Inflammatory Response In Schizophrenia (IRIS)

King's College London

Status and phase: Completed; Phase 1

Conditions: Schizophrenia

Treatments: Drug: Natalizumab; Other: Placebo: normal saline

Study type: Interventional

Funder types: Other

Identifiers

NCT03093064

208083

Details and patient eligibility

About

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.

Full 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.

Enrollment: 66 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Aged 18-50 years
2. Diagnosis of schizophrenia or other psychotic disorder (Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5);
3. Symptomatic, defined as one or more positive symptom >3 AND one or more negative symptom >3 on the Positive and Negative Syndrome Scale (PANSS);
4. No acute relapse and psychiatrically stable for >1 month before screening;

Exclusion criteria

1. History of significant co-morbid CNS disorder (including significant head trauma or significant loss of consciousness, Parkinson's Disease, Epilepsy, Alzheimer's Dementia, Huntington's Disease).
2. Any absolute contraindications to natalizumab, as per natalizumab SPC
3. Current or recent (last 3 months) infection, or history of significant infection, or an immunocompromised state
4. Previous use of natalizumab or previous use of other monoclonal antibody.
5. Ongoing long-standing use of oral steroids or non-steroidal anti-inflammatory drugs.
6. Pregnancy and/or breast-feeding.
7. Substance dependence/abuse other than to cigarettes.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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66 participants in 2 patient groups, including a placebo group

Patient Group: Natalizumab

Experimental group

Description:

Natalizumab 300mg, intravenous, once monthly, total of 3 doses

Treatment:

Drug: Natalizumab

Patient Group: Placebo

Placebo Comparator group

Description:

Saline, intravenous, once monthly, total of 3 doses

Treatment:

Other: Placebo: normal saline