The recommended daily amounts of vitamins and minerals, referred to as micronutrients, are based on data from high income settings and for healthy populations do not fully correct nutritional deficiencies in undernourished settings. This study will determine the minimum acceptable doses across a range of nutrients at which sufficiency is achieved with supplementation using biochemical indicators of nutritional status in non-pregnant (non-lactating) women of reproductive age and pregnant women in Bangladesh. In this double-masked randomized controlled trial, a dose response study will be undertaken using increasing levels of doses provided as supplements to women (pregnant or non-pregnant) with nutritional indicators as outcomes.
The primary aims of the study are to: 1. To characterize the time-course of in vivo exposures (dose response) of several micronutrients in pregnant and non-pregnant and non-lactating women of reproductive age (WRA) in a real-life situation. 2. To characterize any clinically meaningful prognostic factors that can explain the between-subject variability. 3. To investigate whether the micronutrients follow dose-proportional pharmacokinetics.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
643
A packaged food supplement providing calories and protein and fortified with micronutrients provided at an approximate RDA.
JiVitA Project
Rangpur City, Bangladesh
Change in vitamin A status
Plasma retinol (μmol/L), retinyl esters (μmol/L), and serum retinol binding protein (μmol/L) For women in reproductive age, these biomarkers will be measured at baseline, midline (1.5 months), and end-line (3 months). For pregnant women, the biomarkers will be measured at baseline (10-12 weeks of gestation), mid-pregnancy (22 weeks or 30 weeks of gestation), late pregnancy (36 weeks of gestation), and 1 month postpartum.
Time frame: Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)
Change in vitamin D status
Serum 25(hydroxy)D (nmol/L) For women in reproductive age, these biomarkers will be measured at baseline, midline (1.5 months), and end-line (3 months). For pregnant women, the biomarkers will be measured at baseline (10-12 weeks of gestation), mid-pregnancy (22 weeks or 30 weeks of gestation), late pregnancy (36 weeks of gestation), and 1 month postpartum.
Time frame: Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)
Change in vitamin E status
Plasma α and γ tocopherol (μmol/L) For women in reproductive age, these biomarkers will be measured at baseline, midline (1.5 months), and end-line (3 months). For pregnant women, the biomarkers will be measured at baseline (10-12 weeks of gestation), mid-pregnancy (22 weeks or 30 weeks of gestation), late pregnancy (36 weeks of gestation), and 1 month postpartum.
Time frame: Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)
Change in B-vitamin static indicators
Vitamin B12 (plasma homocysteine, methylmalonic acid, and holo-transcobalamin, and serum B12); Folic acid (serum folate, and whole blood folate); Vitamin B1 (urinary B1 excretion), Vitamin B2 (urinary B2 excretion), Vitamin B3 (urinary N-methylnicotinamide and 2-pyridone), Vitamin B6 (plasma pyridoxal 5' phosphate and other B6 vitamers, urinary B6 excretion). All the indicators will be expressed as pg/ml. For women in reproductive age, these biomarkers will be measured at baseline, midline (1.5 months), and end-line (3 months). For pregnant women, the biomarkers will be measured at baseline (10-12 weeks of gestation), mid-pregnancy (22 weeks or 30 weeks of gestation), late pregnancy (36 weeks of gestation), and 1 month postpartum.
Time frame: Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)
Change in B-vitamin enzymatic activity
Vitamin B1 (erythrocyte transketolase activity), Vitamin B2 (erythrocyte Glutathione reductase activity, urinary B2 excretion), Vitamin B3 (erythrocyte nicotinamide adenine dinucleotide (NAD) and NAD/nicotinamide-adenine dinucleotide phosphate (NADP) ratio. All the indicators will be presented as ratio or activity coefficient. For women in reproductive age, these biomarkers will be measured at baseline, midline (1.5 months), and end-line (3 months). For pregnant women, the biomarkers will be measured at baseline (10-12 weeks of gestation), mid-pregnancy (22 weeks or 30 weeks of gestation), late pregnancy (36 weeks of gestation), and 1 month postpartum.
Time frame: Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)
Change in iron status
Serum ferritin and soluble transferrin receptor (μg/L) For women in reproductive age, these biomarkers will be measured at baseline, midline (1.5 months), and end-line (3 months). For pregnant women, the biomarkers will be measured at baseline (10-12 weeks of gestation), mid-pregnancy (22 weeks or 30 weeks of gestation), late pregnancy (36 weeks of gestation), and 1 month postpartum.
Time frame: Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)
Change in iodine status
Urinary iodine (μg/L), and thyroglobulin (μg/L) For women in reproductive age, these biomarkers will be measured at baseline, midline (1.5 months), and end-line (3 months). For pregnant women, the biomarkers will be measured at baseline (10-12 weeks of gestation), mid-pregnancy (22 weeks or 30 weeks of gestation), late pregnancy (36 weeks of gestation), and 1 month postpartum.
Time frame: Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)
Change in selenium static indicator
Serum selenium (μg/L) For women in reproductive age, these biomarkers will be measured at baseline, midline (1.5 months), and end-line (3 months). For pregnant women, the biomarkers will be measured at baseline (10-12 weeks of gestation), mid-pregnancy (22 weeks or 30 weeks of gestation), late pregnancy (36 weeks of gestation), and 1 month postpartum.
Time frame: Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)
Change in selenium enzymatic indicator
Plasma Glutathione peroxidase-3 (U/L) For women in reproductive age, these biomarkers will be measured at baseline, midline (1.5 months), and end-line (3 months). For pregnant women, the biomarkers will be measured at baseline (10-12 weeks of gestation), mid-pregnancy (22 weeks or 30 weeks of gestation), late pregnancy (36 weeks of gestation), and 1 month postpartum.
