Treatment-resistant SchizophreniaEarly Phase 1RESTORENCT06270108
The Role of Glutamatergic Function in the Pathophysiology of Treatment-resistant Schizophrenia
A Early Phase 1 study testing Riluzole in people with Treatment-resistant Schizophrenia and Treatment-responsive Schizophrenia, run by King's College London at 1 site in United Kingdom.
Trial summary
The goal of this basic science study is to to explore the responsivity of glutamate in the brain of treatment-resistant schizophrenia patients to the drug riluzole. The main aims of the study are: To assess the role of glutamate in treatment-resistant schizophrenia using magnetic resonance spectroscopy. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Treatment-resistant Schizophrenia, Treatment-responsive Schizophrenia, Healthy Controls
- What is being tested?
- Riluzole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 288 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 14 Nov 2022to 31 Dec 2024
- Phase
- Early 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Aged 18 years old or older;
- No diagnosis of schizophrenia, schizophreniform or any psychotic disorder;
- Sufficient understanding of the nature of the study and any hazards of participating in it;
- Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of the entire study;
- Willingness to give written consent to participate after reading the information and consent form, and after having the opportunity to discuss the study with the investigator or his delegate;
- Capacity to provide informed consent, as judged by an investigator.
Who cannot join
- Co-morbid psychiatric or other CNS disorder;
- Family history of Schizophrenia or Psychotic disorders;
- History of head trauma or loss of consciousness;
- Substance dependence/abuse other than to cigarettes;
- Presence of acute or chronic illness or history of chronic illness sufficient to invalidate the volunteer's participation in the study or make it unnecessarily hazardous and judge significant by the principal investigator;
- Likelihood that the volunteer will not comply with the requirements of the study or other reason the investigator judges the subject is not suitable;
- Objection by a General Practitioner (GP), or another doctor responsible for their treatment, to the healthy control entering study.
Trial locations and contacts
1 site in 1 country.
Guy Gitlin-Leigh contact
United Kingdom1 site, 1 recruiting
- Recruiting
Institute of Psychiatry, Psychology and Neuroscience
London, SE5 8AB
James Scott, +44 207 848 0002, james.1.scott@kcl.ac.uk
Guy Gitlin-Leigh, guy.1.gitlin-leigh@kcl.ac.uk
About this study
The goal of this basic science study is to to explore the responsivity of glutamate in the brain of treatment-resistant schizophrenia patients to the drug riluzole. The main aims of the study are:
To assess the role of glutamate in treatment-resistant schizophrenia using magnetic resonance spectroscopy.
Read more
To assess the relationship between glutamate levels and brain structural and functional measures (using: structural MRI; functional MRI (fMRI) and arterial spin labelling (ASL)) at baseline.
To assess the relationship between longitudinal change in glutamate levels and brain structural and functional measures.
To assess the relationship between longitudinal change in glutamate levels and changes in psychopathology.
The researchers will compare the changes with healthy controls and those without treatment-resistant schizophrenia.
- Being tested
- Riluzole
- Keywords
- schizophrenia, treatment-resistant schizophrenia, glutamate, riluzole
- Medical subject headings
- Schizophrenia, Treatment-Resistant, Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RiluzoleDrug
50mg twice daily (100mg total daily) for 56 days.
| Study group | Role | What they receive |
|---|---|---|
| Treatment-resistant schizophrenia patients receiving riluzole | Experimental | Not described Receives: Drug: Riluzole |
| Treatment-responsive schizophrenia patients | No intervention | Not described |
| Healthy controls | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in glutamate levels (using magnetic resonance spectroscopy) pre- and post-riluzole administration
Change in glutamate levels will be assessed (using magnetic resonance spectroscopy) in treatment-resistant schizophrenia patients compared with controls and patients without treatment-resistant schizophrenia
Measured: Brain measurements will be conducted at baseline (day -7 to day -1 before riluzole administration), day 7 and day 56 (+- 14 days)
Secondary outcomes (3)
Correlation of glutamate (using magnetic resonance spectroscopy) with brain functional measures at baseline (using functional magnetic resonance imaging)
Measured: Brain measurements will be conducted at baseline (day -7 to day -1 before riluzole administration), day 7 and day 56 (+- 14 days)
Longitudinal change in glutamate levels (using magnetic resonance spectroscopy) correlated with longitudinal change in brain functional measures (using functional magnetic resonance imaging)
Measured: Brain measurements will be conducted at baseline (day -7 to day -1 before riluzole administration), day 7 and day 56 (+- 14 days)
Longitudinal change in glutamate levels (using magnetic resonance spectroscopy) correlated with changes in psychopathology
Changes in psychopathology assessed using rating scales Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression scale (CGI), Calgary Depression Scale for Schizophrenia (CDSS), Montgomery and Asberg Depression Rating Scale (MADRS), Hopkins Verbal Learning Test (HVLT) and a computerised cognitive task
Measured: Brain measurements will be conducted at baseline (day -7 to day -1 before riluzole administration), day 7 and day 56 (+- 14 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2024
- Study start14 Nov 2022
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment-resistant 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- This is a basic science study the purpose of which is to to explore the responsivity of glutamate in treatment-resistant schizophrenia to a given challenge (riluzole).
