Healthy InfantsNCT03000543
Novel Isotope Dilution Technique to Assess Vitamin A Status
A study testing Vaccine in people with Healthy Infants and Infants With an Inflammatory Condition, run by International Centre for Diarrhoeal Disease Research, Bangladesh at 2 sites in Bangladesh.
Trial summary
Background: There is no reliable method for vitamin A (VA) assessment for infants and young children. Serum VA concentration is not an authenticate indicator of VA status, while existing deuterium- VA isotope dilution methods to determine the whole body VA status require 3 weeks and not applicable for infants and… Read more about this study
- Who is it for?
- Ages 9 to 18 monthsHealthy volunteers can take part
- Conditions the study is for
- Healthy Infants, Infants With an Inflammatory Condition
- What is being tested?
- Vaccine
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 250 participants
- Where
- 2 sitesBangladesh
- Study dates
- 1 Nov 2016to 30 Jun 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 9 to 18 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 9 - 18 months of age
- Infants with normal body temperature and normal CRP (<5 mg/L)
- Infants receive breast milk from the mother at least once per day
- Mothers produce a breast milk containing 30-40 nmol vitamin A /g milk fat
- Infants received a high-dose vitamin A capsules at the time of the most recent national distribution campaign (within the last 2-4 months)
- Mother is 18 - 45 years of age
- Mother and her infant plan to stay in the study area for the duration of the study
Who cannot join
- Mother or infant has chronic disease
- Mother or infant has acute illness on the day of data collection
- Infant is anemic (Hb <90 g/L)
- Infant has weight for length <80% of the reference median
- Infants do not develop inflammation (CRP ≥5 mg/L) after PENTA vaccination
Trial locations and contacts
2 sites in 1 country.
Bangladesh2 sites
Clinical Trail Unit (CTU), icddr,b.
Dhaka, 1212
Shaikh Meshbahuddin Ahmad
Dhaka, 1212
About this study
Official title: Validation of a Novel Isotope Dilution Technique to Assess Vitamin A Status in Infants
Background:
There is no reliable method for vitamin A (VA) assessment for infants and young children. Serum VA concentration is not an authenticate indicator of VA status, while existing deuterium- VA isotope dilution methods to determine the whole body VA status require 3 weeks and not applicable for infants and children. The investigator's research group recently developed a new simplified equation to measure VA pool size in 4-5 days, correlated with compartmental model-predicted value and estimate VA pool size in adults with high precision. In this study, we validate the method in healthy infants and infants with an inflammatory condition.
Read more
Hypothesis:
Whole-body VA status in infant and children can be estimated without accounting for the fractional catabolic rate in the context of an inflammatory condition
Specific Objectives:
In this study, the investigators propose to determine the early time point equation for assessing VA pool size in infants with or without inflammatory condition using model-based compartmental analysis from the fraction of oral dose-derived 13C10-VA and 13C4-VA in plasma over time.
Methods:
A total of 183 infants (9-18 mo of age) will participate in this study in the following two phases of the "Super Kid study" that ensure no more than 2 venous blood samples from each infant, even though multiple time points (at least 4 subjects / time-point) over a 28-day study period will be available for mathematical modeling. In this study, investigators will use two different stable isotopic vitamin A e.g., 13C10-retinyl acetate and 13C4-retinyl acetate. 400 μg of these isotopes, dissolved in 0.5 mL of sunflower oil, will be provided directly into the infant's mouth by using a direct replacement pipette. Mothers will be asked to breastfeed their infant after oral dosing to enhance absorption of the labeled vitamin A. Specific activity of 13C10- and 13C4- retinyl acetate in the blood samples will be measured by liquid chromatography-tandem mass spectrometry (LC/MS/MS). Dietary and morbidity questionnaires will be used. Investigators will also use PENTA vaccines as a means to induce controlled inflammation (closely mimic to natural infection). PENTA is a combination of five different vaccine antigens (Hepatitis B (HBV)/ Haemophilus influenza type b (Hib) / Tetanus-Diphtheria-whole cell Pertussis (TDwP)). This vaccination is beneficial to the infants since the World Health Organization recommends a booster vaccination dose. At the end of the study, PENTA vaccines will also be provided to the study infants in the "no-vaccine" group.
