Psychosis Mental and Behavioural Disorders
Conditions
Interventions
The study includes two parts:
1. Intervention part: Approximately 60 participants with psychosis (intervention cohort) who have evidence of low-grade inflammation (i.e., IL-6 =0.7pg/ml) and inflammati
Sponsors
University of Bristol
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria for All Participants 1. Able and willing to give informed consent, including consent to share information with the participant’s General Practitioner (GP) and to access secondary care and GP records. 2. Able to understand written and spoken English. 3. Willing to consent to blood sampling. 4. Willing to abstain from strenuous exercise for 72 hours before the assessment visits. 5. Age: 18 - 40 years (inclusive) at the time of eligibility assessment. Additional Inclusion Criteria for Neuroimaging 6. Able and willing to consent to MRI scanning. Additional Inclusion Criteria for Healthy Controls 7. No current or lifetime psychiatric diagnosis. Additional Inclusion Criteria for All Individuals with Psychosis 8. Diagnosis of psychosis: meet ICD-10 criteria for a diagnosis of schizophrenia and related psychoses (ICD-10 code F20, F22, F25, F28, F29) at the time of eligibility assessment and within three years of first diagnosis of psychotic disorder. 9. On stable treatment regime with no recent (within 2 weeks) initiation, cessation, or change in class of antipsychotic medication. 10. No indication of other reason for preclusion into research (e.g., risk to others) as determined by their clinical team. 11. Positive and Negative Syndrome Scale (PANSS) item score >=3 on P1 (delusions), P2 (conceptual disorganisation), P3 (hallucinatory behaviour), OR P6 (suspiciousness/persecution). Additional Inclusion Criteria for Intervention Group 12. Evidence of immune activation: required at eligibility and at baseline visit to enter the study. Serum IL-6 level >=0.7pg/ml will be used as a measure of immune activation. 13. Inflammation-related symptom: Temporal Experience of Pleasure Scale (TEPS) anticipatory pleasure score <=41 (based upon item numbers 1, 3, 7, 11, 12, 14, 15, 16, 17, and 8) and consummatory pleasure score <=36 (based upon item numbers 2, 4, 5, 6, 8, 9, 10, and 13). 14. COVID-19 immunity: evidence of COVID-19 immunity required prior to infusion. Immunity will be confirmed before randomisation using evidence of vaccination and antibody titre test. Additional Inclusion Criteria for Patients with Psychosis and No Inflammation 15. No evidence of immune activation: required at eligibility and at baseline visit to enter the study. Serum/plasma IL-6 level <0.7pg/ml will be used to confirm no evidence of immune activation.
Exclusion criteria
Exclusion criteria: Exclusion Criteria for All Participants 1. Pregnancy (confirmed by urine pregnancy test) or breast feeding. 2. Body mass index (BMI) >35 kg/m² (i.e., WHO obesity class II or above). 3. Current or lifetime diagnosis of antisocial personality disorder, autism or other neurodevelopmental disorder, major traumatic brain injury (determined by Chief Investigator). 4. Currently active diagnosed eating disorder likely to compromise ability to take part (determined by Chief Investigator). 5. History of alcohol or substance use disorder (abuse/dependence) within six months prior to eligibility assessment (nicotine and caffeine dependence are not exclusionary). 6. Current use of medication likely to compromise interpretation of immunological data (including, but not limited to, antibiotics, regular non-steroidal anti-inflammatory drugs, oral/injectable corticosteroids – or any other substances to be determined by the Chief Investigator). 7. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other opportunistic infections. 8. Current or past infection including tests for TB, Hepatitis B, Hepatitis C, VZV or HIV confirmed by blood test. Chest X-ray will be also done to exclude TB. 9. Any major episode of infection requiring hospitalisation or treatment with IV antibiotics within 4 weeks of eligibility assessment. 10. Unstable cardiac, pulmonary, renal, hepatic, endocrine, hematologic, or active infectious disease, including current or prior malignancy. 11. Diverticulitis, inflammatory bowel disease, or uncontrolled gastric/duodenal ulcer. 12. Rheumatic autoimmune disease, mixed connective tissue disease, scleroderma, polymyositis, or significant systemic involvement secondary to rheumatoid arthritis. 13. Current and active ischemic heart disease, e.g., unstable angina. 14. Uncontrolled hypertension defined as systolic blood pressure >170 or diastolic blood pressure >110. 15. History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies. 16. No history of chicken pox infection or no history of varicella zoster vaccination. Additional Exclusion Criteria for Neuroimaging 17. Contraindications to MRI scanning.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measure as of 16/01/2023: Anhedonia assessed using the anticipatory and consummatory pleasure scores of the Temporal Experience of Pleasure Scale (TEPS) at approximately day 14 post-infusion _____ Previous primary outcome measure: Anhedonia measured using the Temporal Experience of Pleasure Scale (TEPS) at baseline and after infusion around day 7, 14, and 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 16/01/2023: Clinical outcomes collected at baseline and after infusion around days 7, 14, and 28: 1. Positive and negative symptoms in psychosis measured via the Positive and Negative Syndrome Scale (PANSS) test and Scale for the Assessment of Negative Symptoms (SANS) 2. Depressive symptoms measured via the Calgary Depression Scale for Schizophrenia (CDSS) 3. Fatigue levels measured with the Multi-dimensional Fatigue Inventory (MFI) 4. General quality of life measured by the European Quality of Life-5 Dimensions Three-Level Version (EQ-5D-3L) 5. Subjective wellbeing measured using the Visual Analogue Scale for Subjective Wellbeing (VAS-W) Cognitive outcomes collected at baseline and after infusion around day 14 : 6. Psychomotor speed assessed using CANTAB Reaction Time (RTI) test or a similar test (computerised) and with the Symbol Coding Test (pen and paper) or a similar test 7. Attention measured using CANTAB Rapid Visual Information Processing (RVP) test or a similar test (computerised) 8. Memory assessed with the CANTAB Paired Associates Learning (PAL) test or a similar test (computerised) 9. Executive function will be assessed using the CANTAB One Touch Stockings of Cambridge (OTS) test or a similar test (computerised) at baseline and 14 days post-infusion Neuroimaging outcomes collected at baseline and after infusion around day 14: 10. Brain structure assessed using Whole Brain T1 Weighted Structural MRI performed using 3D volumetric spoiled gradient echo at baseline and 14 days post-infusion 11. Brain function assessed using a 1H-MRS measure of glutathione in the prefrontal cortex with 30x30x30 mm spectroscopic voxel at baseline and 14 days post-infusion 12. Brain oxidative stress levels assessed using a 10-min resting state fMRI scan with blood oxygenation-level-dependent (BOLD) images at baseline and 14 days post-infusion Blood biomarker outcomes collected at baseline and after infusion around days 7, 14, and 28: | — |
Countries
England, United Kingdom
Outcome results
None listed