Antenatal Vitamin D3 Dose-finding and Safety Study (AViDD-1)

Antenatal Vitamin D Supplementation to Improve Neonatal Health Outcomes in Dhaka, Bangladesh: Preliminary Dose-finding and Safety Study

This is a preliminary study of oral vitamin D3 supplementation in pregnant and non-pregnant women of reproductive age in Bangladesh. The primary objective of the study is to identify a dose of vitamin D3 that can safely be administered during pregnancy to improve the vitamin D status of the mother and infant.

Study Overview

• Status: Completed
• Conditions: Pregnancy; Nutritional Status; Vitamin D
• Intervention / Treatment: Dietary supplement: Vitamin D3; Dietary supplement: Vitamin D3; Dietary supplement: Vitamin D3

Detailed Description

Vitamin D deficiency is common among pregnant and non-pregnant Bangladeshi women. The consequences of vitamin D deficiency during pregnancy are unknown, but increasing evidence suggests it may compromise fetal growth and development of the immune system. We hypothesize that vitamin D deficiency in pregnant women has an adverse effect on the newborn's defenses against infectious diseases in early infancy, and thus contributes to the high rates of neonatal mortality in South Asia. Randomized controlled trials of antenatal vitamin D supplementation are needed to test this hypothesis. However, preliminary studies are first necessary to establish a safe and efficacious dose of vitamin D to be used in such trials. In the proposed study, we will measure the response of the 25-hydroxyvitamin D serum concentration (a biomarker of vitamin D status) to oral vitamin D3 supplementation in pregnant women and non-pregnant women of reproductive age. The goal is to establish a safe, efficacious and feasible weekly vitamin D supplementation regimen for use in future trials. Five groups of approximately 15 women (3 groups of pregnant and 2 groups of non-pregnant women; total up to 75 women) will be supplemented and followed closely for 10 weeks (non-pregnant women) or until delivery (pregnant participants). The primary outcomes will be the change in 25-hydroxyvitamin D concentrations following vitamin D supplementation, and safety parameters that reflect calcium regulation (serum albumin-adjusted calcium concentrations and urine calcium excretion) and fetal development.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 1

Contacts and Locations

Study Locations

• Bangladesh
  • Dhaka, Bangladesh
    • SHIMANTIK Maternity Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 34 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Healthy women, age 18 to < 35 years, who are clients at the Shimantik clinic or friends/relatives of Shimantik clients.
• Current permanent residence in Dhaka at a fixed address, and have plans to stay in Dhaka for at least 4 months.
• Pregnant women: Enrolled between 26th and 30th week of gestation (participants enrolled in 26th week will not start on-study until the 27th week or later), with a normal medical and obstetric history. Gestational age will be estimated based on the first day of the last menstrual period (LMP).
• Informed consent provided after having an opportunity to consult with husband and/or family members.

Exclusion Criteria:

