IRMA

  • Research type

    Research Study

  • Full title

    Investigation of the Role of Microbiota in Arthritic Inflammation in DMARD-naïve Early Arthritis Patients

  • IRAS ID

    208324

  • Contact name

    Michele Bombardieri

  • Contact email

    m.bombardieri@qmul.ac.uk

  • Sponsor organisation

    QMUL

  • Duration of Study in the UK

    3 years, 0 months, 1 days

  • Research summary

    Based on the current understanding in the field, we hypothesise that certain oral and gut bacterial species play a critical role in causing and perpetuating RA. Also, there are reports linking periodontitis and RA. To test our hypothesis, we will use samples from recently diagnosed, treatment-naïve RA patients with periodontitis. As controls, we will utilise samples from participants who have periodontitis, but do not have arthritis, as well as samples from patients with arthritis, but no periodontitis. Using these precious samples, we aim to:
    • determine the link between certain oral and gut bacterial species and inflammation in synovium and periodontal tissue as potential “initiating” sites where inflammation is triggered,
    • identify the bacterial culprits by analysing which bacteria are targeted by antibodies produced in patients’ diseased tissues,
    • demonstrate that these bacteria can indeed cause arthritic inflammation using mouse models.

    Moreover, by monitoring changes in the presence of bacterial products, antibodies and bacteria over time in correlation with the worsening or improvement of arthritis, we aim to
    • identify factors that can either drive arthritic disease or enable resolution of inflammation and
    • determine biomarkers for response to current conventional therapies for RA.
    In this context, we want to characterise and compare the early phases and the progression of arthritic inflammation between patients with either both RA and periodontitis or RA but no periodontitis.
    Lay summary of study results: A total of 17 patients were recruited to this study between September 2017 and September 2021. One Serious Adverse Event was reported for one patient in the study; however, this was unrelated to the study procedures.
    9 patients had a synovial biopsy as part of the study, and 3 of these patients had a second synovial biopsy after 24 weeks. 13 oral biopsies were collected (9 at baseline, 4 at week 24).40 study bloods (16 at baseline, 11 at week 12, 1 at week 18, 12 at week 24)., 34 oral samples (15 at baseline, 10 at week 12 and 9 at week 24), 28 saliva samples (14 at baseline, 8 at week 12 and 6 at week 24),23 stool samples were collected (14 at baseline, 3 at week 12 and 6 at week 24) and 9 urine samples at baseline. These samples have now been transferred to the EMR Biobank for future research.

    This study was heavily impacted by Covid-19. The experimental work as stated in the original plan of investigation and in line with the original study objectives is planned to start imminently on the biological samples collected with additional funding successfully obtained from the Barts Charity. . The findings will be disseminated once these additional analyses will be completed.

  • REC name

    London - City & East Research Ethics Committee

  • REC reference

    16/LO/2076

  • Date of REC Opinion

    15 Dec 2016

  • REC opinion

    Favourable Opinion