Effect of Vitamin D Replacement on Maternal and Neonatal Outcomes

NCT02434380 | Completed Phase 3 DMC

• 2 other identifiers: AUBMC-GE-HF-2AUBMC-IM-GE-HF-22
• Study Type: interventional
• Target: 330
• Locations: 1 country
• Sites: 1

Brief Summary

The optimal vitamin D replacement dose during pregnancy remains undefined. Therefore, the aim of this study is to test the hypothesis that a daily equivalent dose of vitamin D of 3,000 IU/day is needed for Middle Eastern women, to optimize maternal vitamin D level and neonatal musculoskeletal parameters, specifically knee-heel length at birth and bone mineral content at one month of age.

Conditions

Hypovitaminosis D; Pregnancy Complications; Infant, Newborn, Diseases

Keywords

Vitamin D; Bone mineral content; Knee-heel length; Middle East

Outcome Measures

Primary Outcomes (2)

• The proportions of women who will reach the IOM defined desirable 25(OH)D level ≥20ng/ml.

  At delivery

• Infant bone mineral content (BMC)

  We will assess Infant bone mineral content (BMC) by whole body dual-energy x-ray absorptiometry (DEXA) scan

  one to six weeks

Secondary Outcomes (7)

• Maternal 25(OH)D level

  At delivery

• Neonatal 25(OH)D level, at delivery

  At birth

• Mean infant fat mass

  At one month of age

• Neonatal Knee to heel length at birth

  At birth

• Maternal Parathyroid Hormone (PTH) Level

  At delivery

Other Outcomes (12)

• Composite outcome (incidence of C-section and gestational diabetes mellitus (GDM))

  At delivery

• Maternal weight

  At delivery

• Maternal Blood Pressure (BP)

  At delivery

Study Arms (2)

Low dose vitamin D

ACTIVE COMPARATOR

Vitamin D3 Euro D 10,000 IU (1 tablet) plus Euro D Placebo (1 tablet) weekly, alternating with Euro D Placebo (2 tablets) weekly, starting at the second trimester and continued until delivery.

Dietary Supplement: Euro D

High dose vitamin D

ACTIVE COMPARATOR

Vitamin D3 Euro D 10,000 IU (2 tablets, equivalent to 20,000 IU) weekly, starting at the second trimester and continued until delivery.

Dietary Supplement: Euro D

Interventions

Euro D DIETARY_SUPPLEMENT

Vitamin D3 Euro D 10,000 IU (1 tablet) plus Euro D Placebo (1 tablet) weekly, alternating with Euro D Placebo (2 tablets) weekly, starting at the second trimester and continued until delivery.

Also known as: Europharm

Low dose vitamin D

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Pregnant women gestational age (GA)\< 14 weeks at screening visit. Middle Eastern woman (Middle East countries defined by WHO: Bahrain, Egypt, Iran, Iraq, Palestine, Jordan, Kuwait, Lebanon, Oman, Qatar, Saudi Arabia, Syria, , United Arab Emirates, Yemen)
• (OH)D level between 10ng/ml and 30ng/ml
• Age \> 18 years
• Vitamin D supplementation ≤ 200 IU daily (If daily vitamin D supplementation \> 200 IU daily, at enrollment, the pregnant women will be advised to adjust prenatal multivitamin doses in such a way that total vitamin D supplementation per week doesn't exceed 1400 IU per week, in consultation with primary Obstetric and Gynecology (OB-GYN) physician.)

You may not qualify if:

• (OH)D level \< 10 ng/ml or \> 30 ng/ml.
• Known metabolic bone disease
• Current medications likely to interfere with vitamin D metabolism (enzyme inducing anticonvulsants, anti -TB)
• Vitamin D supplementation \> 600 IU daily
• Pregnant women with twins

Sponsors & Collaborators

• American University of Beirut Medical Center: lead
• University of Southampton: collaborator
• Bahman Hospital Beirut Lebanon: collaborator

Study Sites (1)

American University of Beirut

Hamra, Lebanon

Location

Related Publications (21)

• Kovacs CS, Fuleihan Gel-H. Calcium and bone disorders during pregnancy and lactation. Endocrinol Metab Clin North Am. 2006 Mar;35(1):21-51, v. doi: 10.1016/j.ecl.2005.09.004. No abstract available.

