The Effect of D-serine as add-on Therapy in Recent-onset Psychosis

Study Overview
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Brief Summary
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In psychotic disorders, negative symptoms and cognitive impairment are difficult to treat with antipsychotics, which are mostly effective for positive symptoms. However, it is important that negative symptoms and cognitive impairment are treated as well, as they both play a large part in the acute episode and long-term course of schizophrenia outcome. Previous studies have used D-serine as add-on treatment in patients with psy-chotic disorders and high-risk patients, with positive results. So far, no study has investigated the effects in a sample of recent-onset psychosis patients. Therefore, this study will include 30 patients (18-50 years old) with recent-onset psychosis. In addition to their regular treatment, patients will receive either D-serine (2 g/d) or placebo for 6 weeks. D-serine is an amino-acid naturally occurring in the brain which is prescription-free available as nutritional supplement. The primary outcome measure is total score on the Positive and Negative Syndrome Scale (PANSS). Secondary measure-ments include PANSS subscales, neurocognitive tests, (f)MRI, and EEG

Official Title
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The Effect of D-serine as add-on Therapy in Recent-onset Psychosis

Conditions
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Psychotic Disorder

Intervention / Treatment
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* Dietary Supplement: D-serine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-50 Recent onset psychosis (< 5 years of overt psychotic symptoms) Able to read and understand study procedures and participant's information Exclusion Criteria: Clozapine use Suicidal ideation Psychotic disorders and symptoms associated with general medical conditions or substance abuse BMI > 30 Renal impairment (history and creatin levels (< 80 ug/L for woman and < 97 ug/L for men)) Hearing impairment Current or past (< 6 months) enrolment in another clinical trial with the primary outcome to improve symptoms Pregnant or lactating women (pregnancy test)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: D-serine group<br>Oral administration of 2g D-serine per day, for 6 weeks. | Dietary Supplement: D-serine<br>* Capsule D-serine<br>|
| Placebo Comparator: Placebo group<br>Oral administration of 2g Placebo (Mannitol) per day, for 6 weeks. | Other: Placebo<br>* Capsule D-serine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total symptom severity | total score on the Positive and Negative Syndrome Scale (PANSS). Lower scores indicate better outcome (min. 30 - max. 120). | change from baseline to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subscales symptom severity | Subscores (5-factor model) on the Positive and Negative Syndrome Scale (PANSS). Lower scores indicate better outcome. | change from baseline to 6 weeks | 
| Symptom severity and treatment response | measured with the Clinical Global Impression Scale (CGI), lower scores indicate a better outcome | change from baseline to 6 weeks | 
| Resting-state microstates | measured with resting-state electroencephalography (EEG). large-scale neural networks are investigated with EEG microstates Ocillations in the theta-band (4-7 Hz) and gamma-band (>30 Hz) will be assessed. measured with resting-state electroencephalography (EEG). Ocillations in the theta-band (4-7 Hz) and gamma-band (>30 Hz) will be assessed. | change from baseline to 6 weeks | 
| Mismatch Negativity (MMN) | measured with EEG | change from baseline to 6 weeks | 
| Intelligence | Part of neurocognitive testing. Higher scores indicate better outcome. | change from baseline to 6 weeks | 
| Attention and processing speed | Part of neurocognitive testing. Higher scores indicate better outcome. | change from baseline to 6 weeks | 
| Executive functioning | Part of neurocognitive testing. Higher scores indicate better outcome. | change from baseline to 6 weeks | 
| Memory | Part of neurocognitive testing. Higher scores indicate better outcome. | change from baseline to 6 weeks |