• Current self-reported use of any non-food-based dietary supplements containing vitamin D (i.e., commercial micronutrient pills or capsules containing vitamin D).
• Current use of anti-convulsant or anti-mycobacterial (tuberculosis) medications.
• Severe anemia (hemoglobin concentration < 70 g/L).
• Hypertension (systolic blood pressure >= 140 mmHg or diastolic blood pressure >= 90 mmHg on at least two measurements).
• In pregnant women: previous history of giving birth to an infant with congenital anomalies.
• In non-pregnant women: currently breast-feeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A1 - non-pregnant single-dose	Dietary supplement: Vitamin D3; Vitamin D3 oral liquid 70,000 IU once; Other Names: Cholecalciferol; Vigantol Oil; Dietary supplement: Vitamin D3; Vitamin D3 oral liquid 70,000 IU as loading dose, then 35,000 IU weekly thereafter for 10 weeks (non-pregnant) or until delivery (pregnant); Other Names: Cholecalciferol; Vigantol Oil; Dietary supplement: Vitamin D3; Vitamin D3 14,000 IU per week by mouth, starting at 27-30 weeks gestation and continued until delivery.; Other Names: Cholecalciferol; Vigantol Oil
Experimental: A2 - non-pregnant; weekly dose	Dietary supplement: Vitamin D3; Vitamin D3 oral liquid 70,000 IU once; Other Names: Cholecalciferol; Vigantol Oil; Dietary supplement: Vitamin D3; Vitamin D3 oral liquid 70,000 IU as loading dose, then 35,000 IU weekly thereafter for 10 weeks (non-pregnant) or until delivery (pregnant); Other Names: Cholecalciferol; Vigantol Oil; Dietary supplement: Vitamin D3; Vitamin D3 14,000 IU per week by mouth, starting at 27-30 weeks gestation and continued until delivery.; Other Names: Cholecalciferol; Vigantol Oil
Experimental: B1 - pregnant; single-dose	Dietary supplement: Vitamin D3; Vitamin D3 oral liquid 70,000 IU once; Other Names: Cholecalciferol; Vigantol Oil; Dietary supplement: Vitamin D3; Vitamin D3 oral liquid 70,000 IU as loading dose, then 35,000 IU weekly thereafter for 10 weeks (non-pregnant) or until delivery (pregnant); Other Names: Cholecalciferol; Vigantol Oil; Dietary supplement: Vitamin D3; Vitamin D3 14,000 IU per week by mouth, starting at 27-30 weeks gestation and continued until delivery.; Other Names: Cholecalciferol; Vigantol Oil
Experimental: B2 - pregnant; weekly dose	Dietary supplement: Vitamin D3; Vitamin D3 oral liquid 70,000 IU once; Other Names: Cholecalciferol; Vigantol Oil; Dietary supplement: Vitamin D3; Vitamin D3 oral liquid 70,000 IU as loading dose, then 35,000 IU weekly thereafter for 10 weeks (non-pregnant) or until delivery (pregnant); Other Names: Cholecalciferol; Vigantol Oil; Dietary supplement: Vitamin D3; Vitamin D3 14,000 IU per week by mouth, starting at 27-30 weeks gestation and continued until delivery.; Other Names: Cholecalciferol; Vigantol Oil
Active Comparator: C1 - active control; pregnant women	Dietary supplement: Vitamin D3; Vitamin D3 oral liquid 70,000 IU once; Other Names: Cholecalciferol; Vigantol Oil; Dietary supplement: Vitamin D3; Vitamin D3 oral liquid 70,000 IU as loading dose, then 35,000 IU weekly thereafter for 10 weeks (non-pregnant) or until delivery (pregnant); Other Names: Cholecalciferol; Vigantol Oil; Dietary supplement: Vitamin D3; Vitamin D3 14,000 IU per week by mouth, starting at 27-30 weeks gestation and continued until delivery.; Other Names: Cholecalciferol; Vigantol Oil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
25-hydroxyvitamin D concentration	6 scheduled timepoints during supplementation period
Serum calcium concentration (albumin-corrected)	6 scheduled timepoints during supplementation period
Urine calcium: creatinine ratio	7-8 scheduled timepoints during supplementation period

Secondary Outcome Measures

Outcome Measure	Time Frame
Blood pressure	Weekly during supplementation period
Urinary protein excretion	Weekly during supplementation period
Maternal weight	Weekly during supplementation period
Birth anthropometry	At birth
Neonatal echocardiography	Neonatal period
Fetal LL-37 expression/secretion in saliva, vernix, and cord tissue	Birth

Collaborators and Investigators

• Sponsor: Johns Hopkins Bloomberg School of Public Health
• Collaborators: Johns Hopkins University
• Investigators: Principal Investigator: Rubhana Raqib, PhD, International Centre for Diarrhoeal Disease Research, Bangladesh; Principal Investigator: Abdullah Baqui, MBBS, The Johns Hopkins Bloomberg School of Public Health; Principal Investigator: Shams El Arifeen, MBBS, International Centre for Diarrhoeal Disease Research, Bangladesh; Study Director: Daniel E Roth, MD, The Johns Hopkins Bloomberg School of Public Health

Publications and helpful links

General Publications

• Islam MZ, Lamberg-Allardt C, Karkkainen M, Outila T, Salamatullah Q, Shamim AA. Vitamin D deficiency: a concern in premenopausal Bangladeshi women of two socio-economic groups in rural and urban region. Eur J Clin Nutr. 2002 Jan;56(1):51-6. doi: 10.1038/sj.ejcn.1601284.
• Islam MZ, Shamim AA, Kemi V, Nevanlinna A, Akhtaruzzaman M, Laaksonen M, Jehan AH, Jahan K, Khan HU, Lamberg-Allardt C. Vitamin D deficiency and low bone status in adult female garment factory workers in Bangladesh. Br J Nutr. 2008 Jun;99(6):1322-9. doi: 10.1017/S0007114508894445.
• Roth DE, Al Mahmud A, Raqib R, Black RE, Baqui AH. Pharmacokinetics of a single oral dose of vitamin D3 (70,000 IU) in pregnant and non-pregnant women. Nutr J. 2012 Dec 27;11:114. doi: 10.1186/1475-2891-11-114.

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: July 13, 2009
• First Submitted That Met QC Criteria: July 13, 2009
• First Posted (Estimate): July 14, 2009

Study Record Updates

• Last Update Posted (Estimate): August 17, 2012
• Last Update Submitted That Met QC Criteria: August 16, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: safety; pharmacokinetics
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: JHU-1819