Ultra High Risk for Psychosis
Conditions
Keywords
Ultra-high risk, UHR, psychosis
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.
Interventions
DRUGOmega-3 fatty acids
OTHERPlacebo
Sponsors
Rene Kahn
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
13 Years to 20 Years
Healthy volunteers
Yes
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Discontinuation rate | 2 years | — |
| Symptomatology | 2 years | Symptomatology will be examined with the CAARMS. |
| Psychosocial functioning | 2 years | As determined by the Social and Occupational Functioning Assessment Scale (SOFAS) |
| Cognitive function | 2 years | Cognitive function is determined by the WAIS |
| 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. |
| Blood levels of bioactive lipids | 2 years | Assessment of the omega-3 to omega-6 ratio |
| Tolerability associated with omega-3 fatty acid treatment | 2 years | Number of participants with treatment-related adverse events as assessed by the physician. |
| Positive and negative symptoms | 2 years | Symptomatology will be examined with the Positive and Negative Syndrome Scale (PANSS). |
| 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). |
| Level of depression | 2 years | Symptomatology will be examined with the Beck's Depression Inventory (BDI). |
| Role functioning | 2 years | Determined by the Global Functioning Role (GF:R) scale |
| Social functioning | 2 years | Determined by the Global Functioning Social (GF:S) scale. |
| 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. |
Countries
Austria, Germany, Israel, Italy, Netherlands, Norway, Spain, Switzerland, United Kingdom
Outcome results
None listed