(A) 115 infants will be enrolled randomly into 16 groups of them 40 infants will be in the first group, while other infants will be assigned in the other 15 groups (n=5/group). On day 0 (at 0h), all infants (n=115) will receive an oral dose of 13C10-retinyl acetate. Blood samples (5 mL) will be taken from 6h to 16th day of dosing at 9 different time-points. On day 16 (at 0h), randomly selected 50% infants (n=20) in the first group, as well as 30 infants in the other 6 groups, will receive PENTA vaccines, while the other 50% infants (n=20) in the first Group, as well as 45 infants in the other 9 groups, will receive no vaccines. 24 hours after vaccination (On day 17) a finger-prick blood sample will be obtained from the infants in the vaccinated group to measure CRP (QuikRead go, Orion, Finland). Infants who do not develop inflammation (CRP> 5mg/L) after PENTA vaccination will be excluded from the study. On day 17 (at 0h), all infants (n=115) will receive another oral dose of 13C4-retinyl acetate. Blood samples (5mL) will be collected from day 16 to day 28 at 11 different time-points for each of the vaccinated and non-vaccinated infants. This study will also assess the absorption of isotopic retinol by determining in total excreted stool up to 72 h post isotope dosing in a subsample of infants
(B) 68 infants will be enrolled in this phase. Of them, 28 infants will be assigned randomly into 7 groups (n=4/group). They will receive PENTA vaccines on day -1, and the next day (day 0) they will receive an oral dose of 13C4-retinyl acetate. Blood samples (5mL) will be collected from day 1 to day 28 at 8 different time points. In a separate design, 40 infants will receive an oral dose of 13C10-retinyl acetate on day 0 and blood samples (5mL) will be collected on day 4. On day 7 they all will receive another oral dose of 13C4-retinyl acetate (400 μg, dissolved in 0.5 mL of sunflower oil). On day 10, infants will receive PENTA vaccines (n=30) or no vaccine (n=10) and 1-day after vaccination, blood samples (5 mL) will be obtained from infants who develop inflammation (CRP> 5mg/L) in the vaccine group and also from infants in the control group (day 11).
Outcome measures:
The early time point equation for assessing VA pool size in a group of infants with or without inflammation
- Being tested
- Vaccine
- Keywords
- vitamin A, vitamin A isotope, Inflammation
- Medical subject headings
- Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VaccineBiological
Also called PENTA
Pentavalent vaccine. It is a combination of five different antigens (Hepatitis B (HBV)/ Haemophilus influenzae type b (HiB) / Tetanus-Diphtheria-whole cell Pertussis (TDwP)).
| Study group | Role | What they receive |
|---|---|---|
| Vitamin A pool size in infants without inflammatory condition | No intervention | Assessing vitamin A (VA) pool size in infants without inflammatory condition using model based compartmental analysis from the fraction of oral dose-derived 13C10-VA and 13C4-VA in plasma over time. |
| Vitamin A pool size in infants with inflammatory condition | Experimental | Assessing vitamin A (VA) pool size in infants without inflammatory condition using model based compartmental analysis from the fraction of oral dose-derived 13C10-VA and 13C4-VA in plasma over time. Receives: Biological: Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Vitamin A pool size in infants with or without inflammation
Measured: Kinetic study for 28 days for each of the 2 groups of infants
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2016 (estimated)
- Study start1 Nov 2016
- Primary completion30 Jun 2019
- Study completion30 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Healthy InfantsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 250 participants (actual)
Sponsor and investigators
- Lead sponsor
- International Centre for Diarrhoeal Disease Research, Bangladesh
- Sponsor type
- University, hospital or other
- Collaborators
- Newcastle University
- Responsible party
- Sponsor
- Investigators
- Shaikh M Ahmad, Ph.D., Principal investigator, International Centre for Diarrhoeal Disease Research, Bangladesh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03000543
- Sponsor's protocol ID
- PR-14126
- Status last verified
- Mar 2018
- First submitted
- 14 Dec 2016
- Last updated
- 20 Aug 2019
- Results posted
- No
Publications
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.