  PMID: 16310641 BACKGROUND

• Bassil D, Rahme M, Hoteit M, Fuleihan Gel-H. Hypovitaminosis D in the Middle East and North Africa: Prevalence, risk factors and impact on outcomes. Dermatoendocrinol. 2013 Apr 1;5(2):274-98. doi: 10.4161/derm.25111.

  PMID: 24194968 BACKGROUND

• Arabi A, El Rassi R, El-Hajj Fuleihan G. Hypovitaminosis D in developing countries-prevalence, risk factors and outcomes. Nat Rev Endocrinol. 2010 Oct;6(10):550-61. doi: 10.1038/nrendo.2010.146.

  PMID: 20852586 BACKGROUND

• Mithal A, Wahl DA, Bonjour JP, Burckhardt P, Dawson-Hughes B, Eisman JA, El-Hajj Fuleihan G, Josse RG, Lips P, Morales-Torres J; IOF Committee of Scientific Advisors (CSA) Nutrition Working Group. Global vitamin D status and determinants of hypovitaminosis D. Osteoporos Int. 2009 Nov;20(11):1807-20. doi: 10.1007/s00198-009-0954-6. Epub 2009 Jun 19.

  PMID: 19543765 BACKGROUND

• Hoteit M, Al-Shaar L, Yazbeck C, Bou Sleiman M, Ghalayini T, Fuleihan Gel-H. Hypovitaminosis D in a sunny country: time trends, predictors, and implications for practice guidelines. Metabolism. 2014 Jul;63(7):968-78. doi: 10.1016/j.metabol.2014.04.009. Epub 2014 Apr 23.

  PMID: 24874590 BACKGROUND

• El-Hajj Fuleihan G, Nabulsi M, Tamim H, Maalouf J, Salamoun M, Khalife H, Choucair M, Arabi A, Vieth R. Effect of vitamin D replacement on musculoskeletal parameters in school children: a randomized controlled trial. J Clin Endocrinol Metab. 2006 Feb;91(2):405-12. doi: 10.1210/jc.2005-1436. Epub 2005 Nov 8.

  PMID: 16278262 BACKGROUND

• Morley R, Carlin JB, Pasco JA, Wark JD. Maternal 25-hydroxyvitamin D and parathyroid hormone concentrations and offspring birth size. J Clin Endocrinol Metab. 2006 Mar;91(3):906-12. doi: 10.1210/jc.2005-1479. Epub 2005 Dec 13.

  PMID: 16352684 BACKGROUND

• Al-Shaar L, Mneimneh R, Nabulsi, Maalouf J, Fuleihan Gel-H. Vitamin D3 dose requirement to raise 25-hydroxyvitamin D to desirable levels in adolescents: results from a randomized controlled trial. J Bone Miner Res. 2014 Apr;29(4):944-51. doi: 10.1002/jbmr.2111.

  PMID: 24123134 BACKGROUND

• Parkes I, Schenker JG, Shufaro Y. Parathyroid and calcium metabolism disorders during pregnancy. Gynecol Endocrinol. 2013 Jun;29(6):515-9. doi: 10.3109/09513590.2012.754880. Epub 2013 Jan 25.

  PMID: 23350730 BACKGROUND

• Nassar N, Halligan GH, Roberts CL, Morris JM, Ashton AW. Systematic review of first-trimester vitamin D normative levels and outcomes of pregnancy. Am J Obstet Gynecol. 2011 Sep;205(3):208.e1-7. doi: 10.1016/j.ajog.2011.03.058. Epub 2011 Apr 7.

  PMID: 21640968 BACKGROUND

• Hollis BW, Wagner CL. Vitamin D and pregnancy: skeletal effects, nonskeletal effects, and birth outcomes. Calcif Tissue Int. 2013 Feb;92(2):128-39. doi: 10.1007/s00223-012-9607-4. Epub 2012 May 24.

