Energetics and Glutamate in Schizophrenia

Recruiting

• Conditions: Schizophrenia
• Interventions: Procedure: MRI scan; Procedure: PET-MR scan

• Registration Number: NCT06236048
• Lead Sponsor: King's College London

Brief Summary

The goal of this case-control study is to compare brain glutamate, glucose utilisation, lactate production and brain activity in healthy volunteers and people with a diagnosis of schizophrenia.

It investigates the following main questions:

Whether, compared to healthy volunteers, participants with schizophrenia show:

1. reduction in brain glucose utilisation

2. increased brain lactate

3. greater variability in brain glutamate

Participants will be asked to have a screening visit, a MRI brain scan and a PET-MRI brain scan.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-01-24
• Study First Submitted QC: 2024-01-31
• Status Verified: 2024-02
• Study First Posted: 2024-02-01
• Last Update Submitted: 2024-02-22
• Last Update Posted: 2024-02-26
• Study Start: 2024-03-01
• Primary Completion: 2027-12-31
• Study Completion: 2028-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 75

Inclusion Criteria

Healthy volunteer group:

1. No history of psychiatric illness, as assessed on the Mini neuropsychiatric Interview (MINI).

Treatment responsive schizophrenia group:

1. Meeting ICD-11 criteria for schizophrenia (F20)
2. Meeting symptomatic consensus criteria for remission, defined as scores of mild or less on items P1, P2, P3, N1, N4, N6, G5 and G9 of the PANSS and no history of symptomatic relapse in the past 6 months.
3. Currently receiving one or more of the following antipsychotic medications: Olanzapine; Risperidone; Quetiapine; Amisulpride; Aripiprazole; Paliperidone.
4. Antipsychotic adherent, defined as having a score of >=moderate adherence on the Kemp scale.

Treatment-resistant schizophrenia group:

1. Meeting ICD-11 criteria for schizophrenia (F20)
2. Meeting modified consensus criteria for treatment resistance, including history of at least two antipsychotic treatment trials each lasting ≥6 weeks at a dose of ≥400mg chlorpromazine equivalents.
3. Total PANSS total score > 70
4. Moderate functional impairment (<60 on the SOFAS)
5. Currently receiving one or more of the following antipsychotic medications: Clozapine; Olanzapine; Risperidone; Quetiapine; Amisulpride; Aripiprazole; Paliperidone.
6. Antipsychotic adherent, defined as having a score of >=moderate adherence on the Kemp scale.

Exclusion Criteria

All participants:

1. Pregnancy or breastfeeding

2. Lacking in mental capacity to provide informed consent to study participation.

3. Diabetes or history of taking an antidiabetic medication 3. Presence of contraindication to MRI at 7 Tesla, including metallic or electronic implants and dental wires.

4. Severe claustrophobia prohibiting participation on PET or MRI 5. Body size above the comfortable limits for the MRI scanner. 6. Previous participation in research or clinical procedure/s involving ionising radiation, which, including the current study, would result in total radiation exposure >=10mSv within 12 months 7. History of head injury resulting in loss of consciousness for > 5 minutes 8. Meeting ICD-11 criteria for organic mental disorder (F00-F09) 9. Meeting ICD-11 criteria for mental and behavioural disorders due to psychoactive substance use (F10-F19) 10. With exclusion of nicotine or cannabis, meeting ICD-11 criteria for psychoactive substance dependence 11. Participation in clinical trial investigating any pharmacological agent other than a licensed antipsychotic compound in the last month.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Treatment resistant schizophrenia	MRI scan	-
Schizophrenia - remission	MRI scan	-
Treatment resistant schizophrenia	PET-MR scan	-
Healthy volunteers	PET-MR scan	-
Schizophrenia - remission	PET-MR scan	-
Healthy volunteers	MRI scan	-

Primary Outcome Measures

Name	Time	Method
Glutamate - anterior cingulate cortex	1 day	Glutamate and glutamine measured using magnetic resonance spectroscopy at 7 Tesla
Cortical network activity	1 day	Network activity / connectivity as measured using fMRI at 3 Tesla
Brain glucose utilisation	1 day	Measured using fully quantitative 18F-fluorodeoxyglucose PET (CMRglc)
Lactate - visual cortex	1 day	Measured using magnetic resonance spectroscopy at 7 Tesla at rest and during visual stimulation
Cerebral blood flow	1 day	Measured using arterial spin labelling, 3 Tesla MRI

Trial Locations

Locations (1)

South London and the Maudsley NHS Foundation Trust; 🇬🇧 London, United Kingdom