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A Study of Intranasal Live Attenuated Influenza Vaccine Immunogenicity and Associations With the Nasopharyngeal Microbiome Among Children in the Gambia (NASIMMUNE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02972957
Recruitment Status : Active, not recruiting
First Posted : November 25, 2016
Last Update Posted : March 11, 2019
Sponsor:
Collaborators:
University of Edinburgh
Public Health England
University of Oxford
National Institute for Public Health and the Environment (RIVM)
Information provided by (Responsible Party):
London School of Hygiene and Tropical Medicine

Brief Summary:

The live attenuated influenza vaccine (LAIV) is made up of weakened influenza viruses given into the nose and in early studies was shown to be better than the standard influenza vaccine at preventing infections in children. However, more recently, it has performed less well and it may also work less well in Sub-Saharan Africa. Not only do the investigators not know why this is, but the investigators also do not fully understand why LAIV produces stronger nasal antibody responses in some individuals but not others. Usually harmless bacteria that are present in participants noses can influence how our immune system works and variations in these may explain differences in how LAIV works. The project will recruit children given LAIV in the Gambia to gain further understanding of these issues.

The investigators will measure a variety of responses to LAIV, including genes that can change their expression early after vaccination and use advanced computational techniques to identify new relationships between these genes and other LAIV responses. The investigators will also see whether nasal bacterial profiles in children who respond to LAIV are different from those who do not. In addition, the investigators will alter these bacteria in a subset of children with antibiotics and see whether this affects both nasal gene expression and later responses to LAIV.


Condition or disease Intervention/treatment Phase
Influenza Biological: Nasovac-S Drug: Azithromycin Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 365 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Study of Intranasal Live Attenuated Influenza Vaccine Immunogenicity and Associations With the Nasopharyngeal Microbiome Among Children in the Gambia - The NASIMMUNE Study
Actual Study Start Date : January 30, 2017
Actual Primary Completion Date : December 19, 2018
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu Flu Shot

Arm Intervention/treatment
Experimental: LAIV-vaccinated group 1
Nasovac-S vaccination group A , blood samples days 0, 2, 21
Biological: Nasovac-S
one of 0.5ml intranasal dose of trivalent live attenuated vaccine (LAIV)

Experimental: LAIV-vaccinated group 2
Nasovac-S vaccination group B, blood samples at days 0, 7, 21
Biological: Nasovac-S
one of 0.5ml intranasal dose of trivalent live attenuated vaccine (LAIV)

No Intervention: Unvaccinated
control group C
Experimental: Oral Azithromycin & vaccination
group D - a single dose of oral Azithromycin will be given 28 days prior to Nasovac-S vaccination
Biological: Nasovac-S
one of 0.5ml intranasal dose of trivalent live attenuated vaccine (LAIV)

Drug: Azithromycin
a single dose of Azithromycin (liquid formulation - Zithromax) at 20mg/Kg (up to a maximum adult dose 1g) to be given to a subset of subjects
Other Name: Zithromax




Primary Outcome Measures :
  1. nasal IgA response [ Time Frame: 21 days post LAIV ]
    Influenza specific nasal IgA responses

  2. fold increase in oral fluid influenza-specific/total IgA ratio [ Time Frame: day 0 - Day 21 ]
  3. fold increase in oral fluid influenza-specific/total IgG ratio [ Time Frame: Day 0 - Day 21 ]

Secondary Outcome Measures :
  1. density of S. Pneumoniae [ Time Frame: day 7 and day 21 after LAIV compared to day 0 ]
    density of S. Pneumoniae before and after LAIV as established by quantitative PCR

  2. Changes in the relative abundance of different operational taxanomic units (OTUs) of nasopharyngeal microbiota [ Time Frame: day 7 and day 21 compared to day 0 in each participant ]
  3. gene expression changes in nasal and systemic samples [ Time Frame: 2 days after LAIV ]


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Ages Eligible for Study:   24 Months to 59 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • • Healthy male or female child at least 24 months of age and less than 60 months of age at the time of study entry.

    • Resident in the study area and with no plans to travel outside the study area during the period of subject participation.
    • Informed consent for the study participation obtained from a parent (or guardian only if neither parent is alive or if guardianship has been legally transferred (see section 11.2).
    • Willingness and capacity to comply with the study protocol as judged by a member of the clinical trial team.

Exclusion Criteria:

  • • Serious, active, medical condition, including but not limited to:

    • chronic disease of any body system
    • severe protein-energy malnutrition (weight-for-height Z-score of less than -3)
    • known genetic disorders, such as Down's syndrome or other cytogenetic disorder

      • Active wheezing
      • History of documented hypersensitivity to eggs or other components of the vaccine (including gelatin, sorbitol, lactalbumin and chicken protein), or with life-threatening reactions to previous influenza vaccinations.
      • History of documented hypersensitivity to macrolide antibiotics
      • History of Guillain-Barré syndrome.
      • Receipt of aspirin therapy or aspirin-containing therapy within the two weeks before planned study vaccination.
      • Any suspected or confirmed congenital or acquired state of immune deficiency including but not limited to primary immunodeficiencies including thymus disorders, HIV/AIDS, hematological or lymphoid malignancies (blood tests will not be routinely undertaken with this regard as part of the study).
      • Any current immunosuppressive/immunomodulatory treatment or receipt of any such treatment within the six months preceding trial enrolment (for corticosteroids this is defined as a dose of prednisolone (or equivalent) of greater than 2mg/kg/day for one week or 1mg/kg/day for one month. The use of topical corticosteroids is not an exclusion criterion.
      • The use of inhaled corticosteroids within the last one month.
      • Receipt of an influenza vaccine within the past 12 months.
      • Has any condition determined by investigator as likely to interfere with evaluation of the vaccine or be a significant potential health risk to the child or make it unlikely that the child would complete the study.
      • Any significant signs or symptoms of an acute illness or infection including:
    • an axillary temperature of 38.0°C or above or documented fever of 38°C or above in the preceding 14 days.
    • Any acute respiratory infection within 14 days of enrollment visit. If the reason for ineligibility is likely to be temporary (e.g. a fever of 38°C or above or acute respiratory infection) and either will or may resolve before the infant reaches 60 months, they will not be recorded as a screening failure but instead will be re-screened within an appropriate future time-window (e.g. at least 14 days after the last documented fever of 38°C or above or resolution of respiratory illness) and a decision made regarding eligibility at that point.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02972957


Locations
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Gambia
Medical Research Council unit The Gambia
Banjul, Gambia
Sponsors and Collaborators
London School of Hygiene and Tropical Medicine
University of Edinburgh
Public Health England
University of Oxford
National Institute for Public Health and the Environment (RIVM)

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: London School of Hygiene and Tropical Medicine
ClinicalTrials.gov Identifier: NCT02972957     History of Changes
Other Study ID Numbers: SCC 1502
First Posted: November 25, 2016    Key Record Dates
Last Update Posted: March 11, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by London School of Hygiene and Tropical Medicine:
intranasal
flu vaccine
Gambian children
Additional relevant MeSH terms:
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Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Azithromycin
Vaccines
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents