Vitamin A DeficiencyNCT02027610
Vitamin A, Stool Microbiota and Vaccine Response in Bangladeshi Infants
An observational study of Vitamin A Deficiency, run by USDA, Western Human Nutrition Research Center at 3 sites in 2 countries.
Trial summary
Vitamin A deficiency (VAD) increases the risk of death from infections in infants and young children. The World Health Organization (WHO) recommends high-dose vitamin A supplementation (VAS) from 6-59 months of age to reduce the risk of death in countries where VAD is common. Read more about this study
- Who is it for?
- Ages 12 to 24 months
- Conditions the study is for
- Vitamin A Deficiency
- How many people
- 258 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Oct 2014to Sep 2015
- Phase
- Observational
- 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 12 to 24 months
- All sexes
- No healthy volunteers
- Child
Study population: The present study will recruit infants who completed NCT01583972 when they are from 12 to 24 months of age. Mothers of these infants will also be recruited for collection of DNA from a cheek swab.
Who may be able to join
- for infant: completion of NCT01583972
- for mother: mother of study infant
Who cannot join
- none
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
United States2 sites
University of California, Davis
Davis, California, 95616
USDA Western Human Nutrition Research Center
Davis, California, 95616
Bangladesh1 site
International Centre for Diarrhoeal Disease Research, Bangladesh
Dhaka, 1212
About this study
Official title: Newborn Vitamin A Supplementation, Gut Microbiota and Vaccine Response During the Second Year of Life in Bangladeshi Infants
Vitamin A deficiency (VAD) increases the risk of death from infections in infants and young children. The World Health Organization (WHO) recommends high-dose vitamin A supplementation (VAS) from 6-59 months of age to reduce the risk of death in countries where VAD is common. Such countries include Bangladesh, where this study is being conducted. While providing VAS at 6 months is recommended, providing VAS at birth may also decrease the risk of death since newborn infants are also at risk of VAD. VAS presumably reduces infant mortality by improving the immune response to infection and immunization. Vitamin A particularly affects the development and function of T cells, which develop in the thymus and are a key component of the memory response to infection and immunization. Vitamin A is important for development of an important class of T cells, regulatory T-cells, in the intestine. Regulatory T-cells prevent over-reaction of the immune system to substances the immune system might otherwise treat as harmful such as food or the healthy bacteria in the intestine. VAD could disrupt the normal colonization of the infant's intestinal tract and cause a condition called "dysbiosis" where abnormal bacteria flourish and adversely affect the infant's immune system. Dysbiosis may disrupt the immune response to injectable and oral vaccines. VAS at birth may prevent dysbiosis and thus improve immune function, response to vaccines, and child survival. The investigators recently completed an intervention trial in Bangladeshi infants (NCT01583972) examining the effect of VAS at birth on immune function and response to vaccines administered from birth to 14 wk of age. The present study will recruit infants who completed NCT01583972 when they are from 12 to 24 m of age to determine if VAS at birth affects the responses to these same vaccines when they are measured during the second year of life. The investigators will examine the effect of VAS at birth on gut microbiota measured early in infancy and during the second year of life, and explore the association of the gut microbiota with vaccine response. Mothers of study infants will participate in the study because the breast milk oligosaccharide content strongly affects gut microbiota composition and the "secretor status" of the mother, which can be determined from maternal FUT2 genotype, strongly affects breast milk oligosaccharide content.
Read the detailed description
Hypotheses and Specific Aims The investigators will test the hypotheses that VAS at birth will (1) improve production of new T cells at 1-2 yr of age; (2) improve T-cell memory responses at 1-2 yr of age to vaccines given early in infancy (birth - 14 wk); and (3) alter intestinal colonization early in infancy (6, 11 and 15 wk) and at 1-2 yr of age to increase Bifidobacterium and other healthy bacteria and decrease Proteobacteria and other harmful bacteria. Because the "secretor status" of the mother affects the carbohydrate content of the breastmilk, which can in turn affect Bifidobacterium growth in the infant gut, the "secretor status" of the mother will be determined. Furthermore these differences in composition of the intestinal bacteria will be associated with greater immunologic responses to oral and systemic vaccines.
Specific Aim 1: Determine if VAS or placebo at birth affect the blood concentration and thymic output of naïve T-cells at 1-2 yr of age. Specific Aim 2: Determine if VAS or placebo at birth affect T-cell mediated responses at 1-2 yr of age to vaccines given early in infancy, including serum and intestinal antibody levels, vaccine-specific proliferative responses by T cells and cytokine production by T cells. Specific Aim 3: Determine if VAS or placebo at birth affect the relative abundance of healthy intestinal bacteria and common harmful bacteria in the feces at 6, 11, and 15 wk of age and at 1-2 yr of age and determine if relative abundance of these bacteria correlates with vaccine responses shortly after vaccination (6, 11, 15 wk) and later in infancy (1-2 yr). As part of Aim 3 the "secretor status" genotype (FUT2 gene) of the mother will be determined from a cheek swab DNA sample.
