Maternal Vitamin D for Infant Growth (MDIG) Trial

NCT01924013 | Completed Phase 3 DMC

• 1 other identifier: 1000039072
• Study Type: interventional
• Target: 1,300
• Locations: 1 country
• Sites: 1

Brief Summary

The primary aims of this study are: 1) to determine whether maternal prenatal vitamin D3 supplementation (4200 IU/week, 16,800 IU/week, or 28,000 IU/week) versus placebo increases or decreases infant length at 1 year of age, and 2) to determine whether maternal postpartum vitamin D3 supplementation (28,000 IU/week) versus placebo increases or decreases length at 1 year of age among infants born to women who received vitamin D 28,000 U/week during pregnancy. Infants enrolled in the study will be followed for 2 years to document the persistence of any observed effects measured at 1 year of age. This study aims to enroll 1300 pregnant women in the 2nd trimester at a maternity hospital in Dhaka. Participants will be randomized to one of three doses of vitamin D3 (4200 IU/week, 16,800 IU/week, or 28,000 IU/week) or placebo throughout pregnancy. Women in the 28,000 IU/week group will be additionally randomized to either placebo or a continuation of 28,000 IU/week for 6 months postpartum. In addition to linear length, the trial will include analyses of inflammatory and hormonal determinants of infant growth, epigenetic phenomena that affect vitamin D metabolism, and diarrheal and respiratory morbidity in the infants.

Conditions

Pregnancy

Keywords

Pregnancy; Infant Growth; Vitamin D; Bangladesh

Outcome Measures

Primary Outcomes (2)

• Infant Length-for-Age Z-Scores with Prenatal Supplementation

  1 year of age

• Infant Length-for-Age Z-Scores with Postpartum Supplementation

  A separate analysis will be performed to assess the effect of continuation of 28,000 IU/week postpartum supplementation versus placebo (postpartum) among participants randomized to 28,000 IU/week prenatal.

  1 year of age

Secondary Outcomes (1)

• Serum calcium

  17 weeks gestation to birth (prenatal) and over 2 years postpartum

Other Outcomes (9)

• Stunting (LAZ < -2 SD below the median) at 1 and 2 years of age.

  1-2 years

• Attained length and LAZ at 2 years of age.

  2 years postnatal

• Birth weight, low birth weight %, small-for-gestational age %

  Birth

Study Arms (5)

Group A

PLACEBO COMPARATOR

Prenatal Period 0 IU; Postpartum Period 0 IU (placebo) Overall:The Prenatal Period will start at enrolment (17-24 weeks gestation) and last until delivery. The Postpartum Period will last from delivery until 6 months postpartum.

Dietary Supplement: Placebo

Group B

EXPERIMENTAL

Prenatal Period 4,200 IU/week of vitamin D3 (=600 IU/d); Postpartum Period 0 IU/week (placebo)

Dietary Supplement: Vitamin D3 (cholecalciferol); Dietary Supplement: Placebo

Group C

EXPERIMENTAL

Prenatal Period 16,800 IU/week of vitamin D3 (=2,400 IU/d); Postpartum Period 0 IU/week (placebo)

Dietary Supplement: Vitamin D3 (cholecalciferol); Dietary Supplement: Placebo

Group D

EXPERIMENTAL

Prenatal Period 28,000 IU/week of vitamin D3 (=4,000 IU/d); Postpartum Period 0 IU/week (placebo)

Dietary Supplement: Vitamin D3 (cholecalciferol); Dietary Supplement: Placebo

Group E

EXPERIMENTAL

Prenatal Period 28,000 IU/week of vitamin D3 (=4,000 IU/d); Postpartum Period 28,000 IU/week(=4,000 IU/d)

Dietary Supplement: Vitamin D3 (cholecalciferol)

Interventions

Vitamin D3 (cholecalciferol) DIETARY_SUPPLEMENT

The intervention is an oral tablet containing vitamin D3 (cholecalciferol). This vitamin D supplement will be provided in the form of small tablets (approximately 10 mm diameter) and will be custom- manufactured by Toronto Institute for Pharmaceutical Technology (TIPT) in Toronto, Ontario, Canada. Each weekly dose will consist of a single tablet. Across trial groups, the tablets will only vary with respect to the vitamin D3 dose, as described above.

Group B; Group C; Group D; Group E

Placebo DIETARY_SUPPLEMENT

This product will be identical in appearance, taste and texture to the experimental formulation but will not include any vitamin D3.

Group A; Group B; Group C; Group D

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women aged 18 years and above.
• Gestational age of 17 to 24 completed weeks estimated based on recalled last menstrual period (LMP) and/or ultrasound.
• Intends to permanently reside in the trial catchment area for at least 18 months.