Time frame: Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)
Change in zinc status
Serum Zinc (μg/L) For women in reproductive age, these biomarkers will be measured at baseline, midline (1.5 months), and end-line (3 months). For pregnant women, the biomarkers will be measured at baseline (10-12 weeks of gestation), mid-pregnancy (22 weeks or 30 weeks of gestation), late pregnancy (36 weeks of gestation), and 1 month postpartum.
Time frame: Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)
Changes in inflammation
Serum Alpha glycoprotein (AGP) and plasma C-reactive protein (CRP). These will be expressed as mg/L. For women in reproductive age, these biomarkers will be measured at baseline, midline (1.5 months), and end-line (3 months). For pregnant women, the biomarkers will be measured at baseline (10-12 weeks of gestation), mid-pregnancy (22 weeks or 30 weeks of gestation), late pregnancy (36 weeks of gestation), and 1 month postpartum.
Time frame: Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)
Change in hormonal markers
Plasma hepcidin (μg/L), erythropoietin (μg/L), and serum parathyroid hormone (μg/L) For women in reproductive age, these biomarkers will be measured at baseline, midline (1.5 months), and end-line (3 months). For pregnant women, the biomarkers will be measured at baseline (10-12 weeks of gestation), mid-pregnancy (22 weeks or 30 weeks of gestation), late pregnancy (36 weeks of gestation), and 1 month postpartum.
Time frame: Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)
Change in clinical markers of liver enzymes
Plasma alanine transaminase (U/L), and Aspartate aminotransferase (U/L) For women in reproductive age, these biomarkers will be measured at baseline, midline (1.5 months), and end-line (3 months). For pregnant women, the biomarkers will be measured at baseline (10-12 weeks of gestation), mid-pregnancy (22 weeks or 30 weeks of gestation), late pregnancy (36 weeks of gestation), and 1 month postpartum.
Time frame: Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)
Change in clinical markers of lipid profile
Plasma triglyceride, total cholesterol, high density lipoprotein, low density lipoprotein. These will be expressed as mg/dL. For women in reproductive age, these biomarkers will be measured at baseline, midline (1.5 months), and end-line (3 months). For pregnant women, the biomarkers will be measured at baseline (10-12 weeks of gestation), mid-pregnancy (22 weeks or 30 weeks of gestation), late pregnancy (36 weeks of gestation), and 1 month postpartum.
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Time frame: Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)
Change in clinical markers of renal function
Plasma creatinine (mg/dL), and blood urea nitrogen (mg/dL) For women in reproductive age, these biomarkers will be measured at baseline, midline (1.5 months), and end-line (3 months). For pregnant women, the biomarkers will be measured at baseline (10-12 weeks of gestation), mid-pregnancy (22 weeks or 30 weeks of gestation), late pregnancy (36 weeks of gestation), and 1 month postpartum.
Time frame: Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)
Change in clinical markers of electrolytes
Plasma sodium, calcium, potassium, and chloride. These will be expressed as mmol/L. For women in reproductive age, these biomarkers will be measured at baseline, midline (1.5 months), and end-line (3 months). For pregnant women, the biomarkers will be measured at baseline (10-12 weeks of gestation), mid-pregnancy (22 weeks or 30 weeks of gestation), late pregnancy (36 weeks of gestation), and 1 month postpartum.
Time frame: Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)
Change in glucose
Plasma glucose (mg/dL) For women in reproductive age, these biomarkers will be measured at baseline, midline (1.5 months), and end-line (3 months). For pregnant women, the biomarkers will be measured at baseline (10-12 weeks of gestation), mid-pregnancy (22 weeks or 30 weeks of gestation), late pregnancy (36 weeks of gestation), and 1 month postpartum.
Time frame: Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)
Change in hemoglobin
Whole blood hemoglobin (g/L) For women in reproductive age, these biomarkers will be measured at baseline, midline (1.5 months), and end-line (3 months). For pregnant women, the biomarkers will be measured at baseline (10-12 weeks of gestation), mid-pregnancy (22 weeks or 30 weeks of gestation), late pregnancy (36 weeks of gestation), and 1 month postpartum.
Time frame: Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)
Change in serum minerals
Serum copper, manganese, magnesium, phosphorus, and iron. These will be expressed as μg/L. For women in reproductive age, these biomarkers will be measured at baseline, midline (1.5 months), and end-line (3 months). For pregnant women, the biomarkers will be measured at baseline (10-12 weeks of gestation), mid-pregnancy (22 weeks or 30 weeks of gestation), late pregnancy (36 weeks of gestation), and 1 month postpartum.
Time frame: Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)
Change in bone turnover biomarker
Pyrilinks-D urine test (nmol/L) For women in reproductive age, these biomarkers will be measured at baseline, midline (1.5 months), and end-line (3 months). For pregnant women, the biomarkers will be measured at baseline (10-12 weeks of gestation), mid-pregnancy (22 weeks or 30 weeks of gestation), late pregnancy (36 weeks of gestation), and 1 month postpartum.
Time frame: Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)
Change in urinary metabolite of vitamin E
Urinary alpha-carboxy ethyl hydroxy chromanol (nmol/L) will be measured only in pregnancy. For pregnant women, the biomarkers will be measured at baseline (10-12 weeks of gestation), mid-pregnancy (22 weeks or 30 weeks of gestation), late pregnancy (36 weeks of gestation), and 1 month postpartum.
Time frame: Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)