- Conditions
- Vitamin A Deficiency
- Keywords
- Infant, Bangladesh, vitamin A, microbiota, vaccine, immunity
- Medical subject headings
- Vitamin A Deficiency
What is being measured
The primary outcome is the main question the study is designed to answer.
Naïve T-cells in peripheral blood
The concentration of naïve T-cells in peripheral blood will be measured once at 52 - 104 wk of age by flow cytometric analysis.
Measured: measured once at 52 - 104 weeks of age
Secondary outcomes (5)
Thymic output of naïve T cells
The thymic output of naïve T cells will be measured once at 52 - 104 wk of age by T-cell receptor excision circle (TREC) levels in DNA purified from peripheral blood mononuclear cells (PBMC).
Measured: measured once at 52 - 104 weeks of age
Immune response to vaccines
The immune responses to vaccines, measured at 52 - 104 wk of age, include: (A) Serum immunoglobulin G (IgG) and immunoglobulin A (IgA) responses to oral polio virus vaccine (OPV; given at birth, 6 wk, 10 wk, 14 wk); (B) serum IgG response to tetanus toxoid vaccine (TT; given at 6, 10 and 14 wk) and (C) Hepatitis B virus vaccine (HBV; given at 6, 10 and 14 wk); (D) the IgA response to OPV in stool; the (E) proliferative and (F) cytokine response of peripheral blood cluster of differentiation 4 (CD4) T-cells to OPV, TT, HBV vaccines and to the tuberculosis vaccine (BCG; given at birth). Antibody responses will be measured by ELISA, T-cell proliferation by flow cytometric analysis after 6 days of culture with corresponding vaccine antigens, and cytokines will be measured in supernatant after 3 and 6 d of culture with the same antigens.
Measured: Measured once at 52 - 104 weeks of age
Change in the relative abundance of stool bacteria
The relative abundance of stool bacteria will be measured using DNA extracts at four time points (6, 10 and 14 wk, and at one point between 52 and 104 wk) using culture-independent, next generation sequencing (NGS) of bacterial populations, followed by quantitative PCR (QPCR) and Bifidobacterium-specific terminal restriction-fragment-length polymorphism (TRFLP.)
Measured: 6, 10, 14 and 52-104 weeks of age
Serum Vitamin A status
Vitamin A status will be assessed by serum retinol or retinol binding protein (RBP4) at 52 - 104 wk of age.
Measured: measured once at 52-104 weeks of age
Secretor status of the study infant's mother.
The "secretor status" of the mother is determined by the FUT2 genotype. FUT2 is related to FUT1, the gene encoding fucosyltransferase 1, which determines the composition of specific glycans on erythrocytes that determine the ABO (or ABH) and Lewis blood group antigens. The activity of fucosyltransferase 2 (encoded by FUT2) causes the synthesis and secretion of these same glycans into breast milk and other secretions (e.g., saliva and other intestinal secretions).
Measured: measured once when infant is 52 - 104 weeks of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2014 (estimated)
- Study startOct 2014
- Primary completionSep 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Vitamin A DeficiencyStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 258 participants (actual)
Sponsor and investigators
- Lead sponsor
- USDA, Western Human Nutrition Research Center
- Sponsor type
- US federal agency
- Collaborators
- International Centre for Diarrhoeal Disease Research, Bangladesh, University of California, Davis, Thrasher Research Fund
- Responsible party
- Sponsor
- Investigators
- Charles B Stephensen, PhD, Principal investigator, USDA, Western Human Nutrition Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02027610
- Sponsor's protocol ID
- PR-13068
- Status last verified
- Nov 2015
- First submitted
- 23 Dec 2013
- Last updated
- 18 Nov 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Stephensen CB, Huda MN, Alam MJ, Khanam A, Afsar MNA, Raqib R, Qadri F, Peerson JM, Ahmad SM. Effects of neonatal Vitamin A supplementation on response to vaccinations in early infancy. Vaccine. 2026 Apr 30;80:128551. doi: 10.1016/j.vaccine.2026.128551. Epub 2026 Apr 4.
PubMed 41936264Ahmad SM, Huda MN, Raqib R, Qadri F, Alam MJ, Afsar MNA, Peerson JM, Tanumihardjo SA, Stephensen CB. High-Dose Neonatal Vitamin A Supplementation to Bangladeshi Infants Increases the Percentage of CCR9-Positive Treg Cells in Infants with Lower Birthweight in Early Infancy, and Decreases Plasma sCD14 Concentration and the Prevalence of Vitamin A Deficiency at Two Years of Age. J Nutr. 2020 Nov 19;150(11):3005-3012. doi: 10.1093/jn/nxaa260.
