Inflammatory Response In Schizophrenia

NCT03093064 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 208083
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (4)

• 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 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 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).

Study Arms (2)

Patient Group: Natalizumab

EXPERIMENTAL

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

Drug: Natalizumab

Patient Group: Placebo

PLACEBO COMPARATOR

Saline, intravenous, once monthly, total of 3 doses

Other: Placebo: normal saline

Interventions

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.

Also known as: Tysabri

Patient Group: Natalizumab

Placebo: normal saline OTHER

Normal saline, intravenous infusion

Patient Group: Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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).
• Any absolute contraindications to natalizumab, as per natalizumab SPC
• Current or recent (last 3 months) infection, or history of significant infection, or an immunocompromised state
• Previous use of natalizumab or previous use of other monoclonal antibody.
• Ongoing long-standing use of oral steroids or non-steroidal anti-inflammatory drugs.
• Pregnancy and/or breast-feeding.
• Substance dependence/abuse other than to cigarettes.

Sponsors & Collaborators

• King's College London: lead
• South London and Maudsley NHS Foundation Trust: collaborator

Study Sites (1)

Institute of Psychiatry, Psychology and Neuroscience, King's College London

London, SE5 8AF, United Kingdom

Location

Related Publications (1)

• 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. 2025 Dec 1:awaf455. doi: 10.1093/brain/awaf455. Online ahead of print.

  PMID: 41326319 DERIVED

MeSH Terms

Conditions

Schizophrenia

Interventions

Natalizumab

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Oliver D Howes

  King's College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: February 23, 2017
• First Posted: March 28, 2017
• Study Start: April 1, 2017
• Primary Completion: June 15, 2023
• Study Completion: August 7, 2023
• Last Updated: March 8, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)