Micronutrient Dose Response Study in Bangladesh

NCT06081114 | Active Not Recruiting DMC

• 2 other identifiers: INV-033628IRB00022171
• Study Type: interventional
• Target: 643
• Locations: 1 country
• Sites: 1

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.

Conditions

Micronutrient Status

Keywords

Pregnancy; Micronutrients; Energy; Supplements; Biochemical indicators; protein

Outcome Measures

Primary Outcomes (10)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  Baseline, midline, end-line, up to 1 month post-partum (Pregnant women). Baseline, midline, end-line, up to 3 months (non-pregnant women)

Secondary Outcomes (11)

• 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)

• 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)

• 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)

• 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)

• 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)

Other Outcomes (16)

• Number of participants with side effects

  Weekly from enrollment up to 1 month postpartum for pregnant women. Weekly from enrollment up to 3 months for non-pregnant women

• Breastmilk Vitamin A concentration

  1 month postpartum

• Breastmilk Vitamin E concentration

  1 month postpartum

Study Arms (4)

MNs - Placebo

PLACEBO COMPARATOR

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

Dietary Supplement: Micronutrient Supplement

MNs - Level 1

ACTIVE COMPARATOR

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

Dietary Supplement: Micronutrient Supplement

MNs - Level 2

ACTIVE COMPARATOR

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

Dietary Supplement: Micronutrient Supplement

MNs - Level 3

ACTIVE COMPARATOR

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

Dietary Supplement: Micronutrient Supplement

Interventions

Micronutrient Supplement DIETARY_SUPPLEMENT

A packaged food supplement providing calories and protein and fortified with micronutrients provided at an approximate RDA.

Also known as: Balanced Energy and Protein Supplement (BEP)

MNs - Level 1; MNs - Level 2; MNs - Level 3; MNs - Placebo

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Either
• Women (non-pregnant and non-lactating) and not planning a pregnancy in the next 6 months
• Pregnant women (gestational age at enrollment of 12-14 weeks)

You may not qualify if:

• 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

Sponsors & Collaborators

• Johns Hopkins Bloomberg School of Public Health: lead
• International Center for Diarrheal Disease Research, Bangladesh (icddr,b): collaborator
• Bill and Melinda Gates Foundation: collaborator

Study Sites (1)

JiVitA Project

Rangpur City, Bangladesh

Location

Related Publications (1)

• Siddiqua TJ, Schulze KJ, Hasan ST, Ahsan KB, Bandyopadhyay S, Zavala E, Ali H, Haque R, Sujan HM, Rahman MH, Baker S, Stephenson KK, Ge X, Gough EK, Langevin B, Wu LSF, Dyer B, Roy AK, Jubair M, Nishan AA, Rosenblum M, Gopalakrishnan M, Kraemer K, Erchick DJ, Ahmed T, Christian P. Micronutrient dose response (MiNDR) study among women of reproductive age and pregnant women in rural Bangladesh: study protocol for double-blind, randomised, controlled trials. BMJ Open. 2025 Jan 4;15(1):e090108. doi: 10.1136/bmjopen-2024-090108.

  PMID: 39755576 DERIVED

Related Links

• Trial protocol

Study Officials

• Parul Chrisian, DrPH

  Johns Hopkins Bloomberg School of Public Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2023
• First Posted: October 13, 2023
• Study Start: October 22, 2023
• Primary Completion: September 22, 2025
• Study Completion (Estimated): September 30, 2026
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

BA (1)