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

Primary Purpose

Ultra High Risk for Psychosis

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Omega-3 fatty acids
Placebo
Sponsored by
Rene Kahn
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Ultra High Risk for Psychosis focused on measuring Ultra-high risk, UHR, psychosis

Eligibility Criteria

13 Years - 20 Years (Child, Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • BioPsyC Biopsychosocial Corporation
  • Department of Child and Adolescent Psychiatry, University of Tübingen
  • Schneider Children's Medical Center
  • Tel Hashomer The Sheba Medical Center
  • Fondazione Santa Lucia
  • Sapienza University of Rome
  • Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht
  • Institute of Clinical Medicine, University of Bergen
  • Hospital Clinic de Barcelona
  • Hospital Infantil Passeig Sant Joan de Deu
  • Hospital General Universitario Gregorio Marañon
  • Idival, University of Cantabria, Cibersam Unidad de investigacion en psiquiatria
  • ZKJP University Zürich
  • Psychiatry, Centre for Clinical Brain Sciences

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Omega-3 fatty acids

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
October 15, 2015
Last Updated
February 13, 2023
Sponsor
Rene Kahn
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1. Study Identification

Unique Protocol Identification Number
NCT02597439
Brief Title
Placebo-controlled Trial in Subjects at Ultra-high Risk for Psychosis With Omega-3 Fatty Acids in Europe
Acronym
PURPOSE
Official Title
Placebo-controlled Trial in Subjects at Ultra-high Risk for Psychosis With Omega-3 Fatty Acids in Europe
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
September 30, 2016 (Actual)
Primary Completion Date
February 1, 2023 (Actual)
Study Completion Date
February 1, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Rene Kahn

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ultra High Risk for Psychosis
Keywords
Ultra-high risk, UHR, psychosis

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
145 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Omega-3 fatty acids
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Omega-3 fatty acids
Other Intervention Name(s)
Fishoil
Intervention Type
Other
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Transition rate
Description
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.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Discontinuation rate
Time Frame
2 years
Title
Symptomatology
Description
Symptomatology will be examined with the CAARMS.
Time Frame
2 years
Title
Psychosocial functioning
Description
As determined by the Social and Occupational Functioning Assessment Scale (SOFAS)
Time Frame
2 years
Title
Cognitive function
Description
Cognitive function is determined by the WAIS
Time Frame
2 years
Title
MRI measures
Description
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.
Time Frame
2 years
Title
Blood levels of bioactive lipids
Description
Assessment of the omega-3 to omega-6 ratio
Time Frame
2 years
Title
Tolerability associated with omega-3 fatty acid treatment
Description
Number of participants with treatment-related adverse events as assessed by the physician.
Time Frame
2 years
Title
Blood levels of (epi)genetic markers
Description
Epigenetic markers of interest include but are not restricted to GAD1 and RELN, which are genes coding for the proteins GAD67 and reelin, respectively.
Time Frame
2 years
Title
Blood levels of immune parameters
Description
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.
Time Frame
2 years
Title
Positive and negative symptoms
Description
Symptomatology will be examined with the Positive and Negative Syndrome Scale (PANSS).
Time Frame
2 years
Title
Level of functioning
Description
Symptomatology will be examined with the Global Assessment of Functioning scale (GAF).
Time Frame
2 years
Title
Clinical Impression
Description
Symptomatology will be examined with the Clinical Global Impression Scale (CGI).
Time Frame
2 years
Title
Level of depression
Description
Symptomatology will be examined with the Beck's Depression Inventory (BDI).
Time Frame
2 years
Title
Role functioning
Description
Determined by the Global Functioning Role (GF:R) scale
Time Frame
2 years
Title
Social functioning
Description
Determined by the Global Functioning Social (GF:S) scale.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
13 Years
Maximum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
René Kahn, Prof. Dr.
Organizational Affiliation
UMC Utrecht
Official's Role
Study Chair
Facility Information:
Facility Name
BioPsyC Biopsychosocial Corporation
City
Vienna
Country
Austria
Facility Name
Department of Child and Adolescent Psychiatry, University of Tübingen
City
Tübingen
Country
Germany
Facility Name
Schneider Children's Medical Center
City
Petach Tikva
Country
Israel
Facility Name
Tel Hashomer The Sheba Medical Center
City
Ramat Gan
Country
Israel
Facility Name
Fondazione Santa Lucia
City
Rome
Country
Italy
Facility Name
Sapienza University of Rome
City
Rome
Country
Italy
Facility Name
Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht
City
Utrecht
Country
Netherlands
Facility Name
Institute of Clinical Medicine, University of Bergen
City
Bergen
Country
Norway
Facility Name
Hospital Clinic de Barcelona
City
Barcelona
Country
Spain
Facility Name
Hospital Infantil Passeig Sant Joan de Deu
City
Barcelona
Country
Spain
Facility Name
Hospital General Universitario Gregorio Marañon
City
Madrid
Country
Spain
Facility Name
Idival, University of Cantabria, Cibersam Unidad de investigacion en psiquiatria
City
Santander
Country
Spain
Facility Name
ZKJP University Zürich
City
Zurich
Country
Switzerland
Facility Name
Psychiatry, Centre for Clinical Brain Sciences
City
Edinburgh
Country
United Kingdom

12. IPD Sharing Statement

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

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