Assessing Model Parameters for Applying the Retinol Isotope Dilution (RID) Method

Study Overview
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Brief Summary
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For assessing body retinol pools in preschool children, it is recommended that a blood sample is taken 14-21 days after isotope dosing. During this period, dietary intake of vitamin A should be controlled. Shortening of this period as has been validated for adults would reduce the burden for the children as well as improve research efficiency. The aim is to validate a 4-day protocol for assessing body retinol pools in preschool children by modelling data derived by retinol isotope dilution (RID) method. Venous blood samples will be collected of 60 children 4 days after dosing of 0.4 mg 13C-labeled retinyl acetate. A second venous blood sample will be collected at 6, 8, 12 hrs; and 1, 2, 4, 7, 11, 16, 22 and 28 days after dosing in subgroups of 6 children, randomly divided over the 10 additional time points. Body retinol pools will be modelled, and the time point at which a parsimonious model applies (presumably at day 4) will be assessed.

Detailed Description
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For assessing body retinol pools in preschool children, it is recommended that a blood sample is taken 14-21 days after isotope dosing. During this period, dietary intake of vitamin A should be controlled. Shortening of this period as has been validated for adults would reduce the burden for the children as well as improve research efficiency. The aim is to validate a 4-day protocol for assessing body retinol pools in preschool children by modelling data derived by retinol isotope dilution (RID) method. A secondary aim is to compare body retinol pools between children with and without inflammation and to assess the effect of asymptomatic malaria on model parameters. Preschool children (n=60), 36-59 months of age, residing in Telemu, Osun State, Nigeria will be recruited for the study. The study design is an observational pre/post study, for which body retinol pools will be measured using the RID method. Venous blood samples will be collected of all children 4 days after dosing of 0.4 mg 13C-labeled retinyl acetate. A second venous blood sample will be collected at 6, 8, 12 hrs; and 1, 2, 4, 7, 11, 16, 22 and 28 days after dosing in subgroups of 6 children, randomly divided over the 10 additional time points. Children presenting with asymptomatic malaria will be treated, and a convenience subsample (n=10) will undergo a second assessment of body retinol pools determined with a venous blood collection on day 4 post-dosing only. Body retinol pools will be modelled, and the time point at which a parsimonious model applies (presumably at day 4) will be assessed. Presence of asymptomatic malaria and markers of inflammation will be assessed in all children at all time points. Body retinol pools and model parameters between subgroups of children with and without asymptomatic malaria and/or inflammation will be compared. Pre/post comparisons of body retinol pool estimates will be done for the follow up subsample.

Official Title
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Assessing Model Parameters for Applying the Retinol Isotope Dilution (RID) Method in Preschool Nigerian Children Living in an Area With a High Malaria Burden

Conditions
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Vitamin A Deficiency, Malaria, Inflammation

Intervention / Treatment
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* Other: Retinol Isotope Dilution (RID)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Apparently healthy Between 36 and 59 months of age Living in the community of Telemu, Osun State, Nigeria, or its neighbouring communities Exclusion Criteria: Active or recent disease with a potential effect on study outcome Hb concentration <70 g/dL Mental state that is incompatible with participation in the study Recent exposure to 13C-retinol stable isotopes Unwillingness to participate by verbal or physical expression

Ages Eligible for Study
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Minimum Age: 36 Months
Maximum Age: 59 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Retinol Isotope dilution (RID)<br>A once-off dose of 0.4 mg 13C4-retinyl acetate will be administered to subjects as a capsule | Other: Retinol Isotope Dilution (RID)<br>* 13C-retinyl acetate will be administered to subjects in order to assess their body retinol pools<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vitamin A status | Body retinol pool | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of malaria (plasmodium falciparum) | Percentage of children with malaria (Plasmodium falciparum) as determined by a rapid test (CareStart Malaria HRP2) and confirmed by PCR. | 28 days | 
| Prevalence of inflammation | Percentage of children with C-reactive protein (CRP) >5 mg/L and/or alpha-glycoprotein (AGP) >1 g/L | 28 days | 
| Serum retinol | Serum concentration of retinol (HPLC) | 28 days | 
| Blood haemoglobin concentration | Haemoglobin concentration (Quikread) | 28 days | 
| Ferritin concentration | Serum concentration of ferritin (ELISA) | 28 days | 
| Soluble transferrin receptor concentration | Serum concentration of soluble transferrin receptor concentration (ELISA) | 28 days | 
| Retinol binding protein | Serum concentration of retinol binding protein (ELISA) | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin A status, Retinol Isotope Dilution, Nigeria, Preschool children, Malaria, Inflammation