PubMed 32939553Ahmad SM, Raqib R, Huda MN, Alam MJ, Monirujjaman M, Akhter T, Wagatsuma Y, Qadri F, Zerofsky MS, Stephensen CB. High-Dose Neonatal Vitamin A Supplementation Transiently Decreases Thymic Function in Early Infancy. J Nutr. 2020 Jan 1;150(1):176-183. doi: 10.1093/jn/nxz193.
PubMed 31504694Huda MN, Ahmad SM, Kalanetra KM, Taft DH, Alam MJ, Khanam A, Raqib R, Underwood MA, Mills DA, Stephensen CB. Neonatal Vitamin A Supplementation and Vitamin A Status Are Associated with Gut Microbiome Composition in Bangladeshi Infants in Early Infancy and at 2 Years of Age. J Nutr. 2019 Jun 1;149(6):1075-1088. doi: 10.1093/jn/nxz034.
PubMed 31006815Huda MN, Ahmad SM, Alam MJ, Khanam A, Kalanetra KM, Taft DH, Raqib R, Underwood MA, Mills DA, Stephensen CB. Bifidobacterium Abundance in Early Infancy and Vaccine Response at 2 Years of Age. Pediatrics. 2019 Feb;143(2):e20181489. doi: 10.1542/peds.2018-1489.
PubMed 30674610
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Newborn Vitamin A Supplementation, Gut Microbiota and Vaccine Response During the Second Year of Life in Bangladeshi Infants
- ClinicalTrials.gov ID
- NCT02027610
- Acronym / sponsor ID
- PR-13068
- Conditions
- Vitamin A Deficiency
- Keywords
- Infant, Bangladesh, vitamin A, microbiota, vaccine, immunity
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 258 participants (actual)
- Lead sponsor
- USDA, Western Human Nutrition Research CenterUS federal agency
- Collaborators
- International Centre for Diarrhoeal Disease Research, Bangladesh, University of California, Davis, Thrasher Research Fund
- Study start
- Oct 2014
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 6 Jan 2014 (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.
Vitamin A deficiency (VAD) increases the risk of death from infections in infants and young children. The World Health Organization (WHO) recommends high-dose vitamin A supplementation (VAS) from 6-59 months of age to reduce the risk of death in countries where VAD is common. Such countries include Bangladesh, where this study is being conducted. While providing VAS at 6 months is recommended, providing VAS at birth may also decrease the risk of death since newborn infants are also at risk of VAD. VAS presumably reduces infant mortality by improving the immune response to infection and immunization. Vitamin A particularly affects the development and function of T cells, which develop in the thymus and are a key component of the memory response to infection and immunization. Vitamin A is important for development of an important class of T cells, regulatory T-cells, in the intestine. Regulatory T-cells prevent over-reaction of the immune system to substances the immune system might otherwise treat as harmful such as food or the healthy bacteria in the intestine. VAD could disrupt the normal colonization of the infant's intestinal tract and cause a condition called "dysbiosis" where abnormal bacteria flourish and adversely affect the infant's immune system. Dysbiosis may disrupt the immune response to injectable and oral vaccines. VAS at birth may prevent dysbiosis and thus improve immune function, response to vaccines, and child survival. The investigators recently completed an intervention trial in Bangladeshi infants (NCT01583972) examining the effect of VAS at birth on immune function and response to vaccines administered from birth to 14 wk of age. The present study will recruit infants who completed NCT01583972 when they are from 12 to 24 m of age to determine if VAS at birth affects the responses to these same vaccines when they are measured during the second year of life. The investigators will examine the effect of VAS at birth on gut microbiota measured early in infancy and during the second year of life, and explore the association of the gut microbiota with vaccine response. Mothers of study infants will participate in the study because the breast milk oligosaccharide content strongly affects gut microbiota composition and the "secretor status" of the mother, which can be determined from maternal FUT2 genotype, strongly affects breast milk oligosaccharide content.
Detailed description
Hypotheses and Specific Aims The investigators will test the hypotheses that VAS at birth will (1) improve production of new T cells at 1-2 yr of age; (2) improve T-cell memory responses at 1-2 yr of age to vaccines given early in infancy (birth - 14 wk); and (3) alter intestinal colonization early in infancy (6, 11 and 15 wk) and at 1-2 yr of age to increase Bifidobacterium and other healthy bacteria and decrease Proteobacteria and other harmful bacteria. Because the "secretor status" of the mother affects the carbohydrate content of the breastmilk, which can in turn affect Bifidobacterium growth in the infant gut, the "secretor status" of the mother will be determined. Furthermore these differences in composition of the intestinal bacteria will be associated with greater immunologic responses to oral and systemic vaccines.
