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Trial record 1 of 19 for:    vitamin A | Interventional Studies | Bangladesh | Child
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Novel Isotope Dilution Technique to Assess Vitamin A Status and Hypervitaminosis A

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ClinicalTrials.gov Identifier: NCT03000543
Recruitment Status : Recruiting
First Posted : December 22, 2016
Last Update Posted : December 22, 2016
Sponsor:
Collaborator:
Newcastle University
Information provided by (Responsible Party):
International Centre for Diarrhoeal Disease Research, Bangladesh

Brief Summary:

Background:

  1. Burden: Recently Bangladesh has introduced mandatory vitamin A (VA) fortification of refined edible oil while high dose VA supplementations for infants and children are still in place as part of national program. Thus preschool children are plausible at risk of hypervitaminosis A.
  2. Knowledge gap: Serum VA concentration is not an authenticate indicator of VA status, while existing deuterium- VA isotope dilution methods to determine whole body VA status require 3 weeks and not applicable for infants and children.
  3. Relevance: Our research group has recently developed a new simplified equation to measure VA pool size in 4-5 days, highly correlated with compartmental model-predicted value and estimate VA pool size in adults with high precision. However, it is not clear whether this new simplified equation also works in infants and children. In this proposed study, we validate the method in healthy infants and infants with inflammatory condition as well as in children with adequate and high dietary VA intake.

Hypothesis: (1) Whole-body VA status in infant and children can be estimated without accounting for fractional catabolic rate in the context of inflammatory condition or higher dietary VA intake (2) Fortification of commonly consumed food item with VA along with periodic high dose VA supplementation would increase the risk of hypervitaminosis A among preschool children in Bangladesh

Methods: Our study comprises two studies. "Study 01" will be undertaken in infants while "Study 02" for preschool children. At first we need to undertake one feasibility study to verify whether the oral dose of 400 μg 13C10 or 13C3- retinyl acetate (isotopic VA) that we propose to use in this study would work in infants as we observed in adults, secondly, whether PENTA valent vaccines induce inflammation in infants (plasma CRP as maker) that closely mimics natural infection. We need such infants with inflammatory condition in "Study 01" to answer the question of whether the isotope dilution technique will still work in children who undergo inflammation. Information of the reliability of the retinol isotope dilution technique in infectious conditions is important as national dietary assessment surveys often observe children with chronic or latent infection. To minimize the taking of multiple blood samples from each infant/child in both studies, a "super kid study" design will be adopted that ensure no more than 2 venous blood samples from each infant/child, even though multiple time points (at least 5 subjects / time-point) over a 28-day study period will be available for mathematical modelling. In "Study 01" a total of 115 infants (9-11 mo) will receive an oral dose of 13C10- retinyl acetate (400 μg) dissolved in 0.5 mL of sunflower oil and then blood samples will be taken from 6h to 16th day at 9 different time-points. On day 16, a single dose PENTA vaccine will be provided to the randomly selected 50% of infants. On day 17, another type of stable isotopic VA e.g. 13C3- retinyl acetate (400 μg) will be orally supplemented to all infants. Blood sample will be collected from day 16 to day 28 at 11 different time-points for each of the vaccine and non-vaccine groups. In "Study 02" 50 children (3-5y) in each of the "adequate dietary VA" intake group and "higher dietary VA" intake group will be enrolled to receive an oral dose of 13C10- retinyl acetate (400 μg). Blood sample will be collected from 6h to day 28 at 11 time-points for each of the two groups. Specific activity of 13C10-VA and 13C3-VA from the blood samples will be measured by liquid chromatography-tandem mass spectrometry (LC/MS/MS). Plasma biomarkers of VA toxicity e.g. bone metabolism, liver fibrogenesis and VA metabolites will be measured in the children of "Study 02".

Outcome measures/variables: (1) The early time point equation for assessing VA pool size in a group of infants with or without inflammation and in a group of children with adequate or with high dietary VA intake. (2) The association between biomarkers of VA toxicity and estimated liver vitamin A concentration in preschool children at risk of hypervitaminosis A.


Condition or disease Intervention/treatment Phase
Inflammation High Vitamin A Store Adequate Vitamin A Store Device: Stable isotope labelled vitamin A Phase 1 Phase 2

