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Sero-epidemiological Survey of England in 2019/2020 (STORY)

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ClinicalTrials.gov Identifier: NCT04061382
Recruitment Status : Recruiting
First Posted : August 19, 2019
Last Update Posted : December 22, 2020
Sponsor:
Information provided by (Responsible Party):
University of Oxford

Brief Summary:

This is a pilot study to assess the feasibility of establishing a national sero-epidemiological survey in England in individuals aged 0-24 years, focusing on assessing humoral immunity against diphtheria, Group C invasive meningococcus and SARS-CoV-2. The investigators will recruit 2800 to 3500 individuals, divided into two groups:

Group one (N= 2300):

This will include all age groups (0-24years), with recruitment restricted by postcodes provided by Public Health England (PHE) to recruit a representative population for the region as assessed by the IMD (Index of Multiple Deprivation scores).

Group two (N= up to 1200):

This group has been added following additional funding to enhance the sample size in response to the COVID-19 pandemic. This will recruit 0-19 year olds and will not be restricted by post code sampling. Instead recruitment will be by public promotion within the normal recruiting regions for each site.

Group three (N= up to 300):

Addition of Group 3 which is enhanced surveillance in participants from Black, Asian or minority ethnic groups (BAME). Since the start of recruitment we have noted that only 11% of participants are from BAME population, despite recruiting in ethnically diverse regions. Given the increased risk of COVID-19 disease in the BAME community, this is a potential limitation of the study as it stands, not only because it may not reflect the diversity of the UK population, but because it does not allow assessment of whether the differing disease rates and seropositivity in adults are reflected in differences in seropositivity rates in children. Similarly to Group 2, this will recruit 0-19 year olds and will not be restricted by post code sampling.


Condition or disease Intervention/treatment
Serogroup C Meningococcal Meningitis Diphtheria COVID-19 Procedure: Venepuncture Procedure: Oral fluid swab

Detailed Description:

Public Health England has an ongoing sero-prevalence programme to assess how well the population is protected from vaccine preventable diseases. The current way to check this is by testing left over blood samples from participating healthcare laboratories around the country. However, these samples may not be representative of the general population, particularly in younger age groups who are often most at risk from vaccine preventable diseases. In the Netherlands, they use a different system to assess how well the population is protected from vaccine preventable diseases, actively collecting blood samples from a representative cross section of society. This type of approach would address the limitations of using residual serum samples and allows the collection of additional relevant history e.g. number of family members and previous vaccines received. The investigators are therefore proposing a pilot study to assess the feasibility of establishing a national sero- epidemiological survey in England in individuals aged 0 - 24 years. The investigators will be focusing initially on diphtheria and group C invasive meningococcal disease, both of which are vaccine preventable. This will involve enrolling 2300 participants in the study from different geographical and socioeconomic backgrounds across our test sites and taking a blood sample. This blood will be analysed to look at the level of immunity to vaccine preventable diseases.

The original protocol has been amended to include the testing of antibodies against other infectious diseases, specifically COVID-19. A second group has been added to recruit an additional 500 to 1200 participants between the ages of 0-19 years. The additional funding has been used to open two more sites to recruit to group two across regions on England that are currently not represented by this study. Having a large number of blood samples from a range of age groups is useful when gathering information about an emerging disease such as the current novel coronavirus (COVID-19). These samples can help provide answers regarding the true number of infections with SARS-CoV-2 (the virus which causes COVID-19 disease) in this population. Group 2 can be enhanced by the samples received from other ethically approved research projects where participants have consented for their samples being used outside of the study.

Additional funding has been granted for the addition of 300 participants from the BAME community, who will form Group 3. Data from Group 3 would be invaluable in understanding whether higher rates of disease in the BAME community are a result of greater exposure to COVID-19 contact, a higher likelihood of being infected once exposed or a greater risk of disease once infection occurs.

In addition to increasing the sample size and the number of regions in the UK that are being sampled, a longitudinal sampling cohort has been introduced. A subset of participants equally distributed over the age bands will be enrolled into the longitudinal aspect of the study where repeat blood and saliva samples are taken to look for antibodies against SARS-CoV-2. A questionnaire to ascertain whether the participant or any household contacts have had any symptoms of or been tested positive for COVID-19 will also be collected.

A proportion of participants from this group from selected sites will also provide up to a maximum of three blood samples for separation of peripheral blood mononuclear cells (PBMCs) to evaluate T cell responses. These participants can be either seronegative or seropositive at their Visit 1.

With the latter addition of four more sites, all NHS regions are now represented in the study.

