Clinical trial NCT04917302: Combination of NMDA-enhancing and Anti-inflammatory Treatments for Schizophrenia
Official title: Combination of NMDA-enhancing and Anti-inflammatory Treatments for Schizophrenia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Schizophrenia
Keywords: Schizophrenia
NMDA
Inflammation
Lead sponsor: China Medical University Hospital
Sponsor class: OTHER
Collaborators: name: Ministry of Science and Technology, Taiwan
First posted: 2021-06-08
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change of Positive and Negative Syndrome Scale (PANSS)
timeFrame: week 0, 2, 4, 6, 9, 12]
Secondary outcomes:
measure: Change of scales for the Assessment of Negative Symptoms (SANS) total score
timeFrame: 0, 2, 4, 6, 9, 12
measure: Positive subscale, Negative subscales, and General Psychopathology subscale of PANSS
timeFrame: week 0, 2, 4, 6, 9, 12
measure: Clinical Global Impression
timeFrame: week 0, 2, 4, 6, 9, 12
measure: Global Assessment of Functioning
timeFrame: week 0, 2, 4, 6, 9, 12
measure: Hamilton Rating Scale for Depression
timeFrame: week 0, 2, 4, 6, 9, 12
measure: Quality of Life Scale
timeFrame: week 0, 2, 4, 6, 9, 12
measure: Cognitive function
timeFrame: Week 0, 12
Other outcomes:
Locations:
city: Taichung
country: Taiwan
facility: Department of Psychiatry, China Medical University Hospital
Study officials:
References: