Omega-3 Fatty Acids Efficacy in First-episode of Schizophrenia

Study Overview
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Brief Summary
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There is accumulating experimental evidence to suggest the role of essential fatty acids (EFA) in neuronal migration, pruning and synaptic plasticity. These processes are implied to be dysfunctional on early stages of schizophrenia, according to neurodevelopmental hypothesis. Numerous epidemiological and clinical trial data support the benefit of EFA rich diets in reducing symptoms in schizophrenia. An EFA rich diet might be of particular importance at the beginning of the illness. As a relatively safe option, EFA supplementation would be a preferable add on therapy in treating individuals with a first episode of schizophrenia (FES) and a short duration of psychotic symptoms. No long term follow-up studies of EFA supplementation in FES patients were carried out. The demonstration of the efficacy of the prophylactic properties of EFAs in relapse prevention in FES patients would be a strong basis for further studies and prescribing EFAs for a large population of patients who are in the early stages of that debilitating illness.

Official Title
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Omega-3 Fatty Acids in First-episode Schizophrenia - a Randomized Controlled Study of Efficacy and Relapse Prevention (OFFER). Rationale, Design, and Methods.

Conditions
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Schizophrenia

Intervention / Treatment
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* Dietary Supplement: essential fatty acids
* Dietary Supplement: olive oil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with schizophrenia using Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria Patients aged between 16-35 years Signed informed consent (parallel parents consent for individuals under 18 years of age) Exclusion Criteria: Patients taking fish oil supplements (a washout period of 6 months is required) Patients diagnosed with epilepsy or suffering from epileptic seizures Patients receiving anticoagulant medication e.g., Warfarin Patients receiving psychotherapy Chronic somatic diseases Psychoactive substance dependence Pregnancy and lactation Mental retardation or diagnosed organic brain injury

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 35 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: essential fatty acids<br>The experimental treatment is a food supplement containing fish oil. The daily dose of 4 capsules provides 1320 mg of eicosapentaenoic acid and 880 mg of docosahexaenoic acid, 26 weeks intervention | Dietary Supplement: essential fatty acids<br>* Yellow capsules containing eicosapentaenoic acid, docosahexaenoic acid (active)<br>|
| Placebo Comparator: olive oil<br>Placebo capsules contain olive oil and trace amount of fish oil to assure comparable taste, 26 weeks intervention | Dietary Supplement: olive oil<br>* Yellow capsules containing olive oil (placebo)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary outcome measure will be the efficacy of n-3 PUFA in reducing psychopathology in first-episode schizophrenia. | The Positive and Negative Syndrome Scale [64] will be used to assess the efficacy of EPA+DHA supplementation in reducing symptom severity in first-episode schizophrenia after 8 and 26 weeks of supplementation. The main outcome measure will be the change in symptom severity from baseline to week 26. Baseline PANSS total score will be subtracted from PANSS score obtained after 26 weeks, resulting in the degree of change observed in the study. | 8 and 26 weeks of supplementation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse rate - Positive and Negative Syndrome Scale (PANSS) defined schizophrenia relapse |  | 26 weeks intervention plus 26 weeks observation | 
| PANSS total, positive, negative and general psychopathology subscales |  | Baseline, 1, 2, 4, 6, 8, 16, 26, 52 weeks | 
| Calgary Depression Scale for Schizophrenia (CDSS) |  | Baseline, 1, 2, 4, 6, 8, 16, 26, 52 weeks | 
| Clinical Global Impression (CGI) |  | Baseline, 1, 2, 4, 6, 8, 16, 26, 52 weeks | 
| Global Assessment of Functioning (GAF) |  | Baseline, 1, 2, 4, 6, 8, 16, 26, 52 weeks | 
| A white matter directional organization metric: fractional anisotropy (FA) measured in two areas: corpus callosum and uncinate fasciculus |  | Baseline, 26 weeks | 
| Cognitive performance using composite battery of neuropsychologic tests |  | Baseline, 8 and 26 weeks | 
| Niacin Flush Skin Test |  | Baseline, 8 and 26 weeks | 
| Side effects profile according to self-prepared questionnaire |  | Baseline, 4, 8, 26 | 
| Lymphocyte telomerase activity |  | Baseline, 8 and 26 weeks | 
| Equivalent doses of antipsychotics used |  | Baseline, 1, 2, 4, 6, 8, 16, 26 and 52 weeks | 
| Grey matter volume: a voxel based structural MRI assessment |  | Baseline, 8 and 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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early psychosis, chronic schizophrenia, first episode psychosis, omega-3 and omega-6 essential fatty acids, relapse prevention, efficacy