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Inflammatory Response In Schizophrenia (IRIS)

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ClinicalTrials.gov Identifier: NCT03093064
Recruitment Status : Active, not recruiting
First Posted : March 28, 2017
Last Update Posted : August 18, 2017
Sponsor:
Collaborator:
South London and Maudsley NHS Foundation Trust
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Schizophrenia Drug: Natalizumab Other: Placebo: normal saline Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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).
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: The Role of Inflammation in Brain and Cognitive Function in Mental Disorders
Actual Study Start Date : April 1, 2017
Estimated Primary Completion Date : April 1, 2022
Estimated Study Completion Date : April 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia
Drug Information available for: Natalizumab

Arm Intervention/treatment
Experimental: Patient Group: Natalizumab Drug: 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.
Other Name: Tysabri

Placebo Comparator: Patient Group: Placebo Other: Placebo: normal saline
Normal saline, intravenous infusion




Primary Outcome Measures :
  1. Change in Translocator Protein (TSPO) availability pre- and post-natalizumab or placebo administration [ Time Frame: 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 :
  1. Correlation of TSPO availability with brain functional measures at baseline. [ Time Frame: 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.

  2. Correlation of cerebrospinal fluid (CSF) inflammatory markers with brain functional measures at baseline. [ Time Frame: 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)


  3. Correlation of blood inflammatory markers with brain functional measures at baseline. [ Time Frame: 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)


  4. Longitudinal change in TSPO availability correlated with longitudinal change in brain functional measures. [ Time Frame: 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.



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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03093064


Locations
United Kingdom
Institute of Psychiatry, Psychology and Neuroscience, King's College London
London, United Kingdom, SE5 8AF
Sponsors and Collaborators
King's College London
South London and Maudsley NHS Foundation Trust
Investigators
Principal Investigator: Oliver D Howes King's College London

Responsible Party: King's College London
ClinicalTrials.gov Identifier: NCT03093064     History of Changes
Other Study ID Numbers: 208083
First Posted: March 28, 2017    Key Record Dates
Last Update Posted: August 18, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Natalizumab
Immunologic Factors
Physiological Effects of Drugs