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| Name | Class |
|---|---|
| South London and Maudsley NHS Foundation Trust | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patient Group: Natalizumab | Experimental | Natalizumab 300mg, intravenous, once monthly, total of 3 doses |
|
| Patient Group: Placebo | Placebo Comparator | Saline, intravenous, once monthly, total of 3 doses |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Natalizumab | Drug | Natalizumab is a humanized monoclonal antibody against the cell adhesion molecule α4-integrin, currently licensed for the treatment of multiple sclerosis and Crohn's disease. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Translocator Protein (TSPO) availability pre- and post-natalizumab or placebo administration | TSPO availability assessed using Positron Emission Tomography (PET) | 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Correlation of TSPO availability with brain functional measures at baseline. | 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. | Baseline combined PET/MRI scan will be performed at day -14 prior to administration of natalizumab/placebo (day zero) |
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Inclusion criteria:
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Oliver D Howes | King's College London | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institute of Psychiatry, Psychology and Neuroscience, King's College London | London | SE5 8AF | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41326319 | Derived | Mizuno Y, Carreira Figueiredo I, Pillinger T, Hindley G, Baxter L, Parmar S, Lobo MC, Donocik JG, Rosenzweig I, Gupta A, Callegari I, Jeljeli S, Dunn JT, Hammers A, Awais R, Sander K, Arstad E, Politis M, Schubert JJ, Veronese M, Turkheimer FE, Reis Marques T, Howes OD. Immune alterations in schizophrenia and the effects of a therapeutic antibody: a neuroimaging study. Brain. 2026 Feb 7;149(2):620-631. doi: 10.1093/brain/awaf455. |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D000069442 | Natalizumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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This is an experimental medicine study, the purpose of which is provide a mechanistic understanding of neuroinflammation in schizophrenia by investigating response to natalizumab (phase 1b).
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|
| Placebo: normal saline | Other | Normal saline, intravenous infusion |
|
| Correlation of cerebrospinal fluid (CSF) inflammatory markers with brain functional measures at baseline. | 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) | 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 blood inflammatory markers with brain functional measures at baseline. | 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) | 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. | 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. | 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). |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |