Inflammatory Response In Schizophrenia

Phase 1

Completed

• Conditions: Schizophrenia
• Interventions: Drug: Natalizumab

• Registration Number: NCT03093064
• Lead Sponsor: King's College London

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 Timeline

• Study First Submitted: 2017-02-23
• Study First Submitted QC: 2017-03-22
• Study First Posted: 2017-03-28
• Study Start: 2017-04-01
• Primary Completion: 2023-06-15
• Study Completion: 2023-08-07
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-07
• Last Update Posted: 2024-03-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 66

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Patient Group: Natalizumab	Natalizumab	Natalizumab 300mg, intravenous, once monthly, total of 3 doses

Primary Outcome Measures

Name	Time	Method
Change in Translocator Protein (TSPO) availability pre- and post-natalizumab or placebo administration	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 Outcome Measures

Name	Time	Method
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).	Brain functional measures assessed using functional magnetic resonance imaging and magnetic resonance spectroscopy.; CSF inflammatory markers: measurements of cytokine concentrations (e.g. C-reactive protein, Interleukin-6)
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)	Both TSPO availability (as measured using PET imaging) and brain functional measures (as measured using functional magnetic resonance imaging and magnetic resonance spectroscopy) will be measured simultaneously using a combined PET/MRI scanner.
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).	Brain functional measures assessed using functional magnetic resonance imaging and magnetic resonance spectroscopy.; Blood inflammatory markers: measurements of cytokine concentrations (e.g. C-reactive protein, Interleukin-6)
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).	Both TSPO availability (as measured using PET imaging) and brain functional measures (as measured using functional magnetic resonance imaging and magnetic resonance spectroscopy) will be measured simultaneously using a combined PET/MRI scanner. There will be two separate scans - before and after administration of natalizumab/placebo.

Trial Locations

Locations (1)

Institute of Psychiatry, Psychology and Neuroscience, King's College London; 🇬🇧 London, United Kingdom