- Masking
- None (open label)
- Enrolment
- 288 participants (estimated)
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
- NCT06270108
- Sponsor's protocol ID
- 22/SS/0040
- Other IDs
- 299382
- Acronym
- RESTORE
- Status last verified
- Mar 2024
- First submitted
- 29 Jan 2024
- Last updated
- 5 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Glutamatergic Function in the Pathophysiology of Treatment-resistant Schizophrenia
- ClinicalTrials.gov ID
- NCT06270108
- Acronym / sponsor ID
- RESTORE / 22/SS/0040
- Keywords
- schizophrenia, treatment-resistant schizophrenia, glutamate, riluzole
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 288 participants (estimated)
- Lead sponsor
- King's College LondonUniversity, hospital or other
- Collaborators
- South London and Maudsley NHS Foundation Trust
- Study start
- 14 Nov 2022 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 21 Feb 2024 (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.
The goal of this basic science study is to to explore the responsivity of glutamate in the brain of treatment-resistant schizophrenia patients to the drug riluzole. The main aims of the study are:
To assess the role of glutamate in treatment-resistant schizophrenia using magnetic resonance spectroscopy.
To assess the relationship between glutamate levels and brain structural and functional measures (using: structural MRI; functional MRI (fMRI) and arterial spin labelling (ASL)) at baseline.
To assess the relationship between longitudinal change in glutamate levels and brain structural and functional measures.
To assess the relationship between longitudinal change in glutamate levels and changes in psychopathology.
The researchers will compare the changes with healthy controls and those without treatment-resistant schizophrenia.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- This is a basic science study the purpose of which is to to explore the responsivity of glutamate in treatment-resistant schizophrenia to a given challenge (riluzole).
| Arm | Type | Receives |
|---|---|---|
| Treatment-resistant schizophrenia patients receiving riluzole | Experimental | Drug: Riluzole |
| Treatment-responsive schizophrenia patients | No intervention | – |
| Healthy controls | No intervention | – |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Aged 18 years old or older;
- No diagnosis of schizophrenia, schizophreniform or any psychotic disorder;
- Sufficient understanding of the nature of the study and any hazards of participating in it;
- Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of the entire study;
- Willingness to give written consent to participate after reading the information and consent form, and after having the opportunity to discuss the study with the investigator or his delegate;
Key exclusion criteria (7 listed)
- Co-morbid psychiatric or other CNS disorder;
- Family history of Schizophrenia or Psychotic disorders;
- History of head trauma or loss of consciousness;
- Substance dependence/abuse other than to cigarettes;
- Presence of acute or chronic illness or history of chronic illness sufficient to invalidate the volunteer's participation in the study or make it unnecessarily hazardous and judge significant by the principal investigator;
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 |
|---|---|---|
| Riluzole50mg twice daily (100mg total daily) for 56 days. | Drug | Treatment-resistant schizophrenia patients receiving riluzole |
Primary outcome
Change in glutamate levels (using magnetic resonance spectroscopy) pre- and post-riluzole administration
Time frame: Brain measurements will be conducted at baseline (day -7 to day -1 before riluzole administration), day 7 and day 56 (+- 14 days)
Change in glutamate levels will be assessed (using magnetic resonance spectroscopy) in treatment-resistant schizophrenia patients compared with controls and patients without treatment-resistant schizophrenia
3 secondary outcomes
Correlation of glutamate (using magnetic resonance spectroscopy) with brain functional measures at baseline (using functional magnetic resonance imaging)
Time frame: Brain measurements will be conducted at baseline (day -7 to day -1 before riluzole administration), day 7 and day 56 (+- 14 days)
Longitudinal change in glutamate levels (using magnetic resonance spectroscopy) correlated with longitudinal change in brain functional measures (using functional magnetic resonance imaging)
Time frame: Brain measurements will be conducted at baseline (day -7 to day -1 before riluzole administration), day 7 and day 56 (+- 14 days)
Longitudinal change in glutamate levels (using magnetic resonance spectroscopy) correlated with changes in psychopathology
Time frame: Brain measurements will be conducted at baseline (day -7 to day -1 before riluzole administration), day 7 and day 56 (+- 14 days)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2024.
- 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.
Guy Gitlin-Leigh contact
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 Early Phase 1 study testing Riluzole in people with Treatment-resistant Schizophrenia and Treatment-responsive 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 6 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: status not confirmed, as of the sponsor's last update on 5 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. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact James Scott (+44 207 848 0002, james.1.scott@kcl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in glutamate levels (using magnetic resonance spectroscopy) pre- and post-riluzole administration (time frame: Brain measurements will be conducted at baseline (day -7 to day -1 before riluzole administration), day 7 and day 56 (+- 14 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Mar 2024.