You may not qualify if:

• History of medical conditions that may predispose the participant to vitamin D sensitivity, altered vitamin D metabolism and/or hypercalcemia, or history of renal calculi.
• High-risk pregnancy based on one or more of the following findings by point-of-care testing:
• Severe anemia: hemoglobin \<70 g/L assessed by Hemocue
• Moderate-severe proteinuria: ≥ 300 mg/dl (3+ or 4+) based on urine dipstick
• Hypertension: systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg
• Multiple gestation, major congenital anomaly, or severe oligohydramnios based on maternal history and/or ultrasound.
• Unwillingness to stop taking non-study vitamin D or calcium supplements or a multivitamin with calcium and/or vitamin D.
• Currently prescribed vitamin D supplements as part of a physician's treatment plan for vitamin D deficiency.
• Previous participation in the same study.

Sponsors & Collaborators

• The Hospital for Sick Children: lead
• International Centre for Diarrhoeal Disease Research, Bangladesh: collaborator
• Shimantik: collaborator
• Bill and Melinda Gates Foundation: collaborator

Study Sites (1)

International Centre for Diarrhoeal Disease Research, Bangladesh

Dhaka, Bangladesh

Location

Related Publications (8)

• Palacios C, Kostiuk LL, Cuthbert A, Weeks J. Vitamin D supplementation for women during pregnancy. Cochrane Database Syst Rev. 2024 Jul 30;7(7):CD008873. doi: 10.1002/14651858.CD008873.pub5.

  PMID: 39077939 DERIVED

• Pell LG, Ohuma EO, Yonemitsu C, Loutet MG, Ahmed T, Mahmud AA, Azad MB, Bode L, Roth DE. The Human-Milk Oligosaccharide Profile of Lactating Women in Dhaka, Bangladesh. Curr Dev Nutr. 2021 Nov 13;5(12):nzab137. doi: 10.1093/cdn/nzab137. eCollection 2021 Dec.

  PMID: 34993388 DERIVED

• O'Callaghan KM, Shanta SS, Fariha F, Harrington J, Mahmud AA, Emdin AL, Gernand AD, Ahmed T, Abrams SA, Moore DR, Roth DE. Effect of maternal prenatal and postpartum vitamin D supplementation on offspring bone mass and muscle strength in early childhood: follow-up of a randomized controlled trial. Am J Clin Nutr. 2022 Mar 4;115(3):770-780. doi: 10.1093/ajcn/nqab396.

  PMID: 34849536 DERIVED

• Jukic AMZ, Zuchniak A, Qamar H, Ahmed T, Mahmud AA, Roth DE. Vitamin D Treatment during Pregnancy and Maternal and Neonatal Cord Blood Metal Concentrations at Delivery: Results of a Randomized Controlled Trial in Bangladesh. Environ Health Perspect. 2020 Nov;128(11):117007. doi: 10.1289/EHP7265. Epub 2020 Nov 23.

  PMID: 33226277 DERIVED

• Subramanian A, Korsiak J, Murphy KE, Al Mahmud A, Roth DE, Gernand AD. Effect of vitamin D supplementation during pregnancy on mid-to-late gestational blood pressure in a randomized controlled trial in Bangladesh. J Hypertens. 2021 Jan;39(1):135-142. doi: 10.1097/HJH.0000000000002609.

  PMID: 32773651 DERIVED

• Jeong JH, Korsiak J, Papp E, Shi J, Gernand AD, Al Mahmud A, Roth DE. Determinants of Vitamin D Status of Women of Reproductive Age in Dhaka, Bangladesh: Insights from Husband-Wife Comparisons. Curr Dev Nutr. 2019 Oct 7;3(11):nzz112. doi: 10.1093/cdn/nzz112. eCollection 2019 Nov.

  PMID: 31723723 DERIVED

• Roth DE, Morris SK, Zlotkin S, Gernand AD, Ahmed T, Shanta SS, Papp E, Korsiak J, Shi J, Islam MM, Jahan I, Keya FK, Willan AR, Weksberg R, Mohsin M, Rahman QS, Shah PS, Murphy KE, Stimec J, Pell LG, Qamar H, Al Mahmud A. Vitamin D Supplementation in Pregnancy and Lactation and Infant Growth. N Engl J Med. 2018 Aug 9;379(6):535-546. doi: 10.1056/NEJMoa1800927.

  PMID: 30089075 DERIVED

• Roth DE, Gernand AD, Morris SK, Pezzack B, Islam MM, Dimitris MC, Shanta SS, Zlotkin SH, Willan AR, Ahmed T, Shah PS, Murphy KE, Weksberg R, Choufani S, Shah R, Al Mahmud A. Maternal vitamin D supplementation during pregnancy and lactation to promote infant growth in Dhaka, Bangladesh (MDIG trial): study protocol for a randomized controlled trial. Trials. 2015 Jul 14;16:300. doi: 10.1186/s13063-015-0825-8.

  PMID: 26169781 DERIVED

MeSH Terms

Interventions

Cholecalciferol

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Daniel Roth, MD

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 13, 2013
• First Posted: August 16, 2013
• Study Start: March 1, 2014
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2018
• Last Updated: August 31, 2018

Record last verified: 2018-08

Locations

BA (1)