SchizophreniaPhase 1IRISNCT03093064
Inflammatory Response In Schizophrenia
A Phase 1 study testing Natalizumab in people with Schizophrenia, run by King's College London at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Natalizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 66 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Apr 2017to 7 Aug 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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;
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Institute of Psychiatry, Psychology and Neuroscience, King's College London
London, SE5 8AF
About this study
Official title: The Role of Inflammation in Brain and Cognitive Function in Mental Disorders
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.
Read the detailed 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.
- Conditions
- Schizophrenia
- Being tested
- Natalizumab, Placebo: normal saline
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NatalizumabDrug
Also called Tysabri
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.
Placebo: normal salineOther
Normal saline, intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Patient Group: Natalizumab | Experimental | Natalizumab 300mg, intravenous, once monthly, total of 3 doses Receives: Drug: Natalizumab |
| Patient Group: Placebo | Placebo comparator | Saline, intravenous, once monthly, total of 3 doses Receives: Other: Placebo: normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Translocator Protein (TSPO) availability pre- and post-natalizumab or placebo administration
TSPO availability assessed using Positron Emission Tomography (PET)
Measured: 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.
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.
Measured: 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.
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)
Measured: 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)
Measured: 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.
Measured: 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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2017
- Study start1 Apr 2017
- Primary completion15 Jun 2023
- Study completion7 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by King's College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- King's College London
- Sponsor type
- University, hospital or other
- Collaborators
- South London and Maudsley NHS Foundation Trust
- Responsible party
- Sponsor
- Investigators
- Oliver D Howes, Principal investigator, King's College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03093064
- Sponsor's protocol ID
- 208083
- Acronym
- IRIS
- Status last verified
- Mar 2024
- First submitted
- 23 Feb 2017
- Last updated
- 8 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 41326319
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Inflammation in Brain and Cognitive Function in Mental Disorders
- ClinicalTrials.gov ID
- NCT03093064
- Acronym / sponsor ID
- IRIS / 208083
- Conditions
- Schizophrenia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- King's College LondonUniversity, hospital or other
- Collaborators
- South London and Maudsley NHS Foundation Trust
- Study start
- 1 Apr 2017 (actual)
- Primary completion
- 15 Jun 2023 (actual)
- Study completion
- 7 Aug 2023 (actual)
- First posted
- 28 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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).
| Arm | Type | Receives |
|---|---|---|
| Patient Group: Natalizumab | Experimental | Drug: NatalizumabNatalizumab 300mg, intravenous, once monthly, total of 3 doses |
| Patient Group: Placebo | Placebo comparator | Other: Placebo: normal salineSaline, intravenous, once monthly, total of 3 doses |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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;
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NatalizumabAlso: TysabriNatalizumab is a humanized monoclonal antibody against the cell adhesion molecule α4-integrin, currently licensed for the treatment of multiple sclerosis and Crohn's disease. | Drug | Patient Group: Natalizumab |
| Placebo: normal salineNormal saline, intravenous infusion | Other | Patient Group: Placebo |
Primary outcome
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)
4 secondary outcomes
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)
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).
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).
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).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2024.
- Derived from this study: PubMed 41326319Mizuno 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Oliver D Howes principal investigator
King's College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Natalizumab in people with Schizophrenia, run by King's College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03093064, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2024; AzTrials last refreshed its copy on 2 Nov 2026.