Blood Pressure, Body Composition, Bone Mineral Density, HRQOL (Health Related Quality Of Life), Linear Growth, Micronutrient Status, Neurodevelopment Outcome, Stunting, Underweight, Waist-to-height Ratio
Conditions
Brief summary
MEDHA is a randomized controlled trial among 10-18 year old girls to examine the use-case of the United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP) multiple micronutrient supplement (MMS) formulation and to test an enhanced regimen (MMS+) with additional nutrients, vs. weekly iron-folic acid as standard of care on outcomes of neurodevelopment, linear growth, biochemical status, bone health, and other functional and health outcomes. This study is an individually randomized, open-label, three-arm trial of 3,000 participants supplemented for 12 months to assess the efficacy and safety of nutrient supplementation. Results of the study will inform the design of nutritional interventions and policy for this age group. In the context of the trial, the investigators will also do in-depth clinical and health assessments and collect biospecimens for a bio-archive for future deep-phenotyping of this population. This study will be conducted at the Johns Hopkins Bangladesh JiVitA field site in rural Gaibandha District of Bangladesh.
Detailed description
Adolescents (10-19 year olds) are an understudied group despite increasing numbers in many regions, especially in low- and middle-income countries (LMICs). Numerous reviews on adolescent health and nutrition have identified major data gaps for this population, including lack of information on the nutritional challenges and the burden of existing deficiencies adolescents face and uncertainty about the level of nutritional support required during this period of rapid physical and cognitive development during and following puberty. The consequences of poor adolescent nutrition for reproductive health and survival as well as bone health in later life among females calls for special attention to vulnerable girls in LMICs. The primary aim of this study is to determine the efficacy of daily supplementation with MMS (using the UNIMMAP formulation) and an enhanced regimen (MMS+) composed of UNIMMAP plus additional nutrients (calcium, choline, docosahexaenoic acid -DHA, and higher amount of vitamin D) vs. weekly iron-folic acid (IFA) alone on a range of neurodevelopment, biochemical, linear growth and functional outcomes among 10-18 year old girls in rural Bangladesh. The investigators hypothesize that daily MMS or MMS+ will result in an improvement for the co-primary outcomes of school achievement and physical growth (HAZ), and secondary functional outcomes including neurocognitive function, bone health, and biochemical nutrient status among adolescents following 6 and 12 months of supplementation compared with weekly IFA supplementation.
Interventions
DIETARY_SUPPLEMENTIron (60 mg)- folic acid (400 ug) [IFA]
Weekly IFA will be provided in the control arm as standard-of-care for a year
DIETARY_SUPPLEMENTMultiple micronutrient supplement [MMS]
Experimental: Multiple micronutrient supplement \[MMS\] A daily MMS supplement containing 15 micronutrients using the UNIMMAP (United Nations International Multiple Micronutrient Antenatal Preparation) formulation. This will be provided in a daily tablet form for a year.
DIETARY_SUPPLEMENTMultiple micronutrient supplement Plus [MMS+]
Experimental: Multiple micronutrient supplement Plus \[MMS+\] MMS+ will be a package of nutrient supplements comprising the UNIMMAP tablet, plus a lipid-based chickpea product with choline, calcium and additional vitamin D, plus a local DHA/EPA softgel taken daily for a year.
Sponsors
Johns Hopkins Bloomberg School of Public Health
International Centre for Diarrhoeal Disease Research, Bangladesh
Bill and Melinda Gates Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Masking description
Given the nature of the three types of interventions, and their taste and the regimen, and difficulty in creation of true placebos, this trial will not be masked. Those providing the intervention will be a cadre of community workers separate from the data collection teams.
Eligibility
Sex/Gender
FEMALE
Age
10 Years to 18 Years
Healthy volunteers
Yes
Inclusion criteria
* Unmarried 10-18 year old females * living in their parental home in the study area
Exclusion criteria
* Married females under 18 years old; * those with a history or diagnosis of chronic or congenital heart disease, chronic kidney or lung disease, cancer, and epilepsy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Height-for-age Z score | Baseline (pre-supplementation) and at the midline (6 months) and endline (12 months) visits | Height will be assessed and expressed as a Z-score using reference standards for children. Stunting will be defined using HAZ \< -2. |
| Wide Range Achievement Test (WRAT-5) Composite Score | Baseline (pre-supplementation) and at midline (6 months) and endline (12 month) visits. | The Wide Range Achievement Test assess reading, writing and arithmetic and is a school achievement test. The total score on this test will be used. The mean for the total composite score is 100 and SD is 15. Most scores fall between 70 and 130, with higher scores indicating above-average achievement and lower scores indicating below-average achievement |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| General Intelligence as assessed by the Wechsler Abbreviated Scale of Intelligence (WASI-II) | Baseline (presupplementation) and endline (12 months) | This will be assessed using Wechsler Abbreviated Scale of Intelligence (WASI-II). The full scale IQ has a mean (SD) of 75 (12). |
| Executive function as assessed by Word Span | Baseline and Endline (12months) | Assessed using Word Span |
| Executive function as assessed by Dimensional Card Change Sort | Baseline and Endline (12months) | Assessed using Dimensional Card Change Sort (DCCS) |
| Motor function standardized score as assessed by Movement Assessment Batter for Children - 3 | Baseline and endline (12months) | Using Movement Assessment Battery for Children -3. Standardized scores for Pegboard, Manual Dexterity, and Balance will be used. Task scores have a mean (SD) of 10(3). |
| Bone mineral density | Baseline and Endline (12 months) | Radiography of radius and tibia |
| Body mass index Z-score | At Baseline (pre-supplementation), midline (6 months) and 12 (months) | BMIZ score will be derived using weight and height measurements using reference standards. BMIZ \< 2 is used to define underweight. |
| Nutrient status | Baseline (pre-supplementation) and Midline (6 months) | Assessed using blood serum/plasma, or urine (vitamin A, D, E, B12, zinc, Hb, iodine, Thyroglobulin) |
| Endocrine factors | Baseline (pre-supplementation) and midline (6 months) | Leptin, Estradiol, Osteocalcin |
| Health-related Quality of Life (HRQoL) | At baseline and endline (12 months) | The HRQoL; (EQ-5D-5L) will be used. |
| Blood Pressure (mmHg) | Baseline (pre-supplementation), midline (6 months) and endline (12 months) | Blood pressure - systolic and diastolic BP (mm Hg) taken using a BP monitor. |
| % Fat free mass | Baseline (presupplementation), midline (6 months) and endline (12 months) | Body composition will be assessed using anthropometry and skinfold measurements |
| Waist-to-Height Ratio | Baseline (presupplementation), midline (6months) and endline (12 months) | Waist circumference and height will be assessed to derive this ratio |
| Hand grip strength | Baseline (presupplementation), midline (6months), endline (12 months) | Using kg pressure |
| Conners Parent Rating Scale Scores | Baseline and Endline (12 months) | These standardized scales will be administered to assess behavioral disorders among children. |
| WRAT-5 math, reading and spelling scores | Baseline, midline (6 months) and endline (12 months) | Individual domain scores derived from the WRAT-5. The mean for each is approximately 70 with SD of 20. |
Countries
Bangladesh
Contacts
CONTACTParul Christian, DrPH
CONTACTDaniel Erchick, PhD
PRINCIPAL_INVESTIGATORParul Christian, DrPH
Johns Hopkins University
Outcome results
None listed