Combination of NMDA-enhancing and Anti-inflammatory Treatments for Ultra-resistant Schizophrenia

China Medical University

Status and phase: Enrolling; Phase 2

Conditions: Schizophrenia

Treatments: Drug: NMDAE plus Placebo Cap; Drug: NMDAE plus AIFA

Study type: Interventional

Funder types: Other

Identifiers

NCT05240976

CMUH109-REC3-043

Details and patient eligibility

About

Previous study found that some NMDA-enhancing agent was able to augment efficacy of clozapine for clinical symptoms but not cognitive function in the treatment of ultra-resistant schizophrenia. In addition, several drugs with anti-inflammatory properties have been tested in clinical trials for the treatment of schizophrenia. Whether a drug with anti-inflammatory property can strengthen the efficacy of an NMDA-enhancer (NMDAE) in the treatment of ultra-resistant schizophrenia remains unknown.

Full description

Several lines of evidence suggest that both NMDA and inflammatory hypotheses have been implicated in schizophrenia. Previous study found that some NMDA-enhancing agent was able to augment efficacy of clozapine for clinical symptoms but not cognitive function in the treatment of ultra-resistant schizophrenia. In addition, several drugs with anti-inflammatory properties have been tested in clinical trials for the treatment of schizophrenia. Whether a drug with anti-inflammatory property can strengthen the efficacy of an NMDA-enhancer (NMDAE) in the treatment of ultra-resistant schizophrenia remains unknown.

Therefore, this study aims to compare NMDAE plus a drug with anti-inflammatory property and NMDAE plus placebo in the treatment of ultra-resistant schizophrenia. The subjects are the patients with ultra-resistant schizophrenia who have responded poorly to clozapine treatment. They keep their original clozapine treatment and are randomly, double-blindly assigned into two treatment groups for 12 weeks: (1) NMDAE plus Anti-inflammatory Agent (AIFA), or (2) NMDAE plus placebo. Cognitive functions are assessed at baseline and at endpoint of treatment by a battery of tests. Clinical performances and side effects are measured at weeks 0, 2, 4, 6, 9, and 12. The efficacies of NMDAE plus AIFA and NMDAE plus placebo will be compared.

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) for both primary and secondary outcomes . All p values for clinical measures will be based on two-tailed tests with a significance level of 0.05.

Enrollment: 80 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Have a DSM-5 (American Psychiatric Association) diagnosis of schizophrenia
• Are treatment-resistant to standard treatments of at least two specific antipsychotics before clozapine treatment
• Are receiving adequate trials of clozapine for more than 12 weeks but without satisfactory response
• PANSS total score ≥ 70; SANS total score ≥ 40
• Have sufficient education to communicate effectively and are capable of completing the assessments of the study
• Agree to participate in the study and provide 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 significant laboratory screening tests (including blood routine, biochemical tests)
• Pregnancy or lactation
• Inability to follow protocol

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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80 participants in 2 patient groups, including a placebo group

NMDAE plus Anti-inflammatory Agent (AIFA)

Experimental group

Description:

An NMDA enhancer plus a drug with anti-inflammatory property

Treatment:

Drug: NMDAE plus AIFA

NMDAE plus Placebo

Placebo Comparator group

Description:

An NMDA enhancer plus Placebo

Treatment:

Drug: NMDAE plus Placebo Cap