PubMed 31535129
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Validation of a Novel Isotope Dilution Technique to Assess Vitamin A Status in Infants
- ClinicalTrials.gov ID
- NCT03000543
- Acronym / sponsor ID
- PR-14126
- Keywords
- vitamin A, vitamin A isotope, Inflammation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 250 participants (actual)
- Lead sponsor
- International Centre for Diarrhoeal Disease Research, BangladeshUniversity, hospital or other
- Collaborators
- Newcastle University
- Study start
- 1 Nov 2016 (actual)
- Primary completion
- 30 Jun 2019 (actual)
- Study completion
- 30 Jun 2019 (actual)
- First posted
- 22 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
There is no reliable method for vitamin A (VA) assessment for infants and young children. Serum VA concentration is not an authenticate indicator of VA status, while existing deuterium- VA isotope dilution methods to determine the whole body VA status require 3 weeks and not applicable for infants and children. The investigator's research group recently developed a new simplified equation to measure VA pool size in 4-5 days, correlated with compartmental model-predicted value and estimate VA pool size in adults with high precision. In this study, we validate the method in healthy infants and infants with an inflammatory condition.
Hypothesis:
Whole-body VA status in infant and children can be estimated without accounting for the fractional catabolic rate in the context of an inflammatory condition
Specific Objectives:
In this study, the investigators propose to determine the early time point equation for assessing VA pool size in infants with or without inflammatory condition using model-based compartmental analysis from the fraction of oral dose-derived 13C10-VA and 13C4-VA in plasma over time.
Methods:
A total of 183 infants (9-18 mo of age) will participate in this study in the following two phases of the "Super Kid study" that ensure no more than 2 venous blood samples from each infant, even though multiple time points (at least 4 subjects / time-point) over a 28-day study period will be available for mathematical modeling. In this study, investigators will use two different stable isotopic vitamin A e.g., 13C10-retinyl acetate and 13C4-retinyl acetate. 400 μg of these isotopes, dissolved in 0.5 mL of sunflower oil, will be provided directly into the infant's mouth by using a direct replacement pipette. Mothers will be asked to breastfeed their infant after oral dosing to enhance absorption of the labeled vitamin A. Specific activity of 13C10- and 13C4- retinyl acetate in the blood samples will be measured by liquid chromatography-tandem mass spectrometry (LC/MS/MS). Dietary and morbidity questionnaires will be used. Investigators will also use PENTA vaccines as a means to induce controlled inflammation (closely mimic to natural infection). PENTA is a combination of five different vaccine antigens (Hepatitis B (HBV)/ Haemophilus influenza type b (Hib) / Tetanus-Diphtheria-whole cell Pertussis (TDwP)). This vaccination is beneficial to the infants since the World Health Organization recommends a booster vaccination dose. At the end of the study, PENTA vaccines will also be provided to the study infants in the "no-vaccine" group.
