Efficacy of Newborn Vitamin A Supplementation in Improving Immune Function

NCT01583972 | Completed DMC

• 2 other identifiers: N3-TSA-003PR-10012
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

Vitamin A supplementation at birth may increase survival of infants through one year of age by reducing mortality from infectious diseases, though current studies are not conclusive on this point. The goal of our study is to determine if supplementation of newborn infants with 50,000 IU of vitamin A improves aspects of immune function that may be impaired by vitamin A deficiency. Our underlying assumption is that supplementation may thus decrease risk of death by improving immune function and the ability to survive infections. This project will be limited to the examination of the impact of vitamin A on immune function and will not aim to determine the impact on morbidity or mortality, which would require larger sample sizes. The hypotheses addressed by this study are as follows: Provision of vitamin A supplements to newborns at risk of vitamin A deficiency will (1) improve functioning of the thymus (the source of T lymphocytes, cells of the immune system that are important in response to infection and immunization); (2) enhance T lymphocyte-mediated responses to standard vaccines given at birth and early in infancy; and (3) improve gut barrier function (i.e., ability to prevent bacterial infection across the epithelial barrier), relative to provision of a placebo.

Conditions

Vitamin A Deficiency

Keywords

Vitamin A deficiency; Vitamin A; retinyl palmitate; malnutrition; vaccine; vaccination; BCG; tuberculosis; polio virus; tetanus toxoid; hepatitis B virus; thymus; T lymphocyte; B lymphocyte; antibody; bacterial translocation; T-cell receptor excision circle

Outcome Measures

Primary Outcomes (7)

• Thymus size measured by ultrasound

  Thymus size will be assessed sonographically using a validated method in which the transverse diameter of the thymus and the sagittal area of its largest lobe are multiplied to give a volume-related thymic index (TI). This index has been shown to correlate with thymus weight and has been used to show that the human thymus is sensitive to environmental influences during infancy.

  through 15 wk of age

• peripheral blood naive T-helper lymphocyte concentration

  Naive and memory CD4 T lymphocytes will be measured by flow cytometric analysis using the CD45RA and CD45RO markers to identify naive and memory CD4+ T-cells, respectively. Naive T cells develop in the thymus and their level in peripheral blood is an index of thymic function.

  through 15 wk of age

• T-cell receptor excision circle (TREC) level in peripheral blood mononuclear cells (PBMC)

  Thymic T-cell production can be assessed by measuring signal-joint T cell receptor excision circles (TRECs) as a traceable molecular marker in newly produced naive T-cells. Thus, the content of TRECs in peripheral blood is an indicator of thymopoiesis or newly synthesized and exported naive T-cells. TREC assessment will be conducted in the stored peripheral blood mononuclear cells (PBMC) isolated from infant's blood by standard Ficoll density gradient methods.

  through 15 wk of age

• T-cell response to BCG (Bacillus Calmette-Guérin; to protect against tuberculosis) and oral polio virus (OPV) immunization

  The Flow-cytometric Assay of Specific Cell-mediated Immune response in Activated whole blood (FASCIA) will be used on peripheral blood mononuclear cells to determine the percentage of CD4+ T cells that that are responsive to the BCG and OPV vaccines given at birth (OPV is given again at 6, 10 and 14 wk of age). The BCG response will be elicited using purified protein derivative of M. tuberculosis and the OPV response using formalin-inactivated polio virus antigen (types 1, 2 and 3).

  through 15 wk of age

• Antibody response to oral polio virus (OPV) immunization

  The antibody in lymphocyte supernatant (ALS) assay will be used to assess the production of polio-specific antibody by peripheral blood mononuclear cells (PBMC) at 15 wk of age and the secretory IgA response to OPV will be assessed at 6, 11 and 15 wk of age by measuring antibody in stool

  through 15 wk of age

• T-cell and antibody response to tetanus toxoid (TT) and hepatitis B virus (HBV) vaccinations given at 6, 10 and 14 wk of age

  The Flow-cytometric Assay of Specific Cell-mediated Immune response in Activated whole blood (FASCIA) will be used to measure the T-cell response to TT and HBV immunization using these vaccine antigens to stimulate a response at 6 and 15 wk of age. The antibody in lymphocyte supernatant assay (ALS) will be used to measure the antibody responses to these vaccines at 15 wk of age.

  through 15 wk of age

• bacterial translocation to blood

  Bacterial lipopolysaccharide (LPS) concentrations will be measured in plasma as a marker of bacterial translocation.

  through 15 wk of age

Secondary Outcomes (2)

• vitamin A status by modified, relative dose-response (MRDR) test

  through 15 wk of age

• bulging fontanelle

  48 h after vitamin A dosing

Study Arms (2)

Vitamin A

EXPERIMENTAL

50,000 IU vitamin A in edible oil

Dietary Supplement: retinyl palmitate

Placebo

PLACEBO COMPARATOR

edible oil used as diluent for vitamin A

Dietary Supplement: Placebo

Interventions

retinyl palmitate DIETARY_SUPPLEMENT

50,000 IU vitamin A in oil given within 48 h of birth from single-dose capsule

Also known as: Vitamin A

Vitamin A

Placebo DIETARY_SUPPLEMENT

edible oil used as diluent for vitamin A given within 48 h of birth from single-dose capsule identical in appearance to vitamin A capsule

Placebo

Eligibility Criteria

• Age: Up to 48 Hours
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Infant receiving OPV and BCG within 48 hr of birth

You may not qualify if:

• Mother is less than 18 years of age
• Infant is part of a multiple birth
• Infant will likely not remain in the study area for the next 4 months
• Infant has a condition precluding vaccination
• Infant is unable to breastfeed or drink other fluids
• Birth weight is less than 1.5 kg

Sponsors & Collaborators

• USDA, Western Human Nutrition Research Center: lead
• International Centre for Diarrhoeal Disease Research, Bangladesh: collaborator
• World Health Organization: collaborator

Study Sites (1)

International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b)

Dhaka, 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: 32939553 DERIVED

• 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: 31504694 DERIVED

• 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: 30674610 DERIVED

• Ahmad SM, Raqib R, Qadri F, Stephensen CB. The effect of newborn vitamin A supplementation on infant immune functions: trial design, interventions, and baseline data. Contemp Clin Trials. 2014 Nov;39(2):269-79. doi: 10.1016/j.cct.2014.09.004. Epub 2014 Sep 28.

  PMID: 25269669 DERIVED

MeSH Terms

Conditions

Vitamin A Deficiency; Malnutrition; Tuberculosis; Tetanus; Hepatitis B

Interventions

retinol palmitate; Vitamin A

Condition Hierarchy (Ancestors)

Avitaminosis; Deficiency Diseases; Nutrition Disorders; Nutritional and Metabolic Diseases; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Clostridium Infections; Blood-Borne Infections; Communicable Diseases; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors

Study Officials

• Charles B. Stephensen, Ph.D.

  USDA, Western Human Nutrition Research Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2012
• First Posted: April 24, 2012
• Study Start: January 1, 2012
• Primary Completion: July 1, 2013
• Study Completion: August 1, 2014
• Last Updated: August 26, 2014

Record last verified: 2014-08

Locations

BA (1)