Antenatal Vitamin D3 Dose-finding and Safety Study

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Vitamin D, Pregnancy, Nutritional Status

Intervention / Treatment
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* Dietary Supplement: Vitamin D3
* Dietary Supplement: Vitamin D3
* Dietary Supplement: Vitamin D3


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 34 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A1 - non-pregnant single-dose<br> | Dietary Supplement: Vitamin D3<br>* Vitamin D3 oral liquid 70,000 IU once<br>* Other names: Vigantol Oil;|
| Experimental: A2 - non-pregnant; weekly dose<br> | Dietary Supplement: Vitamin D3<br>* 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)<br>* Other names: Vigantol Oil;|
| Experimental: B1 - pregnant; single-dose<br> | Dietary Supplement: Vitamin D3<br>* Vitamin D3 oral liquid 70,000 IU once<br>* Other names: Vigantol Oil;|
| Experimental: B2 - pregnant; weekly dose<br> | Dietary Supplement: Vitamin D3<br>* 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)<br>* Other names: Vigantol Oil;|
| Active Comparator: C1 - active control; pregnant women<br> | Dietary Supplement: Vitamin D3<br>* Vitamin D3 14,000 IU per week by mouth, starting at 27-30 weeks gestation and continued until delivery.<br>* Other names: Vigantol Oil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacokinetics, safety