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AzTrials

Hypovitaminosis DPhase 3NCT02434380

Effect of Vitamin D Replacement on Maternal and Neonatal Outcomes

A Phase 3 study testing Euro D in people with Hypovitaminosis D and Pregnancy Complications, run by American University of Beirut Medical Center at 1 site in Lebanon.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 50 years, women onlyHealthy volunteers can take part
What is being tested?
Euro D
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
330 participants
Where
1 siteLebanon
Study dates
Jul 2015to Oct 2018
Phase
Phase 3
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 to 50 years
  • Women only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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)
  • 25(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.)

Who cannot join

  • 25(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

Trial locations and contacts

1 site in 1 country.

Lebanon1 site

  • American University of Beirut

    Hamra

Other trials in Lebanon

About this study

Official title: Effect of Vitamin D Replacement on Maternal and Neonatal Outcomes: a Randomized Controlled Trial in Pregnant Women With Hypovitaminosis D

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.

Read the detailed description

Hypovitaminosis D is prevalent worldwide across the lifecycle, including pregnant women, and particularly in the Middle East. It has been associated with adverse maternal and neonatal outcomes. While the Institute of Medicine (IOM) recommends 600 IU of vitamin D per day to reach a 25-Hydroxyvitamin D (25(OH)D) level ≥ 20 ng/ml, the Endocrine Society (ES) recommends 1,500-2,000 IU/day to reach a level ≥ 30 ng/ml, and the WHO guidelines do not recommend any supplementation as part of routine prenatal care. They do however underscore the fact that subjects with the lowest levels may be the ones to benefit most from vitamin D replacement. The benefits of such an approach and the doses needed to reach desirable levels have not been tested. This randomized trial proposes to do so, testing the effect of two vitamin D doses, a low dose of 600 IU daily and a high dose of 3,000 IU daily.

330 pregnant women, with 25(OH)D level 10-30 ng/ml during the early second trimester will be recruited form the American University of Beirut-Medical Center (AUB-MC), and Bahman Hospital. They will be randomized, in a double blinded fashion, to receive daily equivalent doses of cholecalciferol, 600 IU or 3,000 IU until delivery. Maternal clinical information and a food frequency questionnaire will be obtained at each visit until delivery. Maternal 25(OH)D and chemistries, including Calcium, creatinine, lipid profile, glucose and Insulin will be assessed at study entry, during third trimester and at delivery. Fetal measurements will be collected at study entry and during the second trimester. Neonatal anthropometric variables and venous umbilical cord 25(OH)D level will be measured at birth and infants will also undergo dual-energy x-ray absorptiometry (DEXA) scan assessment, for bone and fat mass, at one to 6 weeks. Maternal and neonatal genetic studies for vitamin D genes polymorphism, and other modules of placnetal calcium transport will be also performed.

Throughout the study, adverse events will be collected systematically and an independent Data and Safety Monitoring Board will be asked to review serious adverse events.

The percent of women achieving 25(OH)D ≥ 20ng/ml in the low dose will be compared to that in the high dose using Chi-Square. Independent t-test will be used to compare mean neonatal bone mineral content at one month of age between the 2 arms. For other outcomes, t-test will be used for continuous outcomes and Chi-square will be used for binary outcomes to compare means and proportions, respectively. The primary analysis is an intention-to-treat analysis (ITT) of unadjusted results. For the primary outcomes, p- values will be considered statistically significant if ≤ 0.025.

The investigators study would be the only randomized controlled trial in the Middle East, to investigate the recommended daily allowance for vitamin D, and the desirable dose to optimize neonatal musculoskeletal health, in women with low 25(OH)D levels, levels that are reflective of those in most countries from the Middle East.

Being tested
Euro D
Keywords
Vitamin D, Bone mineral content, Knee-heel length, Middle East
Medical subject headings
Vitamin D Deficiency, Pregnancy Complications, Infant, Newborn, Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Euro DDietary supplement

    Also called Europharm

    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.

  • Euro DDietary supplement

    Also called Europharm

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

Study groups in NCT02434380
Study groupRoleWhat they receive
Low dose vitamin DActive comparatorVitamin 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.
Receives: Dietary Supplement: Euro D
High dose vitamin DActive comparatorVitamin D3 Euro D 10,000 IU (2 tablets, equivalent to 20,000 IU) weekly, starting at the second trimester and continued until delivery.
Receives: Dietary Supplement: Euro D

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: At delivery

  2. Infant bone mineral content (BMC)

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

    Measured: one to six weeks

Secondary outcomes (7)

  1. Maternal 25(OH)D level

    We will assess mean maternal 25(OH)D level

    Measured: At delivery

  2. Neonatal 25(OH)D level, at delivery

    We will assess mean neonatal 25(OH)D level

    Measured: At birth

  3. Mean infant fat mass

    We will assess Infant fat mass by whole body dual-energy x-ray absorptiometry (DEXA) scan

    Measured: At one month of age

  4. Neonatal Knee to heel length at birth

    We will assess neonatal Knee to heel length at birth using simple vernier calipers

    Measured: At birth

  5. Maternal Parathyroid Hormone (PTH) Level

    We will assess mean maternal PTH level

    Measured: At delivery

  6. Neonatal Parathyroid Hormone (PTH) Level

    We will assess mean neonatal PTH level

    Measured: At birth

  7. Mean change in maternal urine calcium

    We will assess the change in urine calcium level after 3 months of vitamin D supplementation.

    Measured: Change between baseline and 3 months following intervention

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 May 2015 (estimated)
  2. Study startJul 2015
  3. Primary completionOct 2018
  4. Study completionOct 2018

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
330 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02434380
Sponsor's protocol ID
AUBMC-GE-HF-2
Other IDs
AUBMC-IM-GE-HF-22
Status last verified
Mar 2023
First submitted
27 Apr 2015
Last updated
20 Mar 2023
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 16310641

  • 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.

    PubMed 24194968

  • 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.

    PubMed 20852586

  • 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.

    PubMed 19543765

  • 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.

    PubMed 24874590

  • 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.

    PubMed 16278262

  • 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.

    PubMed 16352684

  • 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.

    PubMed 24123134

  • 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.

    PubMed 23350730

  • 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.

    PubMed 21640968

  • 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.

    PubMed 22623177

  • 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.

    PubMed 22742603

  • 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.

    PubMed 24178796

  • 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.

    PubMed 16399151

  • 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.

    PubMed 21118827

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Euro D in people with Hypovitaminosis D and Pregnancy Complications, run by American University of Beirut Medical Center at 1 site in Lebanon.

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 4 inclusion and 5 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: finished, as of the sponsor's last update on 20 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Lebanon. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The proportions of women who will reach the IOM defined desirable 25(OH)D level ≥20ng/ml. (time frame: At delivery). The study lists 2 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 NCT02434380, which also lists 22 linked publications.

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 20 Mar 2023.

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