Placebo-controlled Trial in Subjects at Ultra-high Risk for Psychosis With Omega-3 Fatty Acids in Europe
- Conditions
- Ultra High Risk for Psychosis
- Interventions
- Other: Placebo
- Registration Number
- NCT02597439
- Lead Sponsor
- Rene Kahn
- Brief Summary
The purpose of this study is to determine whether omega-3 fatty acids are effective in the prevention of psychosis in individuals at ultra-high risk for psychosis.
- Detailed Description
PURPOSE is a randomized double-blind placebo-controlled study. Main objective is to assess the effectivity of omega-3 fatty acid treatment in the prevention of psychosis. The primary outcome measure is the rate of transition to psychosis as determined through CAARMS. Subjects in the age range of 13-20 years with a higher chance of developing psychosis, as determined by the CAARMS, are treated for 6 months with omega-3 fatty acids or placebo. This study in conducted at 14 sites in 9 countries.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 145
- Written informed consent of the subject. For individuals younger than 18 years of age the parents / legal representatives need to give consent, and the subject can provide assent (whether the latter is required depends on local laws and regulations).
- UHR diagnosis as made using the Comprehensive Assessment of At-Risk Mental States (CAARMS) (Yung et al., 2005). Subjects have to meet one or more of the following criteria: (a) attenuated psychotic symptoms, (b) brief limited intermittent psychotic symptoms (a history of one or more episodes of frank psychotic symptoms that resolved spontaneously within 1 week in the past year), or (c) either the presence of schizotypal personality disorder or a family history of psychosis in a first-degree relative, all three together with a recent decline in function.
- Any clinically significant medical condition that may influence the results of the trial or affect the ability to take part in a trial.
- Laboratory screening values considered clinically relevant by a medical doctor for transaminases, thyroid hormones or coagulation parameters
- Current or past DSM-IV diagnosis of psychosis, as measured with K-SADS-PL
- Current treatment with an antipsychotic or mood-stabilising agent
- Intake of an antipsychotic or mood-stabilising agent in the two weeks prior to study inclusion
- Intake of an antipsychotic agent equivalent to a total haloperidol use of >50 mg in the six months prior to study inclusion
- A first-degree relative (i.e. parents, offspring or siblings) participating in this study
- UHR diagnosis on the basis of attenuated psychotic symptoms that are entirely explained by acute intoxication
- Current aggression or dangerous behaviour (PANSS G14 score 5 or above)
- Current suicidality / self-harm (PANSS G6 score 7)
- Current DSM-IV diagnosis of alcohol or substance dependence as measured with K-SADS-PL
- Any current or previous neurological disorder, including epilepsy
- History of head injury resulting in unconsciousness lasting at least 1 hour
- IQ < 70
- More than 4 weeks of regular omega-3 supplementation (>2 daily capsules standard strength providing >600 mg combined EPA/DHA) within the last 6 months.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Subjects will be treated daily with placebo for six months. Placebo capsules will contain a 1:1 combination of coconut oil and medium chain triglycerides because these do not contain polyunsaturated fatty acids and have no impact on omega-3 fatty acid metabolism. Placebo capsules also contain the same amount of vitamin E as the omega-3 capsules and 1% fish oil to mimic flavour and taste. Omega-3 fatty acids Omega-3 fatty acids Subjects will be treated daily with 1.2 gram omega-3 polyunsaturated fatty acids (720 mg eicosapentaenoic acid (EPA) and 480 mg Docosahexaenoic acid(DHA)) for six months.
- Primary Outcome Measures
Name Time Method Transition rate 2 years To compare transition rates to psychosis during 2 years of follow-up between the omega-3 fatty acids arm and the placebo arm. Starting point is the first administration of medication at the end of visit 2. Endpoint is the moment that a UHR subject makes a transition to psychosis according to the CAARMS criteria.
- Secondary Outcome Measures
Name Time Method Discontinuation rate 2 years Symptomatology 2 years Symptomatology will be examined with the CAARMS.
Cognitive function 2 years Cognitive function is determined by the WAIS
Tolerability associated with omega-3 fatty acid treatment 2 years Number of participants with treatment-related adverse events as assessed by the physician.
Blood levels of (epi)genetic markers 2 years Epigenetic markers of interest include but are not restricted to GAD1 and RELN, which are genes coding for the proteins GAD67 and reelin, respectively.
Positive and negative symptoms 2 years Symptomatology will be examined with the Positive and Negative Syndrome Scale (PANSS).
Psychosocial functioning 2 years As determined by the Social and Occupational Functioning Assessment Scale (SOFAS)
MRI measures 2 years Brain structure and function are measured in three MRI sessions, consisting of structural MRI, resting state functional MRI, Diffusion Tensor Imaging (DTI), and functional MRI during reward processing.
Level of functioning 2 years Symptomatology will be examined with the Global Assessment of Functioning scale (GAF).
Clinical Impression 2 years Symptomatology will be examined with the Clinical Global Impression Scale (CGI).
Role functioning 2 years Determined by the Global Functioning Role (GF:R) scale
Blood levels of bioactive lipids 2 years Assessment of the omega-3 to omega-6 ratio
Blood levels of immune parameters 2 years Immune parameters that are assessed include but are not restricted to interferon-γ, interleukin (IL)-1α, IL-1RA, IL-5, IL-10, IL12p40, IL-15, IL-18 and tumour necrosis factor-α.
Level of depression 2 years Symptomatology will be examined with the Beck's Depression Inventory (BDI).
Social functioning 2 years Determined by the Global Functioning Social (GF:S) scale.
Trial Locations
- Locations (14)
Institute of Clinical Medicine, University of Bergen
🇳🇴Bergen, Norway
ZKJP University Zürich
🇨🇭Zurich, Switzerland
Tel Hashomer The Sheba Medical Center
🇮🇱Ramat Gan, Israel
Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht
🇳🇱Utrecht, Netherlands
Fondazione Santa Lucia
🇮🇹Rome, Italy
BioPsyC Biopsychosocial Corporation
🇦🇹Vienna, Austria
Schneider Children's Medical Center
🇮🇱Petach Tikva, Israel
Department of Child and Adolescent Psychiatry, University of Tübingen
🇩🇪Tübingen, Germany
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Psychiatry, Centre for Clinical Brain Sciences
🇬🇧Edinburgh, United Kingdom
Idival, University of Cantabria, Cibersam Unidad de investigacion en psiquiatria
🇪🇸Santander, Spain
Hospital Infantil Passeig Sant Joan de Deu
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Sapienza University of Rome
🇮🇹Rome, Italy