A Study Evaluating the Efficacy of Xanomeline/Trospium (XT) on Cognitive Impairment After 24 and 52 Weeks of Treatment in Adult Participants With Schizophrenia

Starting soon · Phase 3

Conditions studied: Schizophrenia; Psychosis, Cognitive Impairment

In brief

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.

Key facts

Study ID

NCT07084831

Run by

European Group for Research In Schizophrenia

People needed

171

Starts

2027-01-01

Expected to finish

2029-07-01

Last updated by the study team

2026-05-13

Who can join

Age: 18 and older, up to 55. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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 on a stable dose of oral antipsychotic medication(s) for at least 4 weeks prior to Screening. Participants should be on monotherapy oral AP for baseline visit.
• Have a SCIP total below 70.
• Test negative for pregnancy at the screening visit and must be using a highly effective contraceptive method during the study and 30 days after the study, if being a female of childbearing potential.

You may not qualify if…

• 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).
• Have a positive urine toxicology for phencyclidine, amphetamines, opiates (unless participant has a valid prescription for short-term use), cocaine, or alcohol (clinically significant alcohol use in the opinion of the Investigator). Nicotine and caffeine use is allowed. Stimulants and cannabis is allowed when used sporadically and recreationally as per the judgement of the clinician.
• Present with an intellectual disability, drug-induced psychosis, or history of clinically significant brain trauma as per the judgement of the clinician.
• Have current or past use of clozapine (used for at least 6 weeks in an effective dose range) and/or current use of a long-acting injectable antipsychotic, or anticholinergic treatment that cannot be discontinued before the baseline visit.
• Be expected to require more than the allowed psychotropic concomitant medication during the study (from baseline on). This is defined as: needing benzodiazepines of more than 2 mg lorazepam equivalent (daily), quetiapine, antidepressants, mood stabilizers or benzodiazepines at a dose exceeding the allowed threshold. If these treatments are used at the screening visit, they must be tapered down before the baseline visit.
• Have clinically significant abnormal finding on the physical examination, medical history, ECG (at screening), or clinically significant laboratory results at screening.
• Participated in any cognitive remediation/training program or completed the BACS within 4 weeks of Screening.
• Having a known allergy to xanomeline, trospium chloride or any of the ingredients of XT.
• Have current presence of clinically significant cardiovascular, pulmonary, renal, hematologic, gastrointestinal (e.g., obstructive disorders [including conditions that may decrease GI motility, such as ulcerative colitis, intestinal atony, and myasthenia gravis], endocrine, immunologic, dermatologic, neurologic, or oncologic disease or any other condition that, in the opinion of the investigator, would jeopardize the safety of the participant or the validity of the study results. This includes:
• 12a. Have history or high risk of urinary retention. 12b. All grades of hepatic impairment (mild [Child-Pugh Class A], moderate [Child-Pugh Class B], and severe [Child-Pugh Class C]).
• 12c. Elevations in hepatic transaminases at screening ≥ 2× ULN for ALT and AST and/or bilirubin > 2 × ULN, unless in the context of Gilbert's syndrome.
• 12d. Have a history or high risk for narrow-angle glaucoma. 12e. Active biliary disease (e.g., symptomatic gallstones). Participants with other biliary histories are eligible and should be discussed with the sponsor.
• 12f. Participants with a history of bladder stones . 12g. Participants with a history of recurrent urinary tract infections. 12h. For all male participants, serum prostate-specific antigen >10 ng/mL at screening.
• 12i. For male participants ≥ 45 years of age, an IPSS score of 5 (i.e, "almost always") on items 1, 3, 5, or 6, and/or for male participants ≥ 45 years of age, an IPSS score ≥ 9 for the sum of items 1, 3, 5, and 6.
• 12j. An eGFR of < 60 mL/min (which indicates renal dysfunction). 12k. History of unstable hypertension or tachycardia as evidenced by a blood pressure of ≥ 160/100 mmHg at screening and/or a heart rate of ≥ 110 bpm at screening.

Where it is running

• Medical University Innsbruck — Innsbruck, Austria
• UPC KU Leuven — Leuven, Belgium
• National Institute of Mental Health — Klecany, Czechia
• Psykiatrisk Center Glostrup — Glostrup Municipality, Denmark
• University of Augsburg — Augsburg, Germany
• University Hospital Cologne — Cologne, Germany
• Central Institute of Mental Health — Mannheim, Germany
• Ludwig Maximilian University — München, Germany
• Semmelweis University — Budapest, Hungary
• Sheba Medical Center — Ramat Gan, Israel
• University of Campania Luigi Vanvitelli — Naples, Italy
• AOU Città della Salute e della Scienza di Torino — Torino, Italy
• University Medical Center Groningen — Groningen, Netherlands
• Hospital Clínic de Barcelona — Barcelona, Spain
• Hospital Universitario La Paz — Madrid, Spain
• Hospital Universitario Virgen del Rocío — Seville, Spain

Full record on ClinicalTrials.gov

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