CAR-CF: COVID-19 Antibody Responses In Cystic Fibrosis

Sponsor
Queen's University, Belfast (Other)
Overall Status
Recruiting
CT.gov ID
NCT04863573
Collaborator
Cystic Fibrosis Foundation (Other)
1,000
11
29.4
90.9
3.1

Study Details

Study Description

Brief Summary

Coronavirus disease 2019 (COVID-19) which is caused by the virus SARS-CoV-2 has resulted in an ongoing global pandemic. It is unclear whether the relatively low number of reported cases of COVID-19 in people with CF (pwCF) is due to enhanced infection prevention practices or whether pwCF have protective genetic/immune factors. This study aims to prospectively assess the proportion of pwCF, including both adults and children with CF who have evidence of SARS-CoV-2 antibodies over a two-year period. This study will also examine whether pwCF who have antibodies for SARS-CoV-2 have a different clinical presentation and what impact this has on their CF disease. The proposed study will recruit pwCF from paediatric and adult CF centres throughout the United Kingdom. Serological testing to detect antibodies will be performed on blood samples taken at month 0, 6, 12, 18 and 24 with additional time-points if bloodwork is available via normal clinical care. Clinical data on, lung function, CF-related medical history, pulmonary exacerbations, antibiotic use, and microbiology and vaccination receipt, will be collected during routine clinical assessments.

Associations will be examined between socio-demographic and clinical variables and serologic testing. The effects of SARS-CoV-2 infection on clinical outcomes and analyse end-points will be examined to explore any age-related or gender-based differences, as well as subgroup analysis of outcomes in lung-transplant recipients and pwCF receiving CFTR modulator therapies. As pwCF receive COVID-19 vaccination a comparison of the development and progression of anti-SARS-CoV-2 antibodies in pwCF following natural infection and vaccination SARS-CoV-2 over time will be performed.

Condition or Disease Intervention/Treatment Phase

    Detailed Description

    This is a prospective, longitudinal cohort study in people with Cystic Fibrosis (pwCF) that involves repeated serial sampling of participants. This study design was chosen to provide comprehensive information on SARS-CoV-2 seroprevalence changes over time and the subsequent clinical impact on pwCF. The study will be conducted at participating CF centres over a 3-year period. Study participants will include paediatric and adult pwCF. For the UK section of the study, UK investigators in the European Cystic Fibrosis Society-Clinical Trials Network (ECFS-CTN) will be invited to participate. Participating investigators can enrol all eligible pwCF over a 12-month period. Participants are then followed up for 24 months. Participants will donate blood samples at their routine clinic visits. Blood samples will be collected at Day 0 (baseline), at Months 6, 12, 18 and 24 (to coincide with routine clinical reviews). Additional blood samples will be taken opportunistically every time the participant visits the clinic for blood draws. These blood samples could be related to, routine care, annual review visits, pulmonary exacerbations (PEx), CF complications or when initiating new treatments (e.g. CFTR modulators).

    Serum from blood samples will be shipped to a central laboratory (Queen's University Belfast) for standardized measurement of SARS-CoV-2 antibodies.

    Alongside the blood samples the investigators will also collect clinical data from the patient's health records and will input this data into the case report form (CRF). Clinical data will be collected in conjunction with routine care visits, according to local clinical practice. Investigators will collect data elements from information routinely recorded in the patients' medical records. Data will be collected at baseline, month 6, 12, 18 and 24 as per the study schedule, and at additional blood sampling timepoints as previously explained above. Data collection will include routine data available from CF clinic follow-ups including background demographic information, CF medical history, medications, exacerbation information, sputum microbiology and clinical and lung function parameters. Information on SARS-CoV-2 infection history and vaccine receipt will also be collected.

    The maximum follow-up duration of participation in the study for each patient will be 24 months. This study duration (24-month follow-up) is justified as it provides sufficient time to observe changes in antibody prevalence over the course of the COVID-19 pandemic as well as sufficient time to determine long term clinical outcomes for pwCF who are SARS-CoV-2 seropositive. Furthermore, we anticipate the 2-year study follow-up period will provide sufficient time to observe the impact of vaccination on antibody levels given that a number of vaccines are now commercially available.

    The investigators will compare the level of antibody responses between natural COVID-19 infection and vaccination in pwCF and how this varies over time. This will be achieved by analyzing seroprevalence and antibody levels according to natural infection and vaccination status and according to time of sample post infection or post vaccination, if known.

    Optional Study sample collection:

    For participants who consent, a second blood sample will also be drawn into EDTA tubes (plasma). Consent to this optional study sample would allow this sample and any remaining serum (following antibody testing) to be stored for future analysis and allow further research to be carried out on related studies to COVID-19 and CF.

    Study Design

    Study Type:
    Observational
    Anticipated Enrollment :
    1000 participants
    Observational Model:
    Cohort
    Time Perspective:
    Prospective
    Official Title:
    COVID-19 Antibody Responses In Cystic Fibrosis: CAR-CF
    Actual Study Start Date :
    Nov 19, 2021
    Anticipated Primary Completion Date :
    May 1, 2024
    Anticipated Study Completion Date :
    May 1, 2024

    Outcome Measures

    Primary Outcome Measures

    1. SARS-COV-2 seroprevalence [3-year period (comprising a 1-year enrollment period and a 2-year follow-up)]

      proportion of pwCF with at least 1 seropositive result over the study period and the difference in this proportion by age, geographical area and over time.

    2. Association of SARS-CoV-2 seropositivity, clinical symptoms and clinical outcomes in pwCF [3-year period (comprising a 1-year enrollment period and a 2-year follow-up)]

      incidence of symptomatic COVID-19 over the study period and severity; proportion of seropositive pwCF with subsequent CF exacerbation compared to pwCF who are seronegative; death rate in pwCF with at least one seropositive result compared to pwCF who are seronegative.

    3. Longitudinal comparison of the detection of anti-SARS-CoV-2 antibodies in pwCF following natural infection and SARS-CoV-2 vaccination. [3-year period (comprising a 1-year enrollment period and a 2-year follow-up)]

      Measuring detectable antibody levels for each study participant at baseline and at each study time point including 6,12, 18 and 24 months post enrollment with additional samples if participant has blood drawn for other clinical care reason.

    Secondary Outcome Measures

    1. Serum proteomic and genomic responses of pwCF who are SARS-CoV-2 seropositive and seronegative. [anticipated 5-10 years]

      Measuring detectable proteomic and genomic responses in pwCF according to serostatus (positive or negative for antibodies) as well as according to natural infection versus vaccination

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    All
    Inclusion Criteria:

    • Consenting people with cystic fibrosis of any age, genotype, transplant status and disease severity

    Exclusion Criteria:
    • Refusal to give informed consent

    • Contraindication to venepuncture.

    Participants already enrolled in a clinical trial are eligible for enrollment in this study. Inclusion in CAR-CF should not preclude enrollment in other observational clinical trial studies or clinical trials of an investigational medicinal product (CTIMP).

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University Hospital Southampton Nhs Foundation Trust Southampton Engladn United Kingdom SO16 6YD
    2 University Hospitals Birmingham Nhs Foundation Trust Birmingham England United Kingdom B15 2GW
    3 Birmingham Women'S and Children'S Nhs Foundation Trust Birmingham England United Kingdom B4 6NH
    4 Leeds Teaching Hospitals Nhs Trust Leeds England United Kingdom LS9 7TF
    5 King'S College Hospital Nhs Foundation Trust London England United Kingdom SE5 9RS
    6 Royal Brompton & Harefield Nhs Foundation Trust London England United Kingdom SW3 6NP
    7 Nottingham University Hospitals Nhs Trust Nottingham England United Kingdom NG7 2UH
    8 Queens University Belfast Belfast Northern Ireland United Kingdom
    9 NHS Greater Glasgow and Clyde Glasgow Scotland United Kingdom G12 0XH
    10 Cardiff & Vale University Lhb Cardiff Wales United Kingdom CF14 4HH
    11 Cardiff & Vale University Lhb Cardiff Wales United Kingdom

    Sponsors and Collaborators

    • Queen's University, Belfast
    • Cystic Fibrosis Foundation

    Investigators

    • Principal Investigator: Damian Downey, Queens University Belfast

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Damian Downey, Clinical Senior Lecturer, Queen's University, Belfast
    ClinicalTrials.gov Identifier:
    NCT04863573
    Other Study ID Numbers:
    • B21/07
    First Posted:
    Apr 28, 2021
    Last Update Posted:
    Feb 1, 2022
    Last Verified:
    Jan 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Feb 1, 2022