  PMID: 22623177 BACKGROUND

• Thorne-Lyman A, Fawzi WW. Vitamin D during pregnancy and maternal, neonatal and infant health outcomes: a systematic review and meta-analysis. Paediatr Perinat Epidemiol. 2012 Jul;26 Suppl 1(0 1):75-90. doi: 10.1111/j.1365-3016.2012.01283.x.

  PMID: 22742603 BACKGROUND

• Harvey NC, Moon RJ, Sayer AA, Ntani G, Davies JH, Javaid MK, Robinson SM, Godfrey KM, Inskip HM, Cooper C; Southampton Women's Survey Study Group. Maternal antenatal vitamin D status and offspring muscle development: findings from the Southampton Women's Survey. J Clin Endocrinol Metab. 2014 Jan;99(1):330-7. doi: 10.1210/jc.2013-3241. Epub 2013 Dec 20.

  PMID: 24178796 BACKGROUND

• Javaid MK, Crozier SR, Harvey NC, Gale CR, Dennison EM, Boucher BJ, Arden NK, Godfrey KM, Cooper C; Princess Anne Hospital Study Group. Maternal vitamin D status during pregnancy and childhood bone mass at age 9 years: a longitudinal study. Lancet. 2006 Jan 7;367(9504):36-43. doi: 10.1016/S0140-6736(06)67922-1.

  PMID: 16399151 BACKGROUND

• Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011 Jan;96(1):53-8. doi: 10.1210/jc.2010-2704. Epub 2010 Nov 29.

  PMID: 21118827 BACKGROUND

• Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM; Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Jul;96(7):1911-30. doi: 10.1210/jc.2011-0385. Epub 2011 Jun 6.

  PMID: 21646368 BACKGROUND

• Harvey N, Dennison E, Cooper C. Osteoporosis: a lifecourse approach. J Bone Miner Res. 2014 Sep;29(9):1917-25. doi: 10.1002/jbmr.2286.

  PMID: 24861883 BACKGROUND

• De-Regil LM, Palacios C, Ansary A, Kulier R, Pena-Rosas JP. Vitamin D supplementation for women during pregnancy. Cochrane Database Syst Rev. 2012 Feb 15;2(2):CD008873. doi: 10.1002/14651858.CD008873.pub2.

  PMID: 22336854 BACKGROUND

• 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. Erratum In: J Bone Miner Res. 2011 Dec; 26(12):3001.

  PMID: 21706518 BACKGROUND

• Dawodu A, Saadi HF, Bekdache G, Javed Y, Altaye M, Hollis BW. Randomized controlled trial (RCT) of vitamin D supplementation in pregnancy in a population with endemic vitamin D deficiency. J Clin Endocrinol Metab. 2013 Jun;98(6):2337-46. doi: 10.1210/jc.2013-1154. Epub 2013 Apr 4.

  PMID: 23559082 BACKGROUND

• Chakhtoura M, Nassar A, Arabi A, Cooper C, Harvey N, Mahfoud Z, Nabulsi M, El-Hajj Fuleihan G. Effect of vitamin D replacement on maternal and neonatal outcomes: a randomised controlled trial in pregnant women with hypovitaminosis D. A protocol. BMJ Open. 2016 Mar 8;6(3):e010818. doi: 10.1136/bmjopen-2015-010818.

  PMID: 26956166 DERIVED

Related Links

• Calcium Metabolism and Osteoporosis Program, American University of Beirut

MeSH Terms

Conditions

Vitamin D Deficiency; Pregnancy Complications; Infant, Newborn, Diseases

Condition Hierarchy (Ancestors)

Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Ghada El Hajj Fuleihan, Professor of Medicine

  American University of Beirut Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: April 27, 2015
• First Posted: May 5, 2015
• Study Start: July 1, 2015
• Primary Completion: October 1, 2018
• Study Completion: October 1, 2018
• Last Updated: March 20, 2023

Record last verified: 2023-03

Locations

LE (1)