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

NCT ID: NCT05240976

Last Updated: 2024-08-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-02-23

Study Completion Date

2027-03-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Schizophrenia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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NMDAE plus Anti-inflammatory Agent (AIFA)

An NMDA enhancer plus a drug with anti-inflammatory property

Group Type EXPERIMENTAL

NMDAE plus AIFA

Intervention Type DRUG

Use of an NMDA enhancer plus a drug with anti-inflammatory property for the treatment of ultra-resistant schizophrenia.

NMDAE plus Placebo

An NMDA enhancer plus Placebo

Group Type PLACEBO_COMPARATOR

NMDAE plus Placebo Cap

Intervention Type DRUG

Use of an NMDA enhancer plus placebo as a comparator

Interventions

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NMDAE plus AIFA

Use of an NMDA enhancer plus a drug with anti-inflammatory property for the treatment of ultra-resistant schizophrenia.

Intervention Type DRUG

NMDAE plus Placebo Cap

Use of an NMDA enhancer plus placebo as a comparator

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Health Research Institutes, Taiwan

OTHER

Sponsor Role collaborator

China Medical University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Department of Psychiatry, China Medical University Hospital

Taichung, , Taiwan

Site Status RECRUITING

Countries

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Taiwan

Central Contacts

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

Role: CONTACT

886 4 22052121 ext. 1855

Facility Contacts

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

Role: primary

886 4 22052121 ext. 1855

Other Identifiers

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CMUH109-REC3-043

Identifier Type: -

Identifier Source: org_study_id

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