Dual Modulation of Sigma-1 and NMDA Receptors in the Treatment of Schizophrenia
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: S1RA plus NMDAE, S1RA plus Placebo Cap.
- Who it may be relevant to
- Registry conditions: Schizophrenia. Basic parameters: 18 years — 65 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Taiwan
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
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.
Detailed 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.
Interventions
- Drug S1RA plus NMDAE
Use of an S1R agonist plus an NMDA enhancer for the treatment of treatment-resistant schizophrenia. - Drug S1RA plus Placebo Cap
Use of an S1R agonist plus placebo as a comparator
Primary outcome measures
- Change of Positive and Negative Syndrome Scale (PANSS) [Time frame: week 0, 2, 4, 6, 8]
Secondary outcome measures (6)
- Change of scales for the Assessment of Negative Symptoms (SANS) total score [Time frame: week 0, 2, 4, 6, 8]
- Positive subscale, Negative subscales, and General Psychopathology subscale of PANSS [Time frame: week 0, 2, 4, 6, 8]
- Clinical Global Impression [Time frame: week 0, 2, 4, 6, 8]
- Global Assessment of Functioning [Time frame: week 0, 2, 4, 6, 8]
- Quality of Life Scale [Time frame: week 0, 2, 4, 6, 8]
- Cognitive function [Time frame: Week 0, 8]
Eligibility criteria
Inclusion criteria
- Have a DSM-5 (American Psychiatric Association) diagnosis of schizophrenia
- Are resistant to adequate treatments of at least two antipsychotics (excluding clozapine)
- Remain symptomatic but without clinically significant fluctuation, while their antipsychotic doses are unchanged for at least 3 months and will be maintained during 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 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, central nervous system diseases or mental disorders other than schizophrenia (including major depressive disorder, bipolar disorders, persistent depressive disorder, obsessive-compulsive disorder)
- Pregnancy or lactation
- Inability to follow protocol
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Triple blind
- Primary purpose
- Treatment
Study locations
Taiwan · 1 center
- Department of Psychiatry, China Medical University Hospital — Taichung
Identifiers
NCT: NCT06574360 · CMUH112-REC3-202