The PIMS Trial

  • Research type

    Research Study

  • Full title

    Psychosis Immune Mechanism Stratified Medicine Trial: The PIMS Trial

  • IRAS ID

    301682

  • Contact name

    Golam Khandaker

  • Contact email

    golam.khandaker@bristol.ac.uk

  • Sponsor organisation

    University of Birstol

  • ISRCTN Number

    ISRCTN23256704

  • Duration of Study in the UK

    2 years, 1 months, 31 days

  • Research summary

    Objective:
    Our primary objective is to test whether interleukin 6 (IL-6), a pro-inflammatory cytokine, contributes to pathogenesis of psychosis, and to examine potential mechanisms by which IL-6 affects psychotic symptoms, mood, cognition, and behaviour.

    Study Design and Procedure:
    We propose a proof-of-concept, randomised, parallel-group (1:1), double-blind, placebo-controlled study based on approximately 60 participants with psychosis who have evidence of low-grade inflammation (i.e., IL-6 ≥0.7pg/ml) and inflammation-related symptoms (i.e., anhedonia and amotivation). Participants will be randomised into two groups to receive single intravenous infusion of normal saline (placebo) or tocilizumab (a humanised monoclonal antibody that inhibits IL-6 signalling and is licensed in the UK for treatment of rheumatoid arthritis). Data on the primary outcome (i.e., anhedonia), other psychiatric measures, and blood samples will be collected at baseline and after infusion around day 7, 14, and 28. Cognitive and neuroimaging data will be collected at baseline and 14 days post-infusion. We will also recruit approximately 30 patients with psychosis without evidence of inflammation and 30 people with no history of mental illness. This allows for comparison of the baseline characteristics of inflammation-related psychosis.

    Study Population:
    With support from the Clinical Research Network, identification and recruitment of participants will be carried out from mental health services in England. Eligible participants will be aged 18-40 years, meet ICD-10 criteria for schizophrenia and related psychotic disorders (F20, F22, F25, F28, F29) within three years of first contact with psychiatric services (defined by acceptance to Early Intervention in Psychosis Services), able to provide informed consent, and meet other inclusion/exclusion criteria.

    Statistical Methods:
    We will compare change in primary outcome measure in the tocilizumab group with change in the placebo group, pre- and post-treatment. As a proof-of-concept study, we will focus on the overall pattern of change after tocilizumab infusion rather than individual tests for statistical significance.

  • REC name

    East of England - Cambridge East Research Ethics Committee

  • REC reference

    22/EE/0010

  • Date of REC Opinion

    2 Mar 2022

  • REC opinion

    Further Information Favourable Opinion