Clinical trial NCT03345147: Estimation of Vitamin A Stores in Children and Women in Guatemala and Relation With Potential Toxicity Markers
Official title: LOAEL/NOAEL and UL Determination in Guatemala - Estimation of Vitamin A Stores in Children and Women and Correlation With Potential Toxicity Markers
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Vitamin A Status
Keywords: Vitamin A
Isotopic dilution
dietary assessment
Lead sponsor: Institute of Nutrition of Central America and Panama
Sponsor class: OTHER
Collaborators: name: Newcastle University
name: Bill and Melinda Gates Foundation
name: International Atomic Energy Agency
First posted: 2017-11-17
Enrollment: 178
Sex: ALL
Minimum age (years): 3
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children and Women from Guatemala peri-urban areas or areas where High Vitamin A foods intake is reported. Convenience sampling according to the availability (time to participate in the study) of the participant, and acceptance of Blood sampling and Dietary assessments

Brief summary: The goal of this study is to assess whether 3-5 years-old children who have Vitamin A intakes above the tolerable upper intake level (UL=900 ug per day) have higher total body Vitamin A stores and biomarkers of excessive vitamin A status, compared to children with Normal Vitamin A intakes (250-600 ug per day).

Detailed description: The goal of this study is to assess whether VA intakes above the tolerable upper intake level (UL) and exposure to multiple programs are associated with are associated with 1) exposure to multiple VA intervention programs, and 2) elevated liver vitamin A concentration and biomarkers of excess vitamin A. Guatemala was selected as a study site because the country has a long standing national fortification program for vitamin A in sugar (law since 1975, re-launched and maintained since the 90´s). Typically, fortified sugar is used in more than 90% of households at average concentrations of 9 to 10 µg/g of sugar. VA fortified foods, in the form of fortified sugar, foods prepared with fortified sugar and other fortified foods, reach children from 2 years old to adulthood. On the other hand, high dose VA supplements, provided by local health services, only reached 10.5% of children ages 6-59 month in 2013. Children ages 2-3 and 4-5 years old with VA intakes above and below the UL will be recruited together with their mothers to assess the cumulative effect of fortification on young children and their mothers. Data from Program of Food and Nutrition Security (PROSAN), of the Ministry of Health, Guatemala in 2013, shows that coverage in the 30 Health Areas of the country is 17.9%, the lowest is 4.4% (San Marcos) and the largest 33% (Petén). Four of the 30 Region Areas correspond to the Department of Guatemala, in which urban and peri-urban areas of Guatemala City are included. In Central and North-West Guatemala Areas, coverage is 23 and 22% respectively, both above national average coverage and within the 10 out of 30 top coverages. According to PROSAN data for Micronutrient Powders in 2013, all four regions North-East, North-West, South, and Central Guatemala areas are also around or above the national coverage (14%) with 21.8, 11.2, 17.3 and 13.8% coverage. Another advantage of remaining in the 4 areas of Health around Guatemala city is that the four combined amount for 300,000 children of 0-59 month-old, that is more than 15% of the national children population reported. Even if coverages are low, population density will easier children recruitment.

Eligibility criteria: Inclusion Criteria:

* Children 3-5 years old and their mothers
* Child VA intake must be above 250 micrograms/day
* Children must be apparently healthy, Hemoglobin\>9 g/dL at recruitment point, C-reactive protein\<5 mg/L. For Women, Hemoglobin\>10 g/dL, C-reactive protein\<5 mg/L

Exclusion Criteria:

°Children with Congenital or chronical diseases, reported illnesses 1 week before the test. For Women: Pregnancy or lactation, Previously known Chronic Diseases

Primary outcomes:
measure: Total Vitamin A stores among 3-5 years-old children, in micromoles
timeFrame: 28-day study period
measure: Total dietary vitamin A intake among 3-5 years-old children, in micrograms (ug)
timeFrame: 28-day study period
Secondary outcomes:
measure: Plasma retinol among 3-5 years-old children
timeFrame: 28-day study period
measure: Plasma retinol binding protein among 3-5 years-old children
timeFrame: 28-day study period
measure: Plasma Transthyretin among 3-5 years-old children
timeFrame: 28-day study period
measure: Bone Health markers among 3-5 years-old children
timeFrame: 28-day study period
measure: Liver function markers among 3-5 years-old children
timeFrame: 28-day study period
measure: Plasma retinol among women
timeFrame: 28-day study period
measure: Plasma retinol binding protein among women
timeFrame: 28-day study period
measure: Plasma Transthyretin among women
timeFrame: 28-day study period
measure: Total dietary vitamin A intake among women, in micrograms (ug)
timeFrame: 28-day study period
Other outcomes:
measure: Hemoglobin concentration in children
timeFrame: At recruitment
measure: Children weight and length
timeFrame: At recruitment
measure: Systemic inflammation in children
timeFrame: At recruitment
measure: Iron status in children
timeFrame: 28-day study period
measure: Zinc status in children
timeFrame: 28-day study period
Locations:
city: Guatemala City
country: Guatemala
facility: Mixco, La Comunidad City Hall
city: Guatemala City
country: Guatemala
facility: Santa Catarina Pinula City Hall
city: Guatemala
country: Guatemala
facility: Sacatepequez City Hall
Study officials:
affiliation: Institute of Nutrition of Central America and Panama
name: Dora I Mazariegos, MsSc
role: PRINCIPAL_INVESTIGATOR
References:
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.