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

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.

Study Overview

• Status: Completed
• Conditions: Ultra High Risk for Psychosis
• Intervention / Treatment: Other: Placebo; Drug: Omega-3 fatty acids

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.

• Study Type: Interventional
• Enrollment (Actual): 145
• Phase: Phase 4

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 20 years (ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 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.	Drug: Omega-3 fatty acids; Other Names: Fishoil
PLACEBO_COMPARATOR: 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.	Other: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Discontinuation rate		2 years
Symptomatology	Symptomatology will be examined with the CAARMS.	2 years
Psychosocial functioning	As determined by the Social and Occupational Functioning Assessment Scale (SOFAS)	2 years
Cognitive function	Cognitive function is determined by the WAIS	2 years
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
Blood levels of bioactive lipids	Assessment of the omega-3 to omega-6 ratio	2 years
Tolerability associated with omega-3 fatty acid treatment	Number of participants with treatment-related adverse events as assessed by the physician.	2 years
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
Blood levels of immune parameters	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.	2 years
Positive and negative symptoms	Symptomatology will be examined with the Positive and Negative Syndrome Scale (PANSS).	2 years
Level of functioning	Symptomatology will be examined with the Global Assessment of Functioning scale (GAF).	2 years
Clinical Impression	Symptomatology will be examined with the Clinical Global Impression Scale (CGI).	2 years
Level of depression	Symptomatology will be examined with the Beck's Depression Inventory (BDI).	2 years
Role functioning	Determined by the Global Functioning Role (GF:R) scale	2 years
Social functioning	Determined by the Global Functioning Social (GF:S) scale.	2 years

Collaborators and Investigators

• Sponsor: Rene Kahn

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 30, 2016
• Primary Completion (ACTUAL): February 1, 2023
• Study Completion (ACTUAL): February 1, 2023

Study Registration Dates

• First Submitted: October 15, 2015
• First Submitted That Met QC Criteria: November 3, 2015
• First Posted (ESTIMATE): November 5, 2015

Study Record Updates

• Last Update Posted (ESTIMATE): February 14, 2023
• Last Update Submitted That Met QC Criteria: February 13, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: psychosis; Ultra-high risk; UHR
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Psychotic Disorders; Mental Disorders
• Other Study ID Numbers: ABR54654; 2015-003503-39 (EUDRACT_NUMBER)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No