Clinical trial NCT03030339: Vitamin A Status and Risk of Excessive Vitamin A Intake Among Urban Filipino Children
Official title: Vitamin A Status and Risk of Excessive Vitamin A Intake Among Urban Filipino Children Exposed to Multiple Vitamin A Intervention Programs
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Vitamin A Status
Keywords: Vitamin A status
infant
dietary assessment
retinol isotope dilution
breast milk intake
Lead sponsor: University of California, Davis
Sponsor class: OTHER
Collaborators: name: Newcastle University
name: Penn State University
name: Helen Keller International
name: Food and Nutrition Research Institute, Philippines
name: Global Alliance for Improved Nutrition
name: Bill and Melinda Gates Foundation
name: International Atomic Energy Agency
First posted: 2017-01-25
Enrollment: 123
Sex: ALL
Minimum age (years): 12
Maximum age (years): 18
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children 12-18 months of age and their mothers in selected neighborhoods in the National Capital Region of the Philippines

Brief summary: The goal of this study is to assess whether children 12-18 months of age who are exposed to multiple large-scale vitamin A programs, and who are likely to have vitamin A intakes above the tolerable upper intake level (UL), have higher total body vitamin A stores and biomarkers of excessive vitamin A status, compared to children 12-18 months of age who have adequate vitamin A intake.

Detailed description: This is an observational study with 3 groups, which are identified using a screening tool to obtain information on exposure to vitamin A programs and consumption of vitamin A-rich foods and supplements. Children and their mothers are studied over the course of one month to determine 1) child total body vitamin A stores, using the 13C retinol isotope dilution method, 2) the child's vitamin A intake, using multiple dietary assessment methods, 3) total breast milk intake (among breastfeeding children), using the dose-to-mother deuterium dilution method, and 4) potential biomarkers of excessive vitamin A status, including markers of bone and liver health. Blood collection is structured in a "Super-Child" design, to construct plasma retinol kinetic curves. Other indicators related to vitamin A nutrition among children will be measured, in addition to the vitamin A intake and breast milk vitamin A concentration (for breastfeeding mothers) of the mother.

Eligibility criteria: Inclusion Criteria:

* Children 12-18 months of age, and their mothers (18-49 years of age)
* Living in selected communities in the National Capital Region of the Philippines
* The mother and child must plan to stay in the study area for the duration of the study.
* Child's estimated vitamin A intake and exposure to vitamin A programs must meet eligibility criteria for one of three groups, based on a screening questionnaire administered by an interviewer to the child's mother.

Eligibility criteria for children in Group 1: 1) consumed MNP or a multi-vitamin preparation that contains vitamin A in the previous 7 days, 2) consumed at least one fortified staple food (oil or wheat flour) in the previous 7 days, 3) consumed breast milk or fortified milk in the past 24 hours, 4) received a high-dose VA capsule during the previous month, and 5) received a screening tool 'score' suggesting VA intake above 600 µg retinol/d.

Eligibility criteria for children in Group 2: will include children who: 1) consumed MNP or a multi-vitamin A preparation that contains vitamin A in the previous 7 days, 2) consumed at least one fortified staple food (oil or wheat flour) in the previous 7 days, 3) consumed breast milk or fortified milk in the past 24 hours, 4) received a high-dose VA capsule in the previous 3-6 months, and 5) received a screening tool 'score' suggesting VA intake above 600 µg retinol/d.

Eligibility criteria for children in Group 3: will include children who: 1) received a high dose VA capsule during the previous 3-6 months, and 2) received a screening tool 'score' suggesting VA intake 200-500 µg/d.

