Schizophrenia, schizoaffective disorder, or schizophreniform disorder Mental and Behavioural Disorders
Conditions
Interventions
Early psychosis participants are randomised in a 1:1 ratio in this Phase III trial to receive either xanomeline–trospium or a dopamine D2 antagonist (risperidone or lurasidone). Randomisation is strat
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Inclusion criteria
Inclusion criteria: General inclusion criteria: 1. Individuals aged 18 to 55 years, willing and able to provide written informed consent 2. In the Investigator’s opinion, is able and willing to comply with all trial requirements 3. Able to understand and communicate in English 4. Body mass index =18 and =40 kg/m2 Additional inclusion criteria for early psychosis participants: 1. The participant meets DSM-5 criteria for schizophrenia, schizoaffective disorder, or schizophreniform disorder, as confirmed through the Mini International Neuropsychiatric Interview (MINI). 2. The participant has previously been treated with an antipsychotic. 3. The participant is within 10 years of first experiencing psychosis. 4. The participant is wishing to either commence an antipsychotic (if not currently receiving treatment), or switch from their current antipsychotic treatment and this is clinically indicated. 5. Attitude to antipsychotic medication is rated 4 or more on the Kemp Clinician Rating Scale (CRS). 6. Participants of childbearing potential (*) and male participants (assigned sex at birth) whose partner is of childbearing potential must confirm that they are using effective contraception, or that their partner is using effective contraception throughout the trial, in accordance with the requirements outlined in the protocol**. 7. The participant is willing to allow their General Practitioner and consultant, if appropriate, to be notified of participation in the trial. Additional inclusion criteria for control participants: 1. No diagnosis of psychiatric disorder other than previous episode(s) of depression or anxiety. 2. The participant is willing and able to undergo MRI/MEG scans. *A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. ** Methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods. Such methods include: 1) combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral; intravaginal; transdermal); 2) progestogen-only hormonal contraception associated with inhibition of ovulation (oral; injectable; implantable); 3) intrauterine device (IUD); 4) intrauterine hormone-releasing system (IUS); 5) bilateral tubal occlusion; 6) vasectomised partner; 7) sexual abstinence (abstinence should only be used as a contraceptive method if it is in line with the subjects’ usual and preferred lifestyle. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not an acceptable method of contraception). The participant agrees to use an acceptable method of contraception for the full duration of the trial and for 30 days after any trial drug administration, unless surgically sterile or postmenopausal.
Exclusion criteria
Exclusion criteria: General exclusion criteria: 1. Pregnancy or breastfeeding. 2. The participant has a current diagnosis of ‘Substance or medication induced psychotic disorder’ or ‘Psychotic disorder due to another medical condition’ as determined through the MINI. 3. Current active suicidal ideation within the last 2 weeks, defined as a score of 1 or higher on CDSS question 8, followed by an assessment by the treating clinician who determines it is not safe for the patient to participate in the trial* 4. Meeting DSM-V criteria for substance use disorder, except for nicotine (mild, moderate, and severe allowed) well as alcohol or cannabis abuse (mild allowed). 5. Positive urine drug screen, except for cannabis provided that cannabis abuse (moderate or severe) or dependency has been ruled out, as determined through the MINI. 6. Participant has participated in another clinical trial in which the participant received an experimental or investigational drug or agent within 2 months before Visit 1. Participants who have participated in Type A studies (e.g. trials of standard and within-label treatments including antipsychotic medication) or non-CTIMP studies (e.g. studies of exercise therapy) must have completed the intervention but may be included if permitted by the protocol of the other trial. 7. The participant refuses any mandatory safety checks during the trial, specifically, refusal of: assessment of suicidality, pregnancy test (early psychosis participants of child-bearing potential only); safety blood test (early psychosis participants only); reporting of Adverse Events (AEs) (early psychosis participants only). 8. Any other significant factor which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial. Additional exclusion criteria for early psychosis participants: 1. The participant meets modified Andreasen criteria for symptomatic remission AND displays no cognitive deficits at the screening visit. 2. Known hepatic impairment (mild, moderate or severe) and/or transaminase elevations levels exceeding the upper limit of normal 3 times or more and bilirubin greater than 2 times the upper limit of normal. 3. Abnormal ECG results at screening (QTC =450 ms for males and =460 ms for females) 4. In addition to abnormal transaminase levels and eGRF levels any other lab values that, based on the investigator’s assessment, may deem the participant unsuitable for inclusion. 5. Known renal dysfunction and/or estimated glomerular filtration rate (eGRF) level below 60 ml/min/1.73 m2. 6. History or high risk of urinary retention, angioedema, gastric retention, or narrow-angle glaucoma. 7. History of serious constipation requiring treatment in the last 6 months 8. History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or oncologic disease or any other condition that, in the opinion of the investigator, would jeopardise the safety of the subject or the validity of the study results. 9. Experienced any adverse effects related to trospium chloride previously, or allergy to any component of trospium chloride tablets 10. Contraindication to treatment with lurasidone AND risperidone. If the participant has a contraindication to just one of these medications, they can still participate in
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cognitive performance measured using the CANTAB composite score from baseline (Visit 2) to 6 weeks post-baseline (Visit 4) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Psychosis symptom severity measured using the Positive and Negative Syndrome Scale (PANSS) total and subscale scores from baseline (Visit 2) to 3- and 6-weeks post-baseline (Visit 3 and Visit 4) 2. Functional capacity measured using the Virtual Reality Functional Capacity Assessment Tool (VRFCAT) from baseline to week 6 3. Individual cognitive domains of the CANTAB measured using individual CANTAB tests from baseline to 6 weeks post-baseline 4. Global clinical severity measured using the Clinical Global Impression – Severity/Improvement scale (CGI-S/I) from baseline to 3- and 6-weeks post-baseline 5. Patient-rated global severity measured using the Patient Global Impression – Severity/Improvement scale (PGI-S/I) from baseline to 3- and 6-weeks post-baseline (Visit 3), and 6 weeks post-baseline (Visit 4) 6. Negative symptom severity measured using the Brief Negative Symptom Scale (BNSS), from baseline, to 3- and 6-weeks post-baseline 7. Subjective cognitive functioning measured using the Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS), from baseline (Visit 2) to 3- and 6-weeks post-baseline 8. Depression symptoms measured using the Calgary Depression Scale for Schizophrenia (CDSS) from baseline to 3- and 6-weeks post-baseline 9. Subjective well-being measured using the Subjective Well-being under Neuroleptics (SWN) scale from baseline (Visit 2) to 3- and 6-weeks post-baseline 10. Work and social adjustment measured using the Work and Social Adjustment Scale (WSAS), from baseline (Visit 2) to 3- and 6-weeks post-baseline 11. Daily functioning measured using the Specific Level of Functioning Scale (SLOF) and the Social and Occupational Functioning Assessment Scale (SOFAS) from baseline (Visit 2) to 6 weeks post-baseline (Visit 4) 12. Quality of life measured using the Recovering Quality of Life scale (ReQoL), from baseline (Visit 2) to 6 weeks post-baseline (Visit 4) 13. Treatment acceptability assessed using the Theoretical Framework of Accepta | — |
Countries
England, United Kingdom
Contacts
Public ContactMichael Sinden
Outcome results
None listed