levels of Pregnant Women in Mongolia
A study testing 600 IU Vitamin D3 in prenatal vitamin, 2000 IU Vitamin D3 in prenatal vitamin and 4000 IU Vitamin D3 in prenatal vitamin in people with Pregnancy and Vitamin D Deficiency, run by Brigham and Women's Hospital at 1 site in Mongolia.
Trial summary
A double-blind randomized, placebo-controlled trial comparing the impact of 600 IU, 2000 IU, or 4000 IU of Vitamin D3 on third trimester 25(OH)D levels and change from baseline. The Vitamin D will be integrated in a standard prenatal vitamin, which will be taken from 12-16 weeks' gestation and continue throughout… 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
- Pregnancy, Vitamin D Deficiency
- What is being tested?
- 600 IU Vitamin D3 in prenatal vitamin, 2000 IU Vitamin D3 in prenatal vitamin and 4000 IU Vitamin D3 in prenatal vitamin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 360 participants
- Where
- 1 siteMongolia
- Study dates
- Feb 2015to Dec 2016
- Phase
- Interventional
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
- Age 18 or older
- 12-16 weeks pregnant
- Receiving prenatal care at Zuun Kharaa Hospital and planning to deliver at Zuun Kharaa Hospital
- Willing not to take any additional vitamin D supplements, other than the study dispensed pills
Who cannot join
- Existing known seizure disorder, renal failure, parathyroid disease, thyroid disease, sarcoidosis, cancer, or tuberculosis. (Tuberculosis is routinely screened in pregnancy)
- History of kidney stones
- Known sensitivity to multivitamin preparations
- Taking vitamin D supplements containing >600 IU/day.
Trial locations and contacts
1 site in 1 country.
About this study
A double-blind randomized, placebo-controlled trial comparing the impact of 600 IU, 2000 IU, or 4000 IU of Vitamin D3 on third trimester 25(OH)D levels and change from baseline. The Vitamin D will be integrated in a standard prenatal vitamin, which will be taken from 12-16 weeks' gestation and continue throughout pregnancy. Umbilical cord 25(OH)D levels will also be determined. The investigators will generate preliminary data regarding Vitamin D intake and hypertensive disorders, blood pressure, and arterial function measured by tonography. The investigators will independently test blood pressure and proteinuria to identify preeclampsia cases.
Read the detailed description
Vitamin D deficiency (serum 25(OH)D levels <20 ng/ml or 50 nmol/l) is widespread among Mongolians and is nearly universal during the winter months. The investigators have conducted a series of studies which have shown nearly universal Vitamin D deficiency in the winter months.
Observational studies in the U.S. have linked low 25(OH)D levels in women to a higher risk of preeclampsia. Mongolians also report levels of preeclampsia that are 3 times higher than those in the U.S (official reports cite 15%, though this may include gestational hypertension).
Given the widespread Vitamin D deficiency in Mongolian women, the high prevalence of hypertensive pregnancy in Mongolia, and the observational studies linking low 25(OH)D levels with preeclampsia risk, the investigators are conducting a pilot Vitamin D dosing trial to:
- Determine what level of Vitamin D supplementation is needed to secure 25(OH)D levels of at least 20 ng/ml in pregnant Mongolian women
- Generate preliminary data in support of a funding application for a larger trial of Vitamin D supplements to prevent preeclampsia in Mongolia
A double-blind randomized, placebo-controlled trial comparing the impact of 600 IU, 2000 IU, or 4000 IU of Vitamin D3 on third trimester 25(OH)D levels and change from baseline. The Vitamin D will be integrated in a standard prenatal vitamin, which will be taken from 12-16 weeks' gestation and continue throughout pregnancy. Umbilical cord 25(OH)D levels will also be determined. The investigators will generate preliminary data regarding Vitamin D intake and hypertensive disorders, blood pressure, and arterial function measured by tonography. The investigators will independently test blood pressure and proteinuria to identify preeclampsia cases.
The investigators will enroll 360 women who plan to receive their prenatal care and deliver at Zuun Kharaa Hospital in the Selenge province in northern Mongolia. Enrollment will be stratified by season. 120 women will be randomized to each of the three doses of vitamin D (600, 2000, 4000 IU) included in a standard prenatal vitamin.
Calcemia will be monitored two months after randomization and weeks 36-40 of pregnancy. Adverse events of pregnancy will be reported to the Data Safety and Monitoring Board (DSMB) and Institutional Review Board (IRB) per protocol.
Data will be gathered by a Mongolian study coordinator and local clinicians. A DSMB comprised of a U.S. and Mongolian clinicians and statisticians will monitor study data for safety.
- Conditions
- Pregnancy, Vitamin D Deficiency
- Being tested
- 600 IU Vitamin D3 in prenatal vitamin, 2000 IU Vitamin D3 in prenatal vitamin, 4000 IU Vitamin D3 in prenatal vitamin
- Keywords
- pregnancy, Mongolia, Vitamin D, preeclampsia
- Medical subject headings
- Vitamin D Deficiency, Pre-Eclampsia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
600 IU Vitamin D3 in prenatal vitaminDietary supplement
Women will receive 600 IU 25(OH)D in prenatal vitamin.
2000 IU Vitamin D3 in prenatal vitaminDietary supplement
Women will receive 2000 IU 25(OH)D in prenatal vitamin.
4000 IU Vitamin D3 in prenatal vitaminDietary supplement
Women will receive 4000 IU 25(OH)D in prenatal vitamin.
| Study group | Role | What they receive |
|---|---|---|
| 600 IU | Placebo comparator | Women will receive prenatal vitamins containing 600 IU of Vitamin D. Receives: Dietary Supplement: 600 IU Vitamin D3 in prenatal vitamin |
| 2000 IU | Experimental | Women will receive prenatal vitamins containing 2000 IU of Vitamin D. Receives: Dietary Supplement: 2000 IU Vitamin D3 in prenatal vitamin |
| 4000 IU | Experimental | Women will receive prenatal vitamins containing 4000 IU of Vitamin D. Receives: Dietary Supplement: 4000 IU Vitamin D3 in prenatal vitamin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Serum 25(OH)D Concentration
Circulating vitamin D at the end of the study as measured by VIDAS® enzyme linked fluorescent assay (ELFA)
Measured: 36 weeks gestation or delivery, if delivery occurred before 36 weeks
Secondary outcomes (13)
The Number of Participants With Preeclampsia
Preeclampsia as measured by new onset hypertension after 20 weeks gestation and proteinuria.
Measured: After 20 weeks gestation
Average Monthly Blood Pressure
Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) were measured in mm Hg at each antenatal care visit by the Study Coordinator, using the Omron- Elite 7300 (Omron Healthcare, Bannockburn, Illinois, USA) automated blood pressure monitor. Three blood pressure readings were taken after at least five minutes seated rest. For the analysis of mean blood pressures at each antenatal visit, the three readings were averaged for each participant.
Measured: During pregnancy
Arterial Tonometry
Investigators will assess Augmentation Index (AIx) and Pulse Wave Velocity (PWV) by study arm, as measured by AtCor Medical SphygmoCor device. THIS TONOMETER FAILED AND COULD NOT BE REPAIRED, SO WE ARE NOT PRESENTING THESE DATA AS OUTCOMES.
Measured: 36 weeks gestation
Number of Patients With Preterm Delivery as Measured by Clinical Diagnosis
Gestational age was determined clinically by last menstrual period and by routine first trimester ultrasound which was universal; where these differed by more than 10 days, the ultrasound date was used. Gestational age at delivery was recorded by clinicians and rounded to the nearest week. Preterm delivery was defined as delivery before the 37th week of gestation.
Measured: During pregnancy
Casarean Section as Measured by Medical Record Abstraction
Cesarean section was abstracted from the labor and delivery chart.
Measured: Delivery
Assisted Vaginal Delivery as Measured by Medical Record Abstraction
Assisted vaginal delivery with forceps delivery was abstracted from the labor and delivery chart.
Measured: Delivery
Number of Small for Gestational Age (SGA) Neonates as Measured by Medical Record Abstraction
SGA defined by the lowest 10th percentiles of sex-specific birthweight for gestational age charts of the INTERGROWTH-21st study
Measured: Delivery
Number of Large for Gestational Age (LGA) Neonates as Measured by Medical Record Abstraction
LGA defined by the highest 10th percentiles of sex-specific birthweight for gestational age charts of the INTERGROWTH-21st study
Measured: Delivery
Mean Calcemia as Measured by Serum Calcium Test (2mo)
Measured on a semi-automated photometer (Humalyzer 3500, Human Diagnostics, Magdeburg, Germany)
Measured: 2 months after randomization
Number of Patients With Proteinuria as Measured by Urine Dipstick
Proteinuria at last antenatal visit (usually 36-40 weeks' gestation), measured by 1+ Standard Diagnostics UroColor 10 10 (Kyonggi-do, South Korea) reagent strips
Measured: 36-40 weeks gestation/delivery
Number of Patients With Hypertensive Disorders of Pregnancy as Measured by Clinical Diagnosis
In Mongolia, clinician-diagnosed preeclampsia may include a blood pressure increases >30 mm Hg above early pregnancy, with or without documented hypertension, proteinuria, or symptoms such as headache and edema
Measured: During pregnancy
Number of Patients With Bacterial Vaginosis as Measured by Potassium Hydroxide (KOH) Wet Mount
Bacterial vaginosis was routinely screened by potassium hydroxide wet mount at the first antenatal visit, at 28 weeks' and 32 weeks' gestation. It was also diagnosed by whiff test. We included both wet mount and whiff test positive in the bacterial vaginosis endpoint
Measured: During pregnancy
Mean Calcemia as Measured by Serum Calcium Test (36-40 Weeks)
Measured on a semi-automated photometer (Humalyzer 3500, Human Diagnostics, Magdeburg, Germany)
Measured: 36-40 weeks of pregnancy/delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2015 (estimated)
- Study startFeb 2015
- Primary completionDec 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PregnancyStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 360 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Center for Maternal and Child Health, Mongolia, Zuun Kharaa Hospital
- Responsible party
- Principal investigator, Janet Rich-Edwards, Brigham and Women's Hospital
- Investigators
- Janet Rich-Edwards, ScD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02395081
- Sponsor's protocol ID
- 14-0591-02
- Status last verified
- Feb 2021
- First submitted
- 11 Feb 2015
- Last updated
- 23 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Enkhmaa D, Tanz L, Ganmaa D, Enkhtur S, Oyun-Erdene B, Stuart J, Chen G, Carr A, Seely EW, Fitzmaurice G, Buyandelger Y, Sarantsetseg B, Gantsetseg G, Rich-Edwards J. Randomized trial of three doses of vitamin D to reduce deficiency in pregnant Mongolian women. EBioMedicine. 2019 Jan;39:510-519. doi: 10.1016/j.ebiom.2018.11.060. Epub 2018 Dec 11.
PubMed 30552064