Clinical trial NCT00938600: Antenatal Vitamin D3 Dose-finding and Safety Study
Official title: Antenatal Vitamin D Supplementation to Improve Neonatal Health Outcomes in Dhaka, Bangladesh: Preliminary Dose-finding and Safety Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pregnancy
Nutritional Status
Vitamin D
Keywords: pharmacokinetics
safety
Lead sponsor: Johns Hopkins Bloomberg School of Public Health
Sponsor class: OTHER
Collaborators: name: Johns Hopkins University
First posted: 2009-07-14
Enrollment: 75
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 34
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 25-hydroxyvitamin D concentration
timeFrame: 6 scheduled timepoints during supplementation period
measure: Serum calcium concentration (albumin-corrected)
timeFrame: 6 scheduled timepoints during supplementation period
measure: Urine calcium: creatinine ratio
timeFrame: 7-8 scheduled timepoints during supplementation period
Secondary outcomes:
measure: Blood pressure
timeFrame: Weekly during supplementation period
measure: Urinary protein excretion
timeFrame: Weekly during supplementation period
measure: Maternal weight
timeFrame: Weekly during supplementation period
measure: Birth anthropometry
timeFrame: At birth
measure: Neonatal echocardiography
timeFrame: Neonatal period
measure: Fetal LL-37 expression/secretion in saliva, vernix, and cord tissue
timeFrame: Birth
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: SHIMANTIK Maternity Centre
Study officials:
affiliation: The Johns Hopkins Bloomberg School of Public Health
name: Abdullah Baqui, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh
name: Rubhana Raqib, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh
name: Shams El Arifeen, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: The Johns Hopkins Bloomberg School of Public Health
name: Daniel E Roth, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.