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

Previous studies found that some NMDA-enhancing agents were able to improve clinical symptoms of patients with chronic schizophrenia. In addition, several drugs with anti-inflammatory properties have been tested in clinical trials for the treatment of schizophrenia too. Whether combined treatment of an NMDA-enhancing agent and a drug with anti-inflammatory property can be better than an NMDA-enhancing agent alone deserves study.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: NMDAE plus Placebo Cap; Drug: NMDAE plus AIFA

Detailed Description

Several lines of evidence suggest that both NMDA and inflammatory hypotheses have been implicated in schizophrenia. Previous studies found that some NMDA-enhancing agents were able to augment efficacy of antipsychotics in the treatment of chronic schizophrenia. In addition, several drugs with anti-inflammatory properties have been tested in clinical trials for the treatment of schizophrenia too. Whether a drug with anti-inflammatory property can strengthen the efficacy of an NMDA-enhancer (NMDAE) in the treatment of schizophrenia remains unknow. Therefore, this study aims to compare NMDAE plus a drug with anti-inflammatory property and NMDAE plus placebo in the treatment of 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) NMDAE plus Anti-inflammatory Agent (AIFA), or (2) NMDAE plus placebo. Clinical performances and side effects are measured at weeks 0, 2, 4, 6, 9, and 12. Cognitive functions are assessed at baseline and at endpoint of treatment by a battery of tests. 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). All p values for clinical measures will be based on two-tailed tests with a significance level of 0.05.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hsien-Yuan Lane, M.D., Ph.D; Phone Number: 1855 886 4 22052121; Email: hylane@gmail.com

Study Locations

• Taiwan
  • Taichung, Taiwan
    • Recruiting
    • Department of Psychiatry, China Medical University Hospital
    • Contact: Hsien-Yuan Lane, M.D., Ph.D; Phone Number: 1855 886 4 22052121; Email: hylane@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Have a DSM-5 (American Psychiatric Association) diagnosis of schizophrenia
• Are resistant to adequate treatments of at least two antipsychotics
• 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 12-week trial
• PANSS total score ≥ 70
• 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, stroke, 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: NMDAE plus Placebo; An NMDA enhancer plus Placebo	Drug: NMDAE plus Placebo Cap; Use of an NMDA enhancer plus placebo as a comparator
Experimental: NMDAE plus Anti-inflammatory Agent (AIFA); An NMDA enhancer plus a drug with anti-inflammatory property	Drug: NMDAE plus AIFA; Use of an NMDA enhancer plus a drug with anti-inflammatory property for the treatment of schizophrenia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Positive and Negative Syndrome Scale (PANSS)	Assessment of overall symptoms. Minimum value: 30, maximum value:210, the higher scores mean a worse outcome.	week 0, 2, 4, 6, 9, 12]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impression	Assessment of general impression. Minimum value: 1, maximum value:7, the higher scores mean a worse outcome.	week 0, 2, 4, 6, 9, 12
Global Assessment of Functioning	Assessment of social, occupational, and psychological function. Minimum value: 1, maximum value:100, the higher scores mean better function.	week 0, 2, 4, 6, 9, 12
Quality of Life Scale	Assessment of life quality. Minimum value: 0, maximum value:126, the higher scores mean a better outcome.	week 0, 2, 4, 6, 9, 12
Change of scales for the Assessment of Negative Symptoms (SANS) total score	Assessment of negative symptoms. Minimum value: 0, maximum value:100, the higher scores mean a worse outcome.	0, 2, 4, 6, 9, 12
Positive subscale, Negative subscales, and General Psychopathology subscale of PANSS	PANSS-positive: Assessment of positive symptoms. Minimum value: 7, maximum value:49, the higher scores mean a worse outcome. PANSS-negative: Assessment of negative symptoms. Minimum value: 7, maximum value:49, the higher scores mean a worse outcome. PANSS-general psychopathology: Assessment of general psychopathology. Minimum value: 16, maximum value:112, the higher scores mean a worse outcome	week 0, 2, 4, 6, 9, 12
Hamilton Rating Scale for Depression	Assessment of depressive symptoms. Minimum value: 0, maximum value:52, the higher scores mean a worse outcome.	week 0, 2, 4, 6, 9, 12
Cognitive function	The measure is the composite from multiple measures. Ten cognitive tests for assessment of 7 cognitive domains: speed of processing (assessed by 3 tests: Category Fluency, Trail Marking A, WAIS-III Digit Symbol-Coding);; sustained attention (Continuous Performance Test);; working memory: verbal (digit span) and nonverbal (spatial span);; verbal learning and memory (WMS-III, word listing);; visual learning and memory (WMS-III, visual reproduction);; reasoning and problem solving (WISC-III, Maze);; social cognition (the Mayer-Salovey-Caruso Emotional Intelligence Test [MSCEIT] Version 2)	Week 0, 12

Collaborators and Investigators

• Sponsor: China Medical University Hospital
• Collaborators: Ministry of Science and Technology, Taiwan

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2020
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: June 2, 2021
• First Submitted That Met QC Criteria: June 2, 2021
• First Posted (Actual): June 8, 2021

Study Record Updates

• Last Update Posted (Actual): August 8, 2023
• Last Update Submitted That Met QC Criteria: August 6, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Inflammation; Schizophrenia; NMDA
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: CMUH108-REC1-178

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No