Efficacy of Newborn Vitamin A Supplementation in Improving Immune Function

August 22, 2014 updated by: USDA, Western Human Nutrition Research Center
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
300

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

No older than 2 days (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Infant receiving OPV and BCG within 48 hr of birth

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Vitamin A
50,000 IU vitamin A in edible oil
Dietary supplement: retinyl palmitate
50,000 IU vitamin A in oil given within 48 h of birth from single-dose capsule
Other Names:
  • Vitamin A
Placebo Comparator: Placebo
edible oil used as diluent for vitamin A
Dietary supplement: Placebo
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Thymus size measured by ultrasound
Time Frame: through 15 wk of age
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
Time Frame: through 15 wk of age
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)
Time Frame: through 15 wk of age
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
Time Frame: through 15 wk of age
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
Time Frame: through 15 wk of age
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
Time Frame: through 15 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
Time Frame: through 15 wk of age
Bacterial lipopolysaccharide (LPS) concentrations will be measured in plasma as a marker of bacterial translocation.
through 15 wk of age

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
vitamin A status by modified, relative dose-response (MRDR) test
Time Frame: through 15 wk of age
vitamin A status will be measured using the MRDR in a subset of 30 subjects in each study arm.
through 15 wk of age
bulging fontanelle
Time Frame: 48 h after vitamin A dosing
The crainial fontanelle will be examined by study personnel to identify "bulging" as in indication of increased intracranial volume.
48 h after vitamin A dosing

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
USDA, Western Human Nutrition Research Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
International Centre for Diarrhoeal Disease Research, Bangladesh
World Health Organization

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Charles B. Stephensen, Ph.D., USDA, Western Human Nutrition Research Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 14, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 23, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 24, 2012

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 26, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 22, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • N3-TSA-003
  • PR-10012 (Other Identifier: icddr.b)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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