Study Type : Interventional
Estimated Enrollment : 245 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Validation of a Novel Isotope Dilution Technique to Assess Vitamin A Status in Infants and Children in Bangladesh and Assessment of Plausible Risk of Hypervitaminosis A Among Preschoolers in Bangladesh
Study Start Date : November 2016
Estimated Primary Completion Date : December 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vitamin A
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Vitamin A pool size in infants without inflammatory condition
Assessing vitamin A pool size in infants without inflammatory condition using model based compartmental analysis from the fraction of oral dose-derived 13C10-VA and 13C3-vitamin A in plasma over time.
Device: Stable isotope labelled vitamin A
Oral dose of 400 μg 13C10 or 13C3- retinyl acetate (stable isotope labelled vitamin A) dissolved in 0.5 mL of sunflower oil
Other Name: 13C10 or 13C3- retinyl acetate
Experimental: Vitamin A pool size in infants with inflammatory condition
Assessing vitamin A pool size in infants with inflammatory condition using model based compartmental analysis from the fraction of oral dose-derived 13C10-VA and 13C3-vitamin A in plasma over time.
Device: Stable isotope labelled vitamin A
Oral dose of 400 μg 13C10 or 13C3- retinyl acetate (stable isotope labelled vitamin A) dissolved in 0.5 mL of sunflower oil
Other Name: 13C10 or 13C3- retinyl acetate
Experimental: Vitamin A pool size in children with adequate store
Assessing vitamin A pool size in children with adequate vitamin A store using model based compartmental analysis from the fraction of oral dose-derived 13C10-VA in plasma over time.
Device: Stable isotope labelled vitamin A
Oral dose of 400 μg 13C10 or 13C3- retinyl acetate (stable isotope labelled vitamin A) dissolved in 0.5 mL of sunflower oil
Other Name: 13C10 or 13C3- retinyl acetate
Experimental: Vitamin A pool size in children with high store
Assessing vitamin A pool size in children with high vitamin A store using model based compartmental analysis from the fraction of oral dose-derived 13C10-VA in plasma over time.
Device: Stable isotope labelled vitamin A
Oral dose of 400 μg 13C10 or 13C3- retinyl acetate (stable isotope labelled vitamin A) dissolved in 0.5 mL of sunflower oil
Other Name: 13C10 or 13C3- retinyl acetate



Primary Outcome Measures :
  1. Vitamin A pool size in infants with or without inflammation [ Time Frame: 28 days ]
  2. Vitamin A pool size in children with adequate or high dietary vitamin A intake [ Time Frame: 28 days ]

Secondary Outcome Measures :
  1. Bio-markers of vitamin A toxicity in children with high vitamin A store [ Time Frame: 28 days ]


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Ages Eligible for Study:   9 Months to 5 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Inclusion criteria for study 01:

    1. 9 - 11 months of age
    2. Infants with normal body temperature and normal CRP (<5 mg/L)
    3. Infants receive breast milk from the mother at least once per day
    4. Mothers produce a breast milk containing 30-40 nmol vitamin A /g milk fat (~1.5-2.0 µmol/L)
    5. Infants received a high-dose vitamin A capsules at the time of the most recent national distribution campaign (within the last 2-4 months)
    6. Mother is 18 - 45 years of age
    7. Mother and her infant plan to stay in the study area for the duration of the study
  • Inclusion criteria for study 02:

    1. 3-5 years of age
    2. Children with normal body temperature and normal CRP (<5 mg/L)
    3. Received a high-dose vitamin A capsules at the time of the most recent national distribution campaign (within the last 2-4 months)
    4. Mother is 18 - 45 years of age
    5. Mother and her child plan to stay in the study area for the duration of the study

Exclusion Criteria:

  • Exclusion criteria for study 01:

    1. Mother or infant has chronic disease
    2. Mother or infant has acute illness on the day of data collection
    3. Infant is anemic (Hb <100 g/L)
    4. Infant has weight for length <80% of the reference median
    5. Infants do not develop inflammation (CRP >5 mg/L) after PENTA vaccination.
  • Exclusion criteria for study 02:

    1. Mother or child has chronic disease
    2. Mother or child has acute illness on the day of data collection
    3. Child is anemic (Hb <110 g/L)
    4. Child has weight for length <80% of the reference median

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03000543


Contacts
Contact: Shaikh M Ahmad, Ph.D. 8860523-32 ext 3469 smeahmad@icddrb.org
Contact: Munirul Islam, Ph.D. 8860523-32 ext 2352 mislam@icddrb.org

Locations
Bangladesh
Clinical Trail Unit (CTU), icddr,b. Recruiting
Dhaka, Bangladesh, 1212
Contact: Rubhana Raqib, Ph.D.    8860523-32 ext 2415    rubhana@icddrb.org   
Sponsors and Collaborators
International Centre for Diarrhoeal Disease Research, Bangladesh
Newcastle University
Investigators
Principal Investigator: Shaikh M Ahmad, Ph.D. International Centre for Diarrhoeal Disease Research, Bangladesh

Responsible Party: International Centre for Diarrhoeal Disease Research, Bangladesh
ClinicalTrials.gov Identifier: NCT03000543     History of Changes
Other Study ID Numbers: PR-14126
First Posted: December 22, 2016    Key Record Dates
Last Update Posted: December 22, 2016
Last Verified: December 2016

Keywords provided by International Centre for Diarrhoeal Disease Research, Bangladesh:
Infants
Children
Adequate or high vitamin A store

Additional relevant MeSH terms:
Vitamin A
Retinol palmitate
Retinol acetate
Inflammation
Hypervitaminosis A
Pathologic Processes
Nutrition Disorders
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Anticarcinogenic Agents
Antineoplastic Agents
Adjuvants, Immunologic
Immunologic Factors