An interventional study of retinyl palmitate and Placebo in Vitamin A Deficiency, sponsored by USDA, Western Human Nutrition Research Center. Completed at 1 site in Bangladesh. Open to participants aged Up to 48 Hours, including healthy volunteers. Per ClinicalTrials.gov, last updated 2014-08-26.
Sponsored by USDA, Western Human Nutrition Research Center · Not applicable, Interventional, and Prevention
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.
This project will examine the effect of vitamin A supplementation (50,000 IU) or placebo given with BCG and oral polio virus (OPV) immunization within 48 h of birth on immune function in 300 Bangladeshi infants (150 in each group) at risk of vitamin A deficiency recruited in a poor community of Dhaka, Bangladesh. Infants will be followed from birth through 15 wk of age. Current evidence from community-based mortality trials is not conclusive but suggests that such supplementation will decrease infant mortality from infectious disease through 6 m of age. The biological mechanism underlying this potential benefit is unclear but is presumed to include improving immune function. The investigators hypothesize that vitamin A supplementation at birth prevents vitamin A deficiency during a critical window of a few days to weeks when the immune system is first exposed to both normal, non-pathogenic organisms (e.g., commensal gut flora) and to potential pathogens. During this period the investigators propose that vitamin A supplementation will improve three aspects of immune function that will have sustained benefits throughout infancy: (1) normal thymus maturation and function; (2) development and mucosal targeting of adaptive immune responses, including regulatory T-cells (Treg), T-helper type 2 (Th2) cells, and IgA-secreting plasma cells and memory B-cells; and (3) mucosal barrier function. The three specific objectives of our project are: (1) Determine if vitamin A supplementation improves thymus maturation and function as indicated by ultrasonic analysis of thymus size and by analysis of thymic output of naïve T-cells using flow cytometric analysis of peripheral blood T-cells and by quantification of T-cell-receptor excision circles (TRECs) in peripheral blood. (2) Determine if vitamin A supplementation at birth alters (2.1) the T-cell response to BCG and OPV immunization assessed at 6 and 15 wk of age; (2.2) the T- and B-cell response to OPV immunization, assessed at 15 wk of age, and the secretory IgA response to OPV assessed at 6, 11 and 15 wk of age; and (2.3) the B-cell response to tetanus toxoid (TT) immunization, assessed at 15 wk of age. (3) Determine if vitamin A supplementation at birth will decrease bacterial lipopolysaccharide (LPS) concentrations in capillary blood, a marker of bacterial translocation.
67 studies on the registry are indexed under Vitamin A Deficiency; 7 are open to participants now.
This study's enrollment of 300 is above the median of 200 across 49 interventional studies indexed under Vitamin A Deficiency.
Browse Vitamin A Deficiency studies →USDA, Western Human Nutrition Research Center is the lead sponsor of 54 studies on the registry; 1 is open to participants now.
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Exclusion Criteria:
50,000 IU vitamin A in edible oil
Dietary Supplement: retinyl palmitate
edible oil used as diluent for vitamin A
Dietary Supplement: Placebo
50,000 IU vitamin A in oil given within 48 h of birth from single-dose capsule
Also known as: Vitamin A
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
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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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
Time frame: 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.
Time frame: through 15 wk of age
bacterial translocation to blood
Bacterial lipopolysaccharide (LPS) concentrations will be measured in plasma as a marker of bacterial translocation.
Time frame: through 15 wk of age
vitamin A status by modified, relative dose-response (MRDR) test
vitamin A status will be measured using the MRDR in a subset of 30 subjects in each study arm.
Time frame: through 15 wk of age
bulging fontanelle
The crainial fontanelle will be examined by study personnel to identify "bulging" as in indication of increased intracranial volume.
Time frame: 48 h after vitamin A dosing
The record gives a start of Jan 2012, a primary completion of Jul 2013 and a completion of Aug 2014. It does not say whether these dates are actual or estimated.
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This study is completed, as verified in Aug 2014. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Retinol palmitate
USDA, Western Human Nutrition Research Center