(A) 115 infants will be enrolled randomly into 16 groups of them 40 infants will be in the first group, while other infants will be assigned in the other 15 groups (n=5/group). On day 0 (at 0h), all infants (n=115) will receive an oral dose of 13C10-retinyl acetate. Blood samples (5 mL) will be taken from 6h to 16th day of dosing at 9 different time-points. On day 16 (at 0h), randomly selected 50% infants (n=20) in the first group, as well as 30 infants in the other 6 groups, will receive PENTA vaccines, while the other 50% infants (n=20) in the first Group, as well as 45 infants in the other 9 groups, will receive no vaccines. 24 hours after vaccination (On day 17) a finger-prick blood sample will be obtained from the infants in the vaccinated group to measure CRP (QuikRead go, Orion, Finland). Infants who do not develop inflammation (CRP> 5mg/L) after PENTA vaccination will be excluded from the study. On day 17 (at 0h), all infants (n=115) will receive another oral dose of 13C4-retinyl acetate. Blood samples (5mL) will be collected from day 16 to day 28 at 11 different time-points for each of the vaccinated and non-vaccinated infants. This study will also assess the absorption of isotopic retinol by determining in total excreted stool up to 72 h post isotope dosing in a subsample of infants
(B) 68 infants will be enrolled in this phase. Of them, 28 infants will be assigned randomly into 7 groups (n=4/group). They will receive PENTA vaccines on day -1, and the next day (day 0) they will receive an oral dose of 13C4-retinyl acetate. Blood samples (5mL) will be collected from day 1 to day 28 at 8 different time points. In a separate design, 40 infants will receive an oral dose of 13C10-retinyl acetate on day 0 and blood samples (5mL) will be collected on day 4. On day 7 they all will receive another oral dose of 13C4-retinyl acetate (400 μg, dissolved in 0.5 mL of sunflower oil). On day 10, infants will receive PENTA vaccines (n=30) or no vaccine (n=10) and 1-day after vaccination, blood samples (5 mL) will be obtained from infants who develop inflammation (CRP> 5mg/L) in the vaccine group and also from infants in the control group (day 11).
Outcome measures:
The early time point equation for assessing VA pool size in a group of infants with or without inflammation
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vitamin A pool size in infants without inflammatory condition | No intervention | –Assessing vitamin A (VA) pool size in infants without inflammatory condition using model based compartmental analysis from the fraction of oral dose-derived 13C10-VA and 13C4-VA in plasma over time. |
| Vitamin A pool size in infants with inflammatory condition | Experimental | Biological: VaccineAssessing vitamin A (VA) pool size in infants without inflammatory condition using model based compartmental analysis from the fraction of oral dose-derived 13C10-VA and 13C4-VA in plasma over time. |
Who may qualify
- Ages
- 9 to 18 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 9 - 18 months of age
- Infants with normal body temperature and normal CRP (<5 mg/L)
- Infants receive breast milk from the mother at least once per day
- Mothers produce a breast milk containing 30-40 nmol vitamin A /g milk fat
- Infants received a high-dose vitamin A capsules at the time of the most recent national distribution campaign (within the last 2-4 months)
Key exclusion criteria (5 listed)
- Mother or infant has chronic disease
- Mother or infant has acute illness on the day of data collection
- Infant is anemic (Hb <90 g/L)
- Infant has weight for length <80% of the reference median
- Infants do not develop inflammation (CRP ≥5 mg/L) after PENTA vaccination
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VaccineAlso: PENTAPentavalent vaccine. It is a combination of five different antigens (Hepatitis B (HBV)/ Haemophilus influenzae type b (HiB) / Tetanus-Diphtheria-whole cell Pertussis (TDwP)). | Biological | Vitamin A pool size in infants with inflammatory condition |
Primary outcome
Vitamin A pool size in infants with or without inflammation
Time frame: Kinetic study for 28 days for each of the 2 groups of infants
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2019.
- Derived from this study: PubMed 31535129Ford 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shaikh M Ahmad, Ph.D. principal investigator
International Centre for Diarrhoeal Disease Research, Bangladesh
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vaccine in people with Healthy Infants and Infants With an Inflammatory Condition, run by International Centre for Diarrhoeal Disease Research, Bangladesh at 2 sites in Bangladesh.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Bangladesh. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Vitamin A pool size in infants with or without inflammation (time frame: Kinetic study for 28 days for each of the 2 groups of infants). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03000543, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2019.