The Role of Inflammation in Brain and Cognitive Function in Mental Disorders
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- King's College London
- Enrollment
- 66
- Locations
- 1
- Primary Endpoint
- Change in Translocator Protein (TSPO) availability pre- and post-natalizumab or placebo administration
Study Overview
Brief Summary
Schizophrenia affects a significant proportion of the population and current levels of understanding of the illness is inadequate to treat it effectively. Converging lines of evidence suggest that neuroinflammation occurs in schizophrenia, and specifically over-activity of brain-resident immune cells called microglia. It is however unclear whether activated microglia play a primary role in schizophrenia, or whether this is a secondary phenomenon of no pathophysiological significance. The investigators therefore plan to test the effect of a monoclonal antibody (natalizumab) on psychotic symptoms in a cohort of first episode psychosis patients.
Detailed Description
One of the key aims of the study is to determine if there is a relationship between change in imaging inflammation markers from baseline to follow-up and changes in other markers of inflammation over the same period. In September 2021, an open label arm for natalizumab was added to the study. The relationship between changes in imaging inflammation markers and changes in other markers of inflammation will be analysed within subjects including all patients who received natalizumab.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 50 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Patient Group: Natalizumab
Natalizumab 300mg, intravenous, once monthly, total of 3 doses
Intervention: Natalizumab (Drug)
Outcomes
Primary Outcomes
Change in Translocator Protein (TSPO) availability pre- and post-natalizumab or placebo administration
Time Frame: Baseline TSPO availability will be assessed at day -14 prior to first administration of natalizumab/placebo (day zero). TSPO availability will be re-assessed post administration of natalizumab/placebo at day +57(+14 days)
TSPO availability assessed using Positron Emission Tomography (PET)
Secondary Outcomes
- Correlation of cerebrospinal fluid (CSF) inflammatory markers with brain functional measures at baseline.(Baseline PET/MRI scan will be performed at day -14 prior to administration of natalizumab/placebo (day zero). CSF collection will be performed between the time points day -14 to day -1 prior to administration of natalizumab/placebo (day zero).)
- Correlation of TSPO availability with brain functional measures at baseline.(Baseline combined PET/MRI scan will be performed at day -14 prior to administration of natalizumab/placebo (day zero))
- Correlation of blood inflammatory markers with brain functional measures at baseline.(Baseline PET/MRI scan will be performed at day -14 prior to administration of natalizumab/placebo (day zero). Blood collection will be performed between the time points day -14 to day -1 prior to administration of natalizumab/placebo (day zero).)
- Longitudinal change in TSPO availability correlated with longitudinal change in brain functional measures.(Baseline combined PET/MRI scan will be performed at day -14 prior to administration of natalizumab/placebo (day zero). Repeat combined PET/MRI scan will be performed at day +57(+14 days).)