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

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

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.

Study Overview

• Status: Completed
• Conditions: Inflammation; Malaria; Vitamin A Deficiency
• Intervention / Treatment: Other: Retinol Isotope Dilution (RID)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Nigeria
  • Oyo State
    • Ibadan, Oyo State, Nigeria
      • University of Ibadan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 4 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body weight	Body weight will be measured to the nearest 0.1 kg with a weighing scale	Baseline
Dietary intake of energy, protein, fat, carbohydrates, vitamins and minerals	Group mean intake of macronutrients and micronutrients, assessed by 24h recall	Baseline
Body length	Body length will be measured to the nearest 1 cm with a stadiometer	Baseline

Collaborators and Investigators

• Sponsor: Wageningen University
• Collaborators: University of California, Davis; Penn State University; University of Ibadan; Newcastle University; HarvestPlus

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: November 11, 2016
• First Submitted That Met QC Criteria: December 14, 2016
• First Posted (Estimate): December 19, 2016

Study Record Updates

• Last Update Posted (Actual): August 25, 2017
• Last Update Submitted That Met QC Criteria: August 24, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Inflammation; Malaria; Preschool children; Vitamin A status; Nigeria; Retinol Isotope Dilution
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Eye Diseases; Nutrition Disorders; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Avitaminosis; Deficiency Diseases; Malnutrition; Vision Disorders; Inflammation; Malaria; Night Blindness; Vitamin A Deficiency; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin A
• Other Study ID Numbers: WageningenU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No