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Study Type : Observational
Estimated Enrollment : 3800 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: Serum Testing of Representative Youngsters: Sero- Epidemiological Survey of England in 2019/2020
Actual Study Start Date : October 15, 2019
Estimated Primary Completion Date : March 31, 2021
Estimated Study Completion Date : June 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diphtheria

Group/Cohort Intervention/treatment
Randomised selection of population - Group 1
Group 1 will be focusing on COVID-19, diphtheria and group C invasive meningococcal disease. The investigators are aiming to recruit around 2300 individuals and the investigators are aiming to ensure that sample is broadly representative of the region according to IMD (Index of Multiple Deprivation scores). PHE have generated a list of all postcodes in recruiting regions and determining the quintiles of IMD within that region. Participants interested in taking part in the study will contact sites to arrange a visits. Basic demographic characteristics will be collected by questionnaire and/ or case report form (CRF) and will include: DOB, gender, GP details, Ethnic group, association with communities of special interest, household income and vaccination history.The questionnaire will gather information regarding potential COVID-19 symptoms both in the participant and the participant's household.
Procedure: Venepuncture

One study visit will be conducted by research study staff and blood sampling will be carried out.

Up to three follow-up visits will be conducted for a percentage of participants, where additional blood samples will be collected. The blood sample will initially focus on looking at population immunity to diphtheria, group C invasive meningococcal disease and SARS-CoV-2.


Procedure: Oral fluid swab
Saliva sampling will be collected during the follow-up visits. This swab will be collected either by the participant or the participants parent/guardian on the day of the visit. The saliva sampling will primarily be analysed for SARS-CoV-2 antibodies.

Group 2

Group two will focus on 0-19 year olds only. They will not be restricted to the post code sampling. Instead this will include standard recruitment methods such as social media advertisements within the normal recruiting regions for each site. The questionnaire will gather information regarding potential COVID-19 symptoms both in the participant and the participant's household.

A proportion of participants from this group from selected sites will also provide up to a maximum of three blood samples for separation of peripheral blood mononuclear cells (PBMCs) to evaluate T cell responses. These participants can be either seronegative or seropositive at their Visit 1.

Procedure: Venepuncture

One study visit will be conducted by research study staff and blood sampling will be carried out.

Up to three follow-up visits will be conducted for a percentage of participants, where additional blood samples will be collected. The blood sample will initially focus on looking at population immunity to diphtheria, group C invasive meningococcal disease and SARS-CoV-2.


Procedure: Oral fluid swab
Saliva sampling will be collected during the follow-up visits. This swab will be collected either by the participant or the participants parent/guardian on the day of the visit. The saliva sampling will primarily be analysed for SARS-CoV-2 antibodies.

Group 3
Group three will consist of up to 300 participants aged 0-19 from the Black, Asian and Minority ethnic population aged 0-19 years. They will not be restricted to the post code sampling and will be recruited at a sub-set of sites depending on capacity and the demographic profile of the local population. Recruitment will be by multiple approaches, including mail outs and advertising in community (e.g. community centres, religious establishments) or GP practices where we have ethics approval for them to act as PICs. These can vary according to each site's experience and their contacts within their local community on how is best to approach the BAME community.
Procedure: Venepuncture

One study visit will be conducted by research study staff and blood sampling will be carried out.

Up to three follow-up visits will be conducted for a percentage of participants, where additional blood samples will be collected. The blood sample will initially focus on looking at population immunity to diphtheria, group C invasive meningococcal disease and SARS-CoV-2.


Procedure: Oral fluid swab
Saliva sampling will be collected during the follow-up visits. This swab will be collected either by the participant or the participants parent/guardian on the day of the visit. The saliva sampling will primarily be analysed for SARS-CoV-2 antibodies.




Primary Outcome Measures :
  1. Feasibility of developing an England based sero-epidemiological programme in 0-24 year olds [ Time Frame: 11months ]
    Measure the representativeness of participants as compared to the census data for the study region.

  2. Feasibility of developing an England based sero epidemiological survey in 0-24 year olds [ Time Frame: 11 months ]
    Test serological markers of immunity for vaccine preventable diseases starting with diphtheria.

  3. Feasibility of developing an England based sero epidemiological survey in 0-24 year olds [ Time Frame: 11 months ]
    Test serological markers of immunity for vaccine preventable diseases including Invasive Meningococcal type C.

  4. Feasibility of developing an England based sero epidemiological survey in 0-24 year olds [ Time Frame: 11 months ]
    Test serological markers to determine the true number of infections with SARS-CoV-2 in the population.


