Placebo-controlled Trial in Subjects at Ultra-high Risk for Psychosis With Omega-3 Fatty Acids in Europe

Ultra High Risk for Psychosis Clinical Trial

— PURPOSE  

Official title:

Placebo-controlled Trial in Subjects at Ultra-high Risk for Psychosis With Omega-3 Fatty Acids in Europe

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02597439
• Other study ID #: ABR54654
• Secondary ID: 2015-003503-39
• Status: Completed
• Phase: Phase 4
• Start date: September 30, 2016
• Est. completion date: February 1, 2023

Study information

• Verified date: February 2023
• Source: UMC Utrecht
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 145
• Est. completion date: February 1, 2023
• Est. primary completion date: February 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 13 Years to 20 Years

Eligibility

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.

Related Conditions & MeSH terms

• Mental Disorders
• Psychotic Disorders
• Ultra High Risk for Psychosis

Intervention

Drug:
• Omega-3 fatty acids

Other:
• Placebo

Locations

Country	Name	City	State
Austria	BioPsyC Biopsychosocial Corporation	Vienna
Germany	Department of Child and Adolescent Psychiatry, University of Tübingen	Tübingen
Israel	Schneider Children's Medical Center	Petach Tikva
Israel	Tel Hashomer The Sheba Medical Center	Ramat Gan
Italy	Fondazione Santa Lucia	Rome
Italy	Sapienza University of Rome	Rome
Netherlands	Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht	Utrecht
Norway	Institute of Clinical Medicine, University of Bergen	Bergen
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Infantil Passeig Sant Joan de Deu	Barcelona
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Idival, University of Cantabria, Cibersam Unidad de investigacion en psiquiatria	Santander
Switzerland	ZKJP University Zürich	Zurich
United Kingdom	Psychiatry, Centre for Clinical Brain Sciences	Edinburgh

Sponsors (1)

Lead Sponsor	Collaborator
Rene Kahn

Countries where clinical trial is conducted

Austria,  Germany,  Israel,  Italy,  Netherlands,  Norway,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Transition rate	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.	2 years
Secondary	Discontinuation rate		2 years
Secondary	Symptomatology	Symptomatology will be examined with the CAARMS.	2 years
Secondary	Psychosocial functioning	As determined by the Social and Occupational Functioning Assessment Scale (SOFAS)	2 years
Secondary	Cognitive function	Cognitive function is determined by the WAIS	2 years
Secondary	MRI measures	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.	2 years
Secondary	Blood levels of bioactive lipids	Assessment of the omega-3 to omega-6 ratio	2 years
Secondary	Tolerability associated with omega-3 fatty acid treatment	Number of participants with treatment-related adverse events as assessed by the physician.	2 years
Secondary	Blood levels of (epi)genetic markers	Epigenetic markers of interest include but are not restricted to GAD1 and RELN, which are genes coding for the proteins GAD67 and reelin, respectively.	2 years
Secondary	Blood levels of immune parameters	Immune parameters that are assessed include but are not restricted to interferon-?, interleukin (IL)-1a, IL-1RA, IL-5, IL-10, IL12p40, IL-15, IL-18 and tumour necrosis factor-a.	2 years
Secondary	Positive and negative symptoms	Symptomatology will be examined with the Positive and Negative Syndrome Scale (PANSS).	2 years
Secondary	Level of functioning	Symptomatology will be examined with the Global Assessment of Functioning scale (GAF).	2 years
Secondary	Clinical Impression	Symptomatology will be examined with the Clinical Global Impression Scale (CGI).	2 years
Secondary	Level of depression	Symptomatology will be examined with the Beck's Depression Inventory (BDI).	2 years
Secondary	Role functioning	Determined by the Global Functioning Role (GF:R) scale	2 years
Secondary	Social functioning	Determined by the Global Functioning Social (GF:S) scale.	2 years