Specific Aim 1: Determine if VAS or placebo at birth affect the blood concentration and thymic output of naïve T-cells at 1-2 yr of age. Specific Aim 2: Determine if VAS or placebo at birth affect T-cell mediated responses at 1-2 yr of age to vaccines given early in infancy, including serum and intestinal antibody levels, vaccine-specific proliferative responses by T cells and cytokine production by T cells. Specific Aim 3: Determine if VAS or placebo at birth affect the relative abundance of healthy intestinal bacteria and common harmful bacteria in the feces at 6, 11, and 15 wk of age and at 1-2 yr of age and determine if relative abundance of these bacteria correlates with vaccine responses shortly after vaccination (6, 11, 15 wk) and later in infancy (1-2 yr). As part of Aim 3 the "secretor status" genotype (FUT2 gene) of the mother will be determined from a cheek swab DNA sample.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 12 to 24 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- The present study will recruit infants who completed NCT01583972 when they are from 12 to 24 months of age. Mothers of these infants will also be recruited for collection of DNA from a cheek swab.
Key inclusion criteria (2 listed)
- for infant: completion of NCT01583972
- for mother: mother of study infant
Key exclusion criteria (1 listed)
- none
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Naïve T-cells in peripheral blood
Time frame: measured once at 52 - 104 weeks of age
The concentration of naïve T-cells in peripheral blood will be measured once at 52 - 104 wk of age by flow cytometric analysis.
5 secondary outcomes
Thymic output of naïve T cells
Time frame: measured once at 52 - 104 weeks of age
Immune response to vaccines
Time frame: Measured once at 52 - 104 weeks of age
Change in the relative abundance of stool bacteria
Time frame: 6, 10, 14 and 52-104 weeks of age
Serum Vitamin A status
Time frame: measured once at 52-104 weeks of age
Secretor status of the study infant's mother.
Time frame: measured once when infant is 52 - 104 weeks of age
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 18 Nov 2015.
- Derived from this study: PubMed 41936264Stephensen CB, Huda MN, Alam MJ, Khanam A, Afsar MNA, Raqib R, Qadri F, Peerson JM, Ahmad SM. Effects of neonatal Vitamin A supplementation on response to vaccinations in early infancy. Vaccine. 2026 Apr 30;80:128551. doi: 10.1016/j.vaccine.2026.128551. Epub 2026 Apr 4.
- Derived from this study: PubMed 32939553Ahmad SM, Huda MN, Raqib R, Qadri F, Alam MJ, Afsar MNA, Peerson JM, Tanumihardjo SA, Stephensen CB. High-Dose Neonatal Vitamin A Supplementation to Bangladeshi Infants Increases the Percentage of CCR9-Positive Treg Cells in Infants with Lower Birthweight in Early Infancy, and Decreases Plasma sCD14 Concentration and the Prevalence of Vitamin A Deficiency at Two Years of Age. J Nutr. 2020 Nov 19;150(11):3005-3012. doi: 10.1093/jn/nxaa260.
- Derived from this study: PubMed 31504694Ahmad SM, Raqib R, Huda MN, Alam MJ, Monirujjaman M, Akhter T, Wagatsuma Y, Qadri F, Zerofsky MS, Stephensen CB. High-Dose Neonatal Vitamin A Supplementation Transiently Decreases Thymic Function in Early Infancy. J Nutr. 2020 Jan 1;150(1):176-183. doi: 10.1093/jn/nxz193.
- Derived from this study: PubMed 31006815Huda MN, Ahmad SM, Kalanetra KM, Taft DH, Alam MJ, Khanam A, Raqib R, Underwood MA, Mills DA, Stephensen CB. Neonatal Vitamin A Supplementation and Vitamin A Status Are Associated with Gut Microbiome Composition in Bangladeshi Infants in Early Infancy and at 2 Years of Age. J Nutr. 2019 Jun 1;149(6):1075-1088. doi: 10.1093/jn/nxz034.
- Derived from this study: PubMed 30674610Huda MN, Ahmad SM, Alam MJ, Khanam A, Kalanetra KM, Taft DH, Raqib R, Underwood MA, Mills DA, Stephensen CB. Bifidobacterium Abundance in Early Infancy and Vaccine Response at 2 Years of Age. Pediatrics. 2019 Feb;143(2):e20181489. doi: 10.1542/peds.2018-1489.
- International Centre for Diarrhoeal Disease Research, BangladeshLink provided by the sponsor.
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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.
Charles B Stephensen, PhD principal investigator
USDA, Western Human Nutrition Research Center
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Vitamin A Deficiency, run by USDA, Western Human Nutrition Research Center at 3 sites in 2 countries.
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 2 inclusion and 1 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 18 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, 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?
Naïve T-cells in peripheral blood (time frame: measured once at 52 - 104 weeks of age). 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 NCT02027610, which also lists 5 linked publications.
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 18 Nov 2015.