A Randomized Control Trial of Vitamin D Prophylaxis in the Prevention of Hypertensive Disorders of Pregnancy

NCT ID: NCT02920593

Last Updated: 2017-10-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

412 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-10-31

Study Completion Date

2019-03-31

Brief Summary

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The investigators aim to determine if Vitamin D prophylaxis in pregnancy reduces the incidence of hypertensive disorders of pregnancy.

Detailed Description

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Optimizing Vitamin D status during pregnancy it thought to have maternal, fetal, and neonatal benefit. Studies suggest that Vitamin D acts well beyond its most commonly thought of role in establishing calcium homeostasis and maintaining maternal and neonatal skeletal integrity. Vitamin D has also been found to modulate the maternal renal renin-angiotensin system, maternal immune response, placental implantation and function, and angiogenesis. In light of this, it is no surprise that the 2010 systematic review of vitamin D in pregnancy suggested that Vitamin D deficiency may be associated with an increase risk in maternal and neonatal morbidity. For example, vitamin D deficiency has correlated with an array of maternal conditions, including gestational hypertension, preeclampsia, gestational diabetes, myopathy, vaginal infection, and mental disease. Associated neonatal risks include preterm birth, immunosuppression, infection, low birth weight, hypokalemia, neonatal seizures, asthma, fractures and rickets.

Unfortunately, Vitamin D deficiency in pregnancy is an ongoing epidemic, affecting as many as 82% of pregnant women. While studies on Vitamin D supplementation in pregnancy have consistently shown an associated increase in maternal and neonatal serum Vitamin D levels, some studies have also suggested a concurrent decrease in adverse maternal and neonatal outcomes. For example, Vitamin D supplementation in pregnancies with known deficiency has been shown to decrease the incidence of preeclampsia as much as 32%. Other studies, on the other hand, have suggested no benefit. The inconsistency in findings lie in the fact that these studies were primarily observational in nature and plagued by small sample sizes, recall bias, and inability to adjust for potential confounders. Given this, interpretation regarding clinical significance is limited, preventing providers from making appropriate recommendations to their patients. As such, the American Congress of Obstetricians and Gynecologists (ACOG) has called for high quality studies to address whether the use of Vitamin D supplementation beyond that found in prenatal vitamins is beneficial.

In an effort to elucidate the potential benefit of Vitamin D supplementation in an unscreened population, the investigators propose conducting a randomized control trial in which Vitamin D prophylaxis is provided to a cohort of pregnant women regardless of their Vitamin D status. The aims of the study, therefore, are to:

Specific Aim 1: Determine if Vitamin D prophylaxis in pregnant women decreases the incidence of hypertensive disorders of pregnancy.

Specific Aim 2: Compare neonatal outcomes in those who received Vitamin D prophylaxis to those who did not receive Vitamin D prophylaxis.

Specific Aim 3: Compare placental histology and inflammatory markers in those who received Vitamin D prophylaxis to those who did not receive Vitamin D prophylaxis.

Conditions

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Gestational Hypertension Toxemia Superimposed Preeclampsia Eclampsia HELLP Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Vitamin D Prophylaxis

Participants will be provided Vitamin D 3000 IU daily or Vitamin D 4000 IU daily with and without concurrent use of prenatal vitamins, respectively.

Group Type EXPERIMENTAL

Vitamin D3

Intervention Type DRUG

Vitamin D prophylaxis

No Vitamin D Prophylaxis

Participants will not receive additional Vitamin D in the pregnancy.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Vitamin D3

Vitamin D prophylaxis

Intervention Type DRUG

Other Intervention Names

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Vitamin D

Eligibility Criteria

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Inclusion Criteria

* 18 years of age and older
* With a confirmed intrauterine pregnancy, less than 16 weeks gestation
* Carrying a singleton gestation

Exclusion Criteria

* Taking Vitamin D supplementation outside of prenatal vitamins
* Has a known disorder that will affect vitamin D levels (i.e, hyperparathyroidism, mal-absorption disorder, history of gastric bypass surgery, immunocompromised state, maternal use of immune-modulators etc.)
* Carrying a fetus with known aneuploidy or anomaly
* With fetal demise
* Women with chronic diuretic or cardiac medication therapy including calcium channel blockers
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Stony Brook University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Diana J Garretto, MD

Role: PRINCIPAL_INVESTIGATOR

SUNY Stony Brook Hospital

Locations

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SUNY Stony Brook Hospital

Stony Brook, New York, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Diana J Garretto, MD

Role: CONTACT

(631) 444-7650

Malini D Persad, MD MPH

Role: CONTACT

(631) 444-7650

Facility Contacts

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Diana J Garretto, MD

Role: primary

631-444-7650

Malini D Persad, MD MPH

Role: backup

(631) 444-7650

References

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ACOG Committee Opinion No. 495: Vitamin D: Screening and supplementation during pregnancy. Obstet Gynecol. 2011 Jul;118(1):197-198. doi: 10.1097/AOG.0b013e318227f06b.

Reference Type BACKGROUND
PMID: 21691184 (View on PubMed)

Bodnar LM, Catov JM, Simhan HN, Holick MF, Powers RW, Roberts JM. Maternal vitamin D deficiency increases the risk of preeclampsia. J Clin Endocrinol Metab. 2007 Sep;92(9):3517-22. doi: 10.1210/jc.2007-0718. Epub 2007 May 29.

Reference Type BACKGROUND
PMID: 17535985 (View on PubMed)

Shin JS, Choi MY, Longtine MS, Nelson DM. Vitamin D effects on pregnancy and the placenta. Placenta. 2010 Dec;31(12):1027-34. doi: 10.1016/j.placenta.2010.08.015. Epub 2010 Sep 22.

Reference Type BACKGROUND
PMID: 20863562 (View on PubMed)

Haugen M, Brantsaeter AL, Trogstad L, Alexander J, Roth C, Magnus P, Meltzer HM. Vitamin D supplementation and reduced risk of preeclampsia in nulliparous women. Epidemiology. 2009 Sep;20(5):720-6. doi: 10.1097/EDE.0b013e3181a70f08.

Reference Type BACKGROUND
PMID: 19451820 (View on PubMed)

Urrutia RP, Thorp JM. Vitamin D in pregnancy: current concepts. Curr Opin Obstet Gynecol. 2012 Mar;24(2):57-64. doi: 10.1097/GCO.0b013e3283505ab3.

Reference Type BACKGROUND
PMID: 22327734 (View on PubMed)

Hollis BW, Johnson D, Hulsey TC, Ebeling M, Wagner CL. Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness. J Bone Miner Res. 2011 Oct;26(10):2341-57. doi: 10.1002/jbmr.463.

Reference Type BACKGROUND
PMID: 21706518 (View on PubMed)

Shand AW, Nassar N, Von Dadelszen P, Innis SM, Green TJ. Maternal vitamin D status in pregnancy and adverse pregnancy outcomes in a group at high risk for pre-eclampsia. BJOG. 2010 Dec;117(13):1593-8. doi: 10.1111/j.1471-0528.2010.02742.x. Epub 2010 Oct 13.

Reference Type BACKGROUND
PMID: 21040394 (View on PubMed)

Johnson DD, Wagner CL, Hulsey TC, McNeil RB, Ebeling M, Hollis BW. Vitamin D deficiency and insufficiency is common during pregnancy. Am J Perinatol. 2011 Jan;28(1):7-12. doi: 10.1055/s-0030-1262505. Epub 2010 Jul 16.

Reference Type BACKGROUND
PMID: 20640974 (View on PubMed)

Ringrose JS, PausJenssen AM, Wilson M, Blanco L, Ward H, Wilson TW. Vitamin D and hypertension in pregnancy. Clin Invest Med. 2011 Jun 1;34(3):E147-54. doi: 10.25011/cim.v34i3.15187.

Reference Type BACKGROUND
PMID: 21631991 (View on PubMed)

Powe CE, Seely EW, Rana S, Bhan I, Ecker J, Karumanchi SA, Thadhani R. First trimester vitamin D, vitamin D binding protein, and subsequent preeclampsia. Hypertension. 2010 Oct;56(4):758-63. doi: 10.1161/HYPERTENSIONAHA.110.158238. Epub 2010 Aug 23.

Reference Type BACKGROUND
PMID: 20733087 (View on PubMed)

Specker B. Vitamin D requirements during pregnancy. Am J Clin Nutr. 2004 Dec;80(6 Suppl):1740S-7S. doi: 10.1093/ajcn/80.6.1740S.

Reference Type BACKGROUND
PMID: 15585798 (View on PubMed)

Burton GJ, Sebire NJ, Myatt L, Tannetta D, Wang YL, Sadovsky Y, Staff AC, Redman CW. Optimising sample collection for placental research. Placenta. 2014 Jan;35(1):9-22. doi: 10.1016/j.placenta.2013.11.005. Epub 2013 Nov 19.

Reference Type BACKGROUND
PMID: 24290528 (View on PubMed)

Liu NQ, Kaplan AT, Lagishetty V, Ouyang YB, Ouyang Y, Simmons CF, Equils O, Hewison M. Vitamin D and the regulation of placental inflammation. J Immunol. 2011 May 15;186(10):5968-74. doi: 10.4049/jimmunol.1003332. Epub 2011 Apr 11.

Reference Type BACKGROUND
PMID: 21482732 (View on PubMed)

Androutsopoulos G, Gkogkos P, Decavalas G. Mid-trimester maternal serum HCG and alpha fetal protein levels: clinical significance and prediction of adverse pregnancy outcome. Int J Endocrinol Metab. 2013 Spring;11(2):102-6. doi: 10.5812/ijem.5014. Epub 2013 Apr 1.

Reference Type BACKGROUND
PMID: 23825981 (View on PubMed)

Ertl R, Yu CK, Samaha R, Akolekar R, Nicolaides KH. Maternal serum vitamin D at 11-13 weeks in pregnancies delivering small for gestational age neonates. Fetal Diagn Ther. 2012;31(2):103-8. doi: 10.1159/000333810. Epub 2012 Jan 18.

Reference Type BACKGROUND
PMID: 22261570 (View on PubMed)

De-Regil LM, Palacios C, Lombardo LK, Pena-Rosas JP. Vitamin D supplementation for women during pregnancy. Cochrane Database Syst Rev. 2016 Jan 14;(1):CD008873. doi: 10.1002/14651858.CD008873.pub3.

Reference Type BACKGROUND
PMID: 26765344 (View on PubMed)

Roth DE. Vitamin D supplementation during pregnancy: safety considerations in the design and interpretation of clinical trials. J Perinatol. 2011 Jul;31(7):449-59. doi: 10.1038/jp.2010.203. Epub 2011 Jan 20.

Reference Type BACKGROUND
PMID: 21252966 (View on PubMed)

Other Identifiers

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875799-3

Identifier Type: -

Identifier Source: org_study_id