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.
This is a phase III, prospective, open-label, single-arm, international, multicenter study. At visit 1, the informed consent is signed and screening is performed to confirm eligibility. At visit 2, baseline measures are performed, and the new treatment is initiated. Max. 14 days after the baseline visit, the pre-study antipsychotic treatment is withdrawn via tapering. At visit 3, 4, 5, 7 and 9 participants' general wellbeing and safety is assessed. At visit 6, 8 and 10, baseline measures are repeated. Between visit 6-7, visit 7-8, visit 8-9 and visit 9-10, a phone call is planned to assess general psychopathology, adverse events and concomitant medication. The treatment duration is one year for each participant; with a safety follow up 4 weeks after the end of the trial. All participants are treated with XT open label.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
171
Participants will receive oral xanomeline/trospium during the trial (target dose 125/30 BID).
Medical University Innsbruck
Innsbruck, Austria
NOT_YET_RECRUITINGUPC KU Leuven
Leuven, Belgium
NOT_YET_RECRUITINGNational Institute of Mental Health
Klecany, Czechia
NOT_YET_RECRUITINGPsykiatrisk Center Glostrup
Glostrup Municipality, Denmark
NOT_YET_RECRUITINGUniversity of Augsburg
Augsburg, Germany
NOT_YET_RECRUITINGUniversity Hospital Cologne
Cologne, Germany
NOT_YET_RECRUITINGCentral Institute of Mental Health
Mannheim, Germany
NOT_YET_RECRUITINGLudwig Maximilian University
München, Germany
NOT_YET_RECRUITINGSemmelweis University
Budapest, Hungary
NOT_YET_RECRUITINGSheba Medical Center
Ramat Gan, Israel
RECRUITING...and 6 more locations
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).
Time frame: 24 weeks
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.
Time frame: 24 weeks
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