Sex Differences in NMDA-enhancing Treatment of Schizophrenia

NCT ID: NCT07122895

Last Updated: 2025-09-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-16
• Study Completion Date: 2030-03-31

Brief Summary

Schizophrenia differs between sexes in clinical symptoms and functional outcome. Negative symptoms are the core pathology of this disease. NMDA receptor (NMDAR) dysfunction is a key factor in negative symptoms. This study aims to examine the sex difference in the efficacy of an NMDA-enhancer (NMDAE) for the treatment of negative symptoms in schizophrenia.

Detailed Description

Schizophrenia differs between sexes in clinical symptoms and functional outcome. Negative symptoms, the core pathology of this disease, principally determine the patients' prognoses. NMDAR dysfunction is a key factor in negative symptoms. Whether NMDAR-enhancing treatment can improve negative symptoms and whether there is sex difference need to be studied. The subjects are the schizophrenia patients with predominantly negative symptoms. They will continue their original treatment and be double-blindly, randomly assigned to receive 12-week: (1) NMDAE (N = 60), or (2) placebo (N = 30). There will be half men and half women in each group. We will measure clinical manifestations and side effects at weeks 0, 4, 8, and 12 using Scale for Assessment of Negative Symptoms (the primary outcome), Positive and Negative Syndrome Scale-negative subscale, Clinical Global Impression, Quality of Life Scale, Global Assessment of Function, and scale of side effects. At week 0 and week 12, we will assess 7 cognitive domains. Chi-square (or Fisher's exact test) will be used to compare differences of categorical variables and t-test (or Mann-Whitney test if the distribution is not normal) for continuous variables between treatment groups. Mean changes from baseline in repeated-measure assessments will be assessed using the generalized estimating equation (GEE). All p values for clinical measures will be based on two-tailed tests with a significance level of 0.05.

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

NMDAE

An NMDA enhancer

Group Type: EXPERIMENTAL

NMDAE

Intervention Type: DRUG

Use of an NMDA enhancer for the treatment of negative symptoms

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo Cap

Intervention Type: DRUG

Use of placebo as a comparator

Interventions

NMDAE

Use of an NMDA enhancer for the treatment of negative symptoms

Intervention Type: DRUG

Placebo Cap

Use of placebo as a comparator

Intervention Type: DRUG

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Science and Technology Council, Taiwan

OTHER_GOV

Sponsor Role: collaborator

China Medical University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Department of Psychiatry, China Medical University Hospital

Taichung, , Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Hsien-Yuan Lane, M.D., Ph.D

Role: CONTACT

hylane@gmail.com

886 4 22052121 ext. 11855

Facility Contacts

Hsien-Yuan Lane, M.D., Ph.D

Role: primary

hylane@gmail.com

886 4 22052121 ext. 11855

Other Identifiers

CMUH114-REC3-042

Identifier Type: -

Identifier Source: org_study_id