Dual Modulation of Sigma-1 and NMDA Receptors in the Treatment of Schizophrenia

Phase

Condition

Schizotypal Personality Disorder (Spd)

Post-traumatic Stress Disorders

Psychosis

Treatment

S1RA plus Placebo Cap

S1RA plus NMDAE

Clinical Study ID

NCT06574360

CMUH112-REC3-202

Ages 18-65
All Genders

Study Summary

sigma-1 receptor (S1R) agonistic property have been tested in clinical trials for the treatment of schizophrenia. In addition, previous studies found that some NMDA receptor (NMDAR)-enhancing agents were able to improve clinical symptoms of patients with chronic schizophrenia. Whether combined treatment of an S1R agonist and an NMDA-enhancing agent can be better than an S1R agonist alone deserves study.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Have a DSM-5 (American Psychiatric Association) diagnosis of schizophrenia
Are resistant to adequate treatments of at least two antipsychotics (excludingclozapine)
Remain symptomatic but without clinically significant fluctuation, while theirantipsychotic doses are unchanged for at least 3 months and will be maintainedduring the period of the 8-week trial
PANSS total score >70
Hamilton Depression Rating Scale-17 items (HAMD) <7
Are physically healthy and laboratory assessments (including blood routine,biochemical tests) are clinically insignificant.
Have sufficient education to communicate effectively and are capable of completingthe assessments of the study.
Agree to participate in the study and provide informed consent

Exclusion

Exclusion Criteria:

DSM-5 diagnosis of intellectual disability or substance (including alcohol) usedisorder
History of epilepsy, head trauma, central nervous system diseases or mentaldisorders other than schizophrenia (including major depressive disorder, bipolardisorders, persistent depressive disorder, obsessive-compulsive disorder)
Pregnancy or lactation
Inability to follow protocol

Study Design

S1RA plus Placebo Cap

September 23, 2024

March 31, 2029

Study Description

The current treatment for schizophrenia remains unsatisfactory; thus, development of new treatments is vital. Both sigma-1 receptor (S1R) dysfunction and NMDA receptor (NMDAR) hypofunction contribute to pathogenesis of schizophrenia, especially treatment-resistant schizophrenia. Several S1R agonists have been tested for its potential for schizophrenia treatment; however, its efficacy appears limited. In addition, previous studies also found that some NMDA-enhancing agents were able to augment efficacy of antipsychotics in the treatment of chronic schizophrenia. Whether combined treatment of an S1R agonist and an NMDA-enhancer (NMDAE) can be better than an S1R agonist alone deserves study. Therefore, this study aims to compare an S1R agonist plus an NMDAE and an S1R agonist plus placebo in the treatment of treatment-resistant schizophrenia. The subjects are the patients with treatment-resistant schizophrenia who have responded poorly to two or more kinds of antipsychotics treatment. They keep their original treatment and are randomly, double-blindly assigned into two treatment groups for 12 weeks: (1) S1R agonist (S1RA) plus NMDAE, or (2) S1RA plus placebo. Clinical performances and side effects are measured at weeks 0, 2, 4, 6, and 8. Cognitive functions are assessed at baseline and at endpoint of treatment by a battery of tests. The efficacies of S1RA plus NMDAE and S1RA 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). All p values for clinical measures will be based on two-tailed tests with a significance level of 0.05.

Connect with a study center

Department of Psychiatry, China Medical University Hospital
Taichung,
Taiwan
Active - Recruiting

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