NCT02027610

Brief 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. 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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
258

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Oct 2014

Shorter than P25 for all trials

Geographic Reach
2 countries

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 23, 2013

Completed
14 days until next milestone

First Posted

Study publicly available on registry

January 6, 2014

Completed
9 months until next milestone

Study Start

First participant enrolled

October 1, 2014

Completed
11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2015

Completed
Last Updated

November 18, 2015

Status Verified

November 1, 2015

Enrollment Period

11 months

First QC Date

December 23, 2013

Last Update Submit

November 17, 2015

Conditions

Vitamin A Deficiency

Keywords

InfantBangladeshvitamin Amicrobiotavaccineimmunity

Outcome Measures

Primary Outcomes (1)

  • 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 once at 52 - 104 weeks of age

Secondary Outcomes (5)

  • Thymic output of naïve T cells

    measured once at 52 - 104 weeks of age

  • Immune response to vaccines

    Measured once at 52 - 104 weeks of age

  • Change in the relative abundance of stool bacteria

    6, 10, 14 and 52-104 weeks of age

  • Serum Vitamin A status

    measured once at 52-104 weeks of age

  • Secretor status of the study infant's mother.

    measured once when infant is 52 - 104 weeks of age

Eligibility Criteria

Age12 Months - 24 Months
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)
Sampling MethodNon-Probability Sample
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.

You may qualify if:

  • for infant: completion of NCT01583972
  • for mother: mother of study infant

You may not qualify if:

  • none

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

University of California, Davis

Davis, California, 95616, United States

Location

USDA Western Human Nutrition Research Center

Davis, California, 95616, United States

Location

International Centre for Diarrhoeal Disease Research, Bangladesh

Dhaka, 1212, Bangladesh

Location

Related Publications (4)

  • Ahmad 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.

    PMID: 32939553DERIVED

  • Ahmad 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.

    PMID: 31504694DERIVED

  • Huda 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.

    PMID: 31006815DERIVED

  • Huda 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.

    PMID: 30674610DERIVED

Related Links

Biospecimen

Retention: SAMPLES WITH DNA

Infant specimens containing DNA isolated from periferal blood mononuclear cells (PBMC) will be retained for future analyses. Maternal specimens containing DNA from cheek swabs will be retained for future analyses.

MeSH Terms

Conditions

Vitamin A Deficiency

Condition Hierarchy (Ancestors)

AvitaminosisDeficiency DiseasesMalnutritionNutrition DisordersNutritional and Metabolic Diseases

Study Officials

  • Charles B Stephensen, PhD

    USDA, Western Human Nutrition Research Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
CROSS SECTIONAL
Sponsor Type
FED
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 23, 2013

First Posted

January 6, 2014

Study Start

October 1, 2014

Primary Completion

September 1, 2015

Study Completion

September 1, 2015

Last Updated

November 18, 2015

Record last verified: 2015-11

Locations

BA(1)US(2)