SchizophreniaPhase 4NCT00396643
Indicated Prevention With Omega-3 Fatty Acids in Adolescents With 'At-Risk-Mental-State' for Psychosis
A Phase 4 study testing Omega 3 fatty acids in people with Schizophrenia and Prodrome, run by Medical University of Vienna at 1 site in Austria.
Trial summary
Early intervention in psychosis might be associated with better outcomes. However, intervention in the pre-psychotic phase has been questioned as, using current criteria, only 20-50% of individuals classified as prodromal develop a psychotic disorder within a 1-2 years period. Read more about this study
- Who is it for?
- Ages 13 to 25 years
- Conditions the study is for
- Schizophrenia, Prodrome
- What is being tested?
- Omega 3 fatty acids
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 81 participants
- Where
- 1 siteAustria
- Study dates
- May 2004to Jun 2007
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- /written informed consent (for individuals under 18 written informed consent of at least one of the parents is required),
- /age between 13 and 25 years,
- /ARMS as classified by the PACE criteria (Yung et al., 1998)
- PACE criteria for ARMS include one or more of following characteristics which must have occurred within the last 12 months:
- Frank psychotic symptoms < 1 week (Transient psychosis group)
- Attenuated psychotic symptoms > 1 week, > 2 times per week
- Decline in global function (drop in GAF of > 30%) plus family history of psychosis or individual has schizotypal personality disorder To operationalize PACE criteria duration and severity ratings of psychotic symptoms will be performed using the Positive and Negative Syndromes of Schizophrenia Scale (PANSS) (Kay et al., 1987) applying following cut-off scores, following Morrison et al (2002): Ad 1) Transient psychosis is defined with the presence of symptoms that score 4 or more on hallucinations, 4 or more on delusions, or 5 or more on conceptual disorganizations, last less than one week and resolve without antipsychotic medication. Ad 2) Attenuated psychotic symptoms are defined by the presence of symptoms that score 3 on delusions, 2-3 on hallucinations, 3-4 on suspiciousness or 3-4 on conceptual disorganization.
Who cannot join
- /Acute suicidal behaviour, aggressive behaviour (PANSS hostility, suicidality = 7),
- /Drug abuse that contributed decisively to the presentation of the index episode, (dependency on morphine, cocaine, amphetamine, but not THC),
- /Alcohol abuse if considered as major problem,
- /Epilepsy,
- /Mental Retardation (IQ<80),
- /Pregnancy and lactation,
Show all 13Show fewer
- /Structural changes in MRI or CT scan (e.g., tumours), expect for enlargement of ventricles or sulci,
- /Previous history of antipsychotic drug (>1 week) or mood stabilizer treatment,
- /Laboratory values more than 10% outside the normal range for transaminases, CRP or bleeding parameters,
- /Individuals with organic brain syndrome,
- /Individuals who are taking anticoagulants,
- /Individuals who are taking omega 3 supplements, currently or within 8 weeks of being included in the trial,
- /Individuals who have other, severe, intercurrent illness which in the opinion of the investigator may put them at risk or influence the results of the trial or affect ability to take part in the trial.
Trial locations and contacts
1 site in 1 country.
Austria1 site
Medical University of Vienna, Department of Child and Adolescent Psychiatry
Vienna, State of Vienna, 1090
About this study
Official title: Indicated Prevention With Omega-3 Fatty Acids in Adolescents With 'At-Risk-Mental-State' for Psychosis: A Randomised, Double Blind, Placebo-Controlled Treatment Trial
Early intervention in psychosis might be associated with better outcomes. However, intervention in the pre-psychotic phase has been questioned as, using current criteria, only 20-50% of individuals classified as prodromal develop a psychotic disorder within a 1-2 years period. Treatment agents investigated in the pre-psychotic phase of schizophrenia and other psychotic disorders should, therefore, not have major side effects. This proposal investigates omega-3 fatty acids (1.2 gramm per day eicosapentaenoic acid/docosahexaenoic acid;EPA/DHA) as a beneficial and possible preventive therapeutic agent in young people at ultra high-risk for developing a psychotic disorder.
Read the detailed description
- Aims of the study The principal aim is to test if 1.2 g/day EPA/DHA can prevent transition to first-episode psychosis in 13-25 year old ultra-high risk individuals. Specifically we propose to investigate:
- The clinical effects of EPA/DHA supplementation as an adjunct to standard therapy in individuals with 'At-Risk Mental State' (ARMS) for psychosis as defined by the PACE criteria (Yung et al., 1998).
- Lipid metabolism in peripheral tissue pre/post treatment by 1./analyzing bioactive lipid composition of red-blood cell membranes, 2./measuring phospholipase A2 (cPLA2) activity in serum (the enzyme responsible for the cleavage of arachidonic acid (AA) and other precursors of bioactive lipids from glycerophospholipids (GPL) and 3./the topical niacin flush test (a clinical test of the AA-prostaglandin D2 cascade).
- Background and evidence that bioactive lipids are altered in schizophrenia and can be influenced by EPA/DHA supplementation There is suggestion that early intervention in psychosis might be associated with better outcomes (Norman \& Malla, 2001). However, intervention in the pre-psychotic phase has been questioned as, using current criteria, only 20-50% of individuals classified as prodromal develop a psychotic disorder within a 1-2 years period (McGlashan et al., 2001). Treatment agents investigated in the pre-psychotic phase of schizophrenia and other psychotic disorders should, therefore, not have major side effects. This proposal introduces EPA/DHA, two omega-3 essential fatty acids (EFA), as a beneficial and possible preventative therapeutic agent in young people at ultra high-risk for developing a psychotic disorder. Bioactive lipids and their role in the brain Bioactive lipids are molecules that have both intra- and intercellular roles, including mediation, modulation and control of neurobiological processes, such as ion channel and receptor activity, neurotransmitter release, synaptic plasticity, second messenger pathways and neuronal gene expression (Agranoff et al., 1998). Emphasis has been placed on AA and its metabolites, known collectively as eicosanoids. A major proportion of lipids in the brain consist of bioactive lipids such as AA and its metabolites, also referred to as EFA, which are mainly bound to GPL. Bioactive lipids are released through direct and indirect enzymatic pathways (e.g., phospholipases) from membrane GPL. AA is a precursor of prostaglandins, thromboxanes, leukotriens (5-HpETE) and prostacyclins. Animal studies and preliminary studies in humans have shown an association between bioactive lipid metabolism, behaviour and cognition (Zimmer et al., 2000). Reduced membrane EFA in schizophrenia Abnormal membrane GPL EFA metabolism has been suggested to contribute to the aetiopathophysiology of schizophrenia. A recent review of 15 published studies confirmed a depletion of bioactive lipids in cell membranes of patients with schizophrenia (Fenton et al., 2000). The most consistent findings were reductions in AA and its precursors, and these were independent of drug treatment (Yao et al., 1996). Reductions in AA and its precursors have also been found in post mortem brains of patients with schizophrenia, relative to normal control brains [Yao et al., 2000]. Yao and van Kammen (1996) suggested that defective uptake of AA into membrane GPL was a possible aetiopathