Sex differences in NMDA-enhancing treatment for schizophrenia

Sex Differences in NMDA-enhancing Treatment of Schizophrenia

This trial will see if an NMDA-enhancer reduces negative symptoms in men and women with schizophrenia who are stable on antipsychotic medication.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 20 Years to 65 Years
• Sex: All
• Sponsor: China Medical University Hospital (other)
• Locations: 1 site (Taichung)
• Trial ID: NCT07122895 on ClinicalTrials.gov

What this trial studies

This randomized, double-blind, placebo-controlled Phase 2 trial enrolls 90 adults with schizophrenia and predominantly negative symptoms. Participants remain on their stable antipsychotic dose and are randomly assigned 2:1 to receive an NMDA-enhancer (N=60) or placebo (N=30) for 12 weeks, with equal numbers of men and women in each arm. Primary outcome is change in the Scale for Assessment of Negative Symptoms (SANS) with assessments at baseline and weeks 4, 8, and 12; secondary outcomes include PANSS-negative, CGI, quality of life, global functioning, cognitive domains, and side effects. Repeated measures will be analyzed using generalized estimating equations and standard tests for between-group comparisons.

Who should consider this trial

Good fit: Adults with DSM-5 schizophrenia who have had predominantly persistent negative symptoms for at least 6 months, meet the study SANS and PANSS-negative thresholds, are physically stable, and have been on a fixed antipsychotic dose for ≥6 months.

Not a fit: Patients with prominent positive symptoms, recent clinical instability, substance use disorders, intellectual disability, clinically significant lab abnormalities, or who cannot attend in-person visits are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, the treatment could lessen negative symptoms and improve daily functioning and quality of life, and clarify whether men and women respond differently.

How similar studies have performed: Previous trials of NMDA-targeting agents for negative symptoms have shown mixed and limited benefits in small studies, so this approach is partially tested but not yet proven.

Eligibility criteria

Inclusion Criteria:

* Have a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of schizophrenia
* keep stable mentally for ≥ 6 months before baseline and meet the following clinical criteria: predominantly negative symptoms for ≥ 6 months, a minimum baseline total score of 40 on the SANS, a minimum baseline score of 24 on the negative subscale of the PANSS, and a maximum score of 3 on each item of PANSS-positive subscale;
* Are physically healthy and laboratory assessments (including blood routine, biochemical tests) are clinically insignificant;
* Have been keeping a fixed dose of antipsychotics for at least 6 months, and that is not allowed to change during the 12-week study period
* Have sufficient education to communicate effectively and are capable of completing the assessments of the study
* Agree to participate in the study and provide written informed consent

Exclusion Criteria:

* DSM-5 diagnosis of intellectual disability or substance (including alcohol) use disorder
* History of epilepsy, head trauma, or serious medical or central nervous system diseases (other than schizophrenia) which may interfere with the study
* Clinically evident depressive symptoms or a baseline score\>7 on the Hamilton Depression Rating Scale-17 items
* Clinically relevant parkinsonism or a baseline score \>3 on the sum of the first eight items of the Simpson-Angus Scale (SAS)
* Pregnancy or lactation
* Inability to follow protocol

Where this trial is running

Taichung

• Department of Psychiatry, China Medical University Hospital — Taichung, Taiwan (RECRUITING)

Study contacts

• Study coordinator: Hsien-Yuan Lane, M.D., Ph.D

Conditions: Schizophrenia, NMDA, Negative symptoms, Sex difference