Clinical trial NCT04745143: Monotherapy of an NMDA Enhancer for Schizophrenia
Official title: Monotherapy of an NMDA Enhancer for Schizophrenia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Schizophrenia
Keywords: Schizophrenia
NMDA
Oxidative stress
Lead sponsor: China Medical University Hospital
Sponsor class: OTHER
Collaborators: name: National Health Research Institutes, Taiwan
First posted: 2021-02-09
Enrollment: 80
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 agent was able to augment antioxidant activity and its adjunctive therapy was better than placebo in reducing clinical symptoms and cognitive deficits and revealed favorable safety in patients with chronic schizophrenia. Of note, a substantial portion of schizophrenia patients refuse or cannot tolerate antipsychotics due to poor response or severe side effects. Therefore, this study aims to examine the efficacy and safety of an NMDA enhancer (NMDAE) as a monotherapy for the treatment of schizophrenia.

Detailed description: Several lines of evidence suggest that schizophrenia is associated with accelerated aging and oxidative stress may play a role. Cognitive deficits are core symptoms of accelerated aging in patients with schizophrenia and the most difficult domain to treat. Current antipsychotics have limited, if any, efficacy for cognitive function. Previous studies found that some NMDA-enhancing agent was able to augment antioxidant activity and its adjunctive therapy was better than placebo in reducing not only clinical symptoms but also cognitive deficits and revealed favorable safety in patients with chronic schizophrenia. Of note, a substantial portion of schizophrenia patients refuse or cannot tolerate antipsychotics due to poor response or severe side effects. This study aims to examine the efficacy and safety of NMDAE monotherapy for the treatment of schizophrenia. The investigators enroll patients with schizophrenia who refuse or are unable to tolerate antipsychotics due to poor response or adverse effects into a 6-week randomized, double-blind trial to receive monotherapy of NMDAE or placebo. The investigators biweekly measure clinical performances and side effects. Cognitive functions are assessed at baseline and at endpoint of treatment by a battery of tests. The efficacies of NMDAE and 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
* Refuse or are unable to tolerate antipsychotics due to poor response or adverse effects
* PANSS total score ≥ 60
* Free of antipsychotic drugs for at least 1 week
* Agree to participate in the study and provide informed consent

Exclusion Criteria:

* Current substance abuse or history of substance dependence in the past 3 months
* History of epilepsy, head trauma, stroke or other serious medical or neurological illness which may interfere with the study
* Use of depot antipsychotic in the past 3 months;
* Clinically significant laboratory screening 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
measure: Change of scales for the Assessment of Negative Symptoms (SANS) total score
timeFrame: week 0, 2, 4, 6
Secondary outcomes:
measure: Positive subscale, Negative subscales, and General Psychopathology subscale of Positive and Negative Syndrome Scale (PANSS)
timeFrame: week 0, 2, 4, 6
measure: Clinical Global Impression
timeFrame: week 0, 2, 4, 6
measure: Global Assessment of Functioning
timeFrame: week 0, 2, 4, 6
measure: Hamilton Rating Scale for Depression
timeFrame: week 0, 2, 4, 6
measure: Quality of Life Scale
timeFrame: week 0, 2, 4, 6
measure: Cognitive function
timeFrame: Week 0, 6
Other outcomes:
Locations:
city: Taichung
country: Taiwan
facility: Department of Psychiatry, China Medical University Hospital
Study officials:
References: