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

NCT ID: NCT06574360

Last Updated: 2024-10-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-23
• Study Completion Date: 2029-03-31

Brief 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.

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.

Conditions

Schizophrenia

Study Design

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

Study Groups

S1R agonist (S1RA) plus NMDAE

An S1R agonist plus an NMDA enhancer

Group Type: EXPERIMENTAL

S1RA plus NMDAE

Intervention Type: DRUG

Use of an S1R agonist plus an NMDA enhancer for the treatment of treatment-resistant schizophrenia.

S1R agonist (S1RA) plus placebo

An S1R agonist plus placebo

Group Type: PLACEBO_COMPARATOR

S1RA plus Placebo Cap

Intervention Type: DRUG

Use of an S1R agonist plus placebo as a comparator

Interventions

S1RA plus NMDAE

Use of an S1R agonist plus an NMDA enhancer for the treatment of treatment-resistant schizophrenia.

Intervention Type: DRUG

S1RA plus Placebo Cap

Use of an S1R agonist plus placebo as a comparator

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

Facility Contacts

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

Role: primary

hylane@gmail.com

886 4 22052121 ext. 1855

Other Identifiers

CMUH112-REC3-202

Identifier Type: -

Identifier Source: org_study_id