Clinical trial
The Role of Inflammation in Brain and Cognitive Function in Mental Disorders
Name
208083
Description
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.
Trial arms
Trial start
2017-04-01
Estimated PCD
2023-06-15
Trial end
2023-08-07
Status
Completed
Phase
Early phase I
Treatment
Natalizumab
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.
Arms:
Patient Group: Natalizumab
Other names:
Tysabri
Placebo: normal saline
Normal saline, intravenous infusion
Arms:
Patient Group: Placebo
Size
66
Primary endpoint
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)
Eligibility criteria
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.
Protocol
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Updated at
2024-03-08
1 organization
Organization
King's College London