Clinical trial NCT02395081: Trial of Vitamin D Supplements to Raise Calcidiol Levels of Pregnant Women in Mongolia
Official title: Trial of Vitamin D Supplements to Raise Calcidiol Levels of Pregnant Women in Mongolia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pregnancy
Vitamin D Deficiency
Keywords: pregnancy
Mongolia
Vitamin D
preeclampsia
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: National Center for Maternal and Child Health Research, Mongolia
name: Zuun Kharaa Hospital
First posted: 2015-03-20
Enrollment: 360
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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 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.

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Total Serum 25(OH)D Concentration
timeFrame: 36 weeks gestation or delivery, if delivery occurred before 36 weeks
Secondary outcomes:
measure: The Number of Participants With Preeclampsia
timeFrame: After 20 weeks gestation
measure: Average Monthly Blood Pressure
timeFrame: During pregnancy
measure: Arterial Tonometry
timeFrame: 36 weeks gestation
measure: Number of Patients With Preterm Delivery as Measured by Clinical Diagnosis
timeFrame: During pregnancy
measure: Casarean Section as Measured by Medical Record Abstraction
timeFrame: Delivery
measure: Assisted Vaginal Delivery as Measured by Medical Record Abstraction
timeFrame: Delivery
measure: Number of Small for Gestational Age (SGA) Neonates as Measured by Medical Record Abstraction
timeFrame: Delivery
measure: Number of Large for Gestational Age (LGA) Neonates as Measured by Medical Record Abstraction
timeFrame: Delivery
measure: Mean Calcemia as Measured by Serum Calcium Test (2mo)
timeFrame: 2 months after randomization
measure: Number of Patients With Proteinuria as Measured by Urine Dipstick
timeFrame: 36-40 weeks gestation/delivery
measure: Number of Patients With Hypertensive Disorders of Pregnancy as Measured by Clinical Diagnosis
timeFrame: During pregnancy
measure: Number of Patients With Bacterial Vaginosis as Measured by Potassium Hydroxide (KOH) Wet Mount
timeFrame: During pregnancy
measure: Mean Calcemia as Measured by Serum Calcium Test (36-40 Weeks)
timeFrame: 36-40 weeks of pregnancy/delivery
Other outcomes:
Locations:
city: Selenge
country: Mongolia
facility: Zuun Kharaa Hospital
state: Selenge Aimag
Study officials:
affiliation: Brigham and Women's Hospital
name: Janet Rich-Edwards, ScD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.