Exclusion Criteria:

* The child did not receive a high-dose VA capsule during the most recent national campaign
* The mother or child has chronic disease
* The child has moderate or severe anemia (Hb \<10 g/dL)
* The mother or child has signs or symptoms of vitamin A deficiency (Bitot's spots, conjunctival xerosis, nightblindness)
* The child has weight for length \< -2 z-scores of the median of the WHO growth standards
* The mother is breastfeeding more than one child

Primary outcomes:
measure: Total body vitamin A stores among children 12-18 mo of age
timeFrame: 28-day study period
measure: Total dietary vitamin A intake among children 12-18 mo of age
timeFrame: 28-day study period
measure: Total breast milk intake (among breastfeeding children 12-18 mo of age)
timeFrame: 15-day study period
Secondary outcomes:
measure: Plasma or serum retinol among children 12-18 mo of age
timeFrame: 28-day study period
measure: Plasma or serum retinol-binding protein among children 12-18 mo of age
timeFrame: 28-day study period
measure: Ratio of retinol to retinol-binding protein among children 12-18 mo of age
timeFrame: 28-day study period
measure: Retinol metabolites among children 12-18 mo of age
timeFrame: 28-day study period
measure: Transthyretin among children 12-18 mo of age
timeFrame: 28-day study period
measure: Bone health markers among children 12-18 mo of age
timeFrame: 28-day study period
measure: Liver function markers among children 12-18 mo of age
timeFrame: 28-day study period
measure: Consumption of fortifiable foods among women
timeFrame: 28 day study period
measure: Consumption of fortifiable foods among children
timeFrame: 28 day study period
measure: Total vitamin A intake among women
timeFrame: 28-day study period
measure: Breast milk vitamin A concentration among lactating women
timeFrame: 28-day study period
Other outcomes:
measure: Total food and nutrient intakes among women
timeFrame: 28-day study period and 30 days prior to study period
measure: Total food and nutrient intakes among children
timeFrame: 28-day study period and 30 days prior to study period
measure: Infant weight-for-length z score
timeFrame: At recruitment
measure: Infant length-for-age z score
timeFrame: At recruitment
measure: Systemic inflammation among children
timeFrame: 28-day study period
measure: Iron status among children
timeFrame: 28-day study period
measure: Zinc status among children
timeFrame: 28-day study period
measure: Hepatitis infection among children
timeFrame: 28-day study period
measure: Genetic markers related to vitamin A metabolism among children
timeFrame: 28-day study period
measure: Infant hemoglobin concentration
timeFrame: At enrollment
measure: Infant morbidity symptoms
timeFrame: 28-day study period and previous 7 days
Locations:
city: Mandaluyong
country: Philippines
facility: Block 37 Health Center
state: National Capital Region
Study officials:
affiliation: Newcastle University
name: Georg Lietz
role: STUDY_DIRECTOR
References:
citation: Engle-Stone R, Miller JC, Reario MFD, Arnold CD, Stormer A, Lafuente E, Oxley A, Capanzana MV, Cabanilla CVD, Ford JL, Clark A, Velavan TP, Brown KH, Lietz G, Haskell MJ. Filipino Children with High Usual Vitamin A Intakes and Exposure to Multiple Sources of Vitamin A Have Elevated Total Body Stores of Vitamin A But Do Not Show Clear Evidence of Vitamin A Toxicity. Curr Dev Nutr. 2022 Jul 25;6(8):nzac115. doi: 10.1093/cdn/nzac115. eCollection 2022 Aug.
citation: Oxley A, Engle-Stone R, Miller JC, Reario MFD, Stormer A, Capanzana MV, Cabanilla CVD, Haskell MJ, Lietz G. Determination of Vitamin A Total Body Stores in Children from Dried Serum Spots: Application in a Low- and Middle-Income Country Community Setting. J Nutr. 2021 May 11;151(5):1341-1346. doi: 10.1093/jn/nxaa446.
citation: Ford JL, Green JB, Haskell MJ, Ahmad SM, Mazariegos Cordero DI, Oxley A, Engle-Stone R, Lietz G, Green MH. Use of Model-Based Compartmental Analysis and a Super-Child Design to Study Whole-Body Retinol Kinetics and Vitamin A Total Body Stores in Children from 3 Lower-Income Countries. J Nutr. 2020 Feb 1;150(2):411-418. doi: 10.1093/jn/nxz225.