Secondary Outcome Measures :
  1. Recruitment rate [ Time Frame: 11 Months ]
    Recruitment rate per month, recruitment rates as percentage of potential participants contacted

  2. Cost [ Time Frame: 12 months ]
    Cost per sample obtained of 'disease specific correlates of protection/markers of immunity, e.g. Anti-Diphtheria Toxoid IgG concentrations and Capsular Group C meningococcal Serum bactericidal activity (SBA) titres and Serum IgG to SARS-CoV-2 antigens, including spike and nucleocapsid protein (as measured by ELISA and/or neutralising assay)

  3. To assess, in relevant age groups and different ethnicities antibody concentrations against infections and vaccine preventable diseases [ Time Frame: 11 months ]
    IgG to COVID-19 spike and nucleocapsid protein

  4. Sera collection [ Time Frame: 11 months ]
    • A collection of anonymised sera from participants with appropriate consent and known demographic details and immunisation history.
    • Serum IgG to SARS-CoV-2 antigens, including spike and nucleocapsid protein (as measured by ELISA and/or neutralising assay)

  5. Exploratory [ Time Frame: 11 months ]

    • Representativeness of participants sampled, in terms of the local population's ethnicity, community identity, migrant population and socioeconomic background between groups.

    Differences in immunological read outs

    • PCR for SARS-CoV-2 on saliva samples this will be stored and processed at the end of the study.
    • IgA to SARS-CoV-2 in saliva paired with serum samples.

  6. Exploratory [ Time Frame: 6 months ]

    • T cell responses to SARS-CoV-2 antigens including, but not limited to S, M and N proteins, as measured by techniques including, but not limited to

    • ELISpot
    • ICS
    • Proliferation assay

  7. Exploratory [ Time Frame: 6 months ]
    • Antigen specific IgG and T cells against non-SARS-CoV-2 coronaviruses (e.g. NL62 and 229E)


Biospecimen Retention:   Samples With DNA
Blood samples will be centrifuged, separated and frozen at local sites at -80°C. Ideally this will happen within 24h with a window of up to 72h. Up to two 2ml aliquots per participant will be shipped to PHE in batches of up to 500 on dry ice. Residual sera beyond this volume will be shipped to the Oxford Vaccine Group(OVG) for storage. For participants where consent is obtained for DNA extraction and storage in the Oxford Vaccine Centre biobank residual blood clots will be shipped to the OVG for this purpose. Participant or their parents will take the oral fluid swab on the day of the visit. Once received by the study team it will be kept in a cool bag until the samples arrive in the lab. They will then be frozen to -80° before being shipped to PHE. Blood samples collected for T cell testing will be shipped to the OVG lab for same-day processing for separation of PBMCs. Saliva samples with be processed in line with local SOPs


Information from the National Library of Medicine

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Ages Eligible for Study:   up to 24 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

Basic demographic characteristics will be collected by questionnaire and/or case report form (CRF) and will include: DOB, gender, GP details, ethnic group, association with communities of special interest (e.g. faith communities) household income and vaccination history.

Vaccination history will be verified during serum sample collection using the Red Book or other vaccination records, or checking with the general practitioner or the Child Health Immunisation Service (CHIS) database. Where possible this will include batch information for diphtheria pre-school booster to determine which specific product was received.

Criteria

Inclusion Criteria:

  • Parents/legal guardians or adult participant* is willing and able to give informed consent for participation in the study.
  • Male or Female, aged 0 - 24 years inclusive (Group 1)
  • Male or Female, aged 0 - 19 years inclusive (Group 2)
  • Male or Female, aged 0 - 19 years inclusive with BAME background (Group 3)
  • Parents/legal guardians or adult participants are willing to allow their General Practitioner or relevant NHS databases to be contacted for a full immunisation history

Exclusion Criteria:

  • If participants do not live in the postcode districts selected by PHE (Group 1 only)
  • If participants are not from the BAME population (Group 3 only
  • Medically diagnosed bleeding disorder
  • Medically diagnosed platelet disorder
  • Anticoagulation medication
  • Pregnancy
  • If another member of their household is participating who is within 5 years of age of the potential participants age

Temporary exclusion criteria:

The participant may not enter the study if they or any member of their household is under temporary isolation measures for suspected SARS-CoV-2 infection.


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): NCT04061382


Contacts
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Contact: Iason Vichos 01865611400 info@ovg.ox.ac.uk
Contact: Helen Rafcliffe, Dr 01865611400 info@ovg.ox.ac.uk

Locations
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United Kingdom
Centre for Clinical Vaccinology & Tropical Medicine (CCVTM) Recruiting
Oxford, Oxfordshire, United Kingdom, OX3 7LE
Contact: Iason Vichos    01865 611 400    info@ovg.ox.ac.uk   
Sponsors and Collaborators
University of Oxford
Investigators
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Principal Investigator: Matthew Snape, Professor University of Oxford
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Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT04061382    
Other Study ID Numbers: ID 263097
First Posted: August 19, 2019    Key Record Dates
Last Update Posted: December 22, 2020
Last Verified: December 2020
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
Additional relevant MeSH terms:
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Diphtheria
Meningitis, Meningococcal
Meningitis
Central Nervous System Diseases
Nervous System Diseases
Meningococcal Infections
Neisseriaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Corynebacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Meningitis, Bacterial
Central Nervous System Bacterial Infections
Central Nervous System Infections