Micronutrient Dose Response Study in Bangladesh

Not Applicable

Active, not recruiting

• Conditions: Micronutrient Status
• Interventions: Dietary Supplement: Micronutrient Supplement

• Registration Number: NCT06081114
• Lead Sponsor: Johns Hopkins Bloomberg School of Public Health

Brief Summary

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.

Detailed Description

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 Timeline

• Study First Submitted: 2023-09-21
• Study First Submitted QC: 2023-10-09
• Study First Posted: 2023-10-13
• Study Start: 2023-10-22
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-29
• Last Update Posted: 2025-05-02
• Primary Completion: 2025-09-30
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 650

Inclusion Criteria

Either

• Women (non-pregnant and non-lactating) and not planning a pregnancy in the next 6 months

OR

• Pregnant women (gestational age at enrollment of 12-14 weeks)

Exclusion Criteria

• Eligible women not consenting to participate
• Based on point-of-care clinical indicators after enrollment and prior to starting the intervention that is indicative of pre-existing liver or kidney conditions and severe anemia

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MNs - Level 3	Micronutrient Supplement	Dose 3 of micronutrients listed below provided daily in the form of a powdered drink. Micronutrients: Vitamin A - 1.48 mg Vitamin D - 0.06 mg Vitamin E - 184 mg Vitamin B1 - 4.2 mg Vitamin B2 - 4.2 mg Vitamin B3 - 82 mg Vitamin B6 - 8.1 mg Vitamin B12 - 0.0154 mg Vitamin C - 20 mg Iron - 10 mg Zinc - 5 mg Selenium - 0.235 mg Choline - 900 mg Pantothenic acid - 7mg Biotin - 0.035 mg Potassium - 1000 mg Manganese - 2.6 mg Magnesium - 145 mg Plus, a daily fortified balanced energy and protein food supplement containing 400 kcals and 14 g of protein and 1 RDA of 18 micronutrients will be given daily including 90 ug of vitamin K, 400 ug of folic acid, 1 mg of copper and 500 mg of calcium
MNs - Placebo	Micronutrient Supplement	Placebo powder, daily in the form of a powdered flavored drink. Plus, a daily fortified balanced energy and protein food supplement containing 400 kcals and 14 g of protein and 1 recommended daily allowance (RDA) of 18 micronutrients will be given daily including 90 ug of vitamin K, 400 ug of folic acid, 1 mg of copper and 500 mg of calcium
MNs - Level 2	Micronutrient Supplement	Dose 2 of micronutrients listed below provided daily in the form of a powdered flavored drink. Micronutrients: Vitamin A -0.93 mg Vitamin D - 0.04 mg Vitamin E - 109 mg Vitamin B1 - 2.8 mg Vitamin B2 - 2.8 mg Vitamin B3 - 47 mg Vitamin B6 - 4.1 mg Vitamin B12 - 0.0094 mg Vitamin C - 20 mg Iron - 10 mg Zinc - 5 mg Selenium - 0.135 mg Choline - 750 mg Pantothenic acid - 7mg Biotin - 0.035 mg Potassium - 1000 mg Manganese - 2.6 mg Magnesium - 145 mg Plus, a daily fortified balanced energy and protein food supplement containing 400 kcals and 14 g of protein and 1 RDA of 18 micronutrients will be given daily including 90 ug of vitamin K, 400 ug of folic acid, 1 mg of copper and 500 mg of calcium
MNs - Level 1	Micronutrient Supplement	Dose 1 of micronutrients (MNs) listed provided daily in the form of a powdered drink. Micronutrients: Vitamin A -0.355 mg Vitamin D - 0.02 mg Vitamin E - 34 mg Vitamin B1 - 1.4 mg Vitamin B2 - 1.4 mg Vitamin B3 - 17 mg Vitamin B6 - 2.1 mg Vitamin B12 - 0.0034 mg Vitamin C - 20 mg Selenium - 0.035 mg Choline - 550 mg Pantothenic acid - 7mg Biotin - 0.035 mg Potassium - 1000 mg Manganese - 2.6 mg Magnesium - 145 mg Plus, a daily fortified balanced energy and protein supplement containing 400 kcals and 14 g of protein and 1 RDA of 18 micronutrients will be given simultaneously including 90 ug of vitamin K, 400 ug of folic acid, 1 mg of Copper and 500 mg of calcium

Primary Outcome Measures

Name	Time	Method
Change in vitamin D status	Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)	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.
Change in B-vitamin static indicators	Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)	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.
Change in B-vitamin enzymatic activity	Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)	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.
Change in vitamin A status	Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)	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.
Change in iron status	Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)	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.
Change in vitamin E status	Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)	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.
Change in iodine status	Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)	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.
Change in selenium static indicator	Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)	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.
Change in selenium enzymatic indicator	Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)	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.
Change in zinc status	Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)	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.

Secondary Outcome Measures

Name	Time	Method
Changes in inflammation	Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)	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.
Change in hormonal markers	Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)	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.
Change in clinical markers of liver enzymes	Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)	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.
Change in clinical markers of electrolytes	Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)	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.
Change in clinical markers of lipid profile	Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)	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.
Change in clinical markers of renal function	Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)	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.
Change in glucose	Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)	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.
Change in hemoglobin	Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)	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.
Change in serum minerals	Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)	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.
Change in bone turnover biomarker	Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)	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.
Change in urinary metabolite of vitamin E	Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)	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.

Trial Locations

Locations (1)

JiVitA Project; 🇧🇩 Rangpur, Bangladesh