Schizophrenia is a long-lasting and serious mental health disorder that affects about 1% of people worldwide. It can cause symptoms such as hallucinations and delusions (called positive symptoms), confused or disorganized thinking, reduced motivation and emotional expression (negative symptoms), difficulties with memory and concentration (cognitive symptoms), and movement problems like restlessness or slowed activity. Current treatments, called antipsychotics, mainly work by blocking dopamine in the brain. These medicines are helpful for hallucinations and delusions, but they do little to improve negative or cognitive symptoms.
A new medicine, Xanomeline/Trospium (XT), works differently. It targets a brain system called the muscarinic acetylcholine receptors while limiting side effects elsewhere in the body. Clinical trials have shown that XT reduces psychotic symptoms effectively and is generally well tolerated. The FDA approved XT in 2024 for adults with schizophrenia. Importantly, early results also suggest that XT may help improve thinking and memory (cognition domains), though this has not yet been studied in depth.
Most schizophrenia drug studies pay little attention to long-term changes in cognition, often using only short screening tests. This study will be the first to take a deep look at cognitive function over a full year of XT treatment. It will also examine how changes in thinking skills connect with other aspects of life, such as symptom control, daily functioning, and quality of life. By making cognition a central outcome, the study responds to an urgent need in schizophrenia research: moving beyond just controlling hallucinations and delusions toward improving real-world recovery. The results could help shape future treatment strategies and support the idea that cognition should be a core treatment target in schizophrenia.
Be between 18 and 55 years of age.
Be willing and able to provide informed consent, after the nature of the study has been fully explained. This includes being able to understand the locally approved informed consent (and information letter) in the local language.
Have a current DSM-5 diagnosis of schizophrenia, which needs to be confirmed by MINI.
Have all PANSS positive items + G8 and G10 ≤4 at screening.
Be pregnant, lactating, or less than 3 months postpartum.
Be at significant risk of committing suicide. This is defined as: participants with active suicidal ideation with some intent to act, without specific plan ("Yes" to question 4 of the Columbia-Suicide Severity Rating Scale (C-SSRS) or active suicidal ideation with specific plan and intent ("Yes" to question 5 of the C-SSRS), followed by an assessment by the treating clinician who determines it is not safe for the participant to participate in the study.
Currently meet DSM-5 criteria for a manic episode or major depressive disorder as confirmed by the MINI.
Currently meeting DSM-5 criteria for severe substance and/or alcohol use disorder as confirmed by the MINI (≥6 on module K for alcohol use disorder and/or ≥6 on module J for substance use disorder, unless being in early or sustained remission).
Single group
Xanomeline/trospium
DrugParticipants will receive oral xanomeline/trospium during the trial (target dose 125/30 BID).
Change in cognitive performance after 24 weeks of treatment, relative to baseline.
The within-participant change in the Brief Assessment of Cognition in Schizophrenia composite cognitive score from baseline to follow-up after 24 weeks. Higher score means better cognition. There is no max score, as the tests have different scoring methods (number correct, reaction time).
Change in negative symptoms after 24 weeks of treatment, relative to baseline.
The within-participant change in the Positive And Negative Syndrome Scale (PANSS) negative subscale from baseline to follow-up after 24 weeks. A higher score means more schizophrenia-related symptoms. The maximum score is 49.
Change in Functional Skills assessment and training (FUNSAT) scores for ATM banking, ticket kiosk, and medication management after 12, 24 and 52 weeks of treatment, relative to baseline.
The within-participant change in the Functional Skills assessment and training (FUNSAT) scores for ATM banking, ticket kiosk and medication management from baseline to follow-up after 12, 24 and 52 weeks. Higher reaction time scores means worse functioning (without maximum), higher number correct means better functioning
Change in Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS) between baseline and week 24
The within-participant change in Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS) between baseline and week 24. A higher score means better subjective and social cognition.
Change in Subjective Scale to Investigate Social Cognition Scale scores (MRMET) between baseline and week 24
The within-participant change in Social Cognition Scale scores (MRMET) between baseline and week 24. A higher score means better subjective and social cognition.
Change in Brief Assessment of Cognition in Schizophrenia (BACS) scores between baseline to week 12 and week 52.
The within-participant change in Brief Assessment of Cognition in Schizophrenia (BACS) scores between baseline to week 12 and week 52. Higher score means better cognition.There is no max score, as the tests have different scoring methods (number correct, reaction time).
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European Group for Research In Schizophrenia
Lead sponsor
Bristol-Myers Squibb
Collaborator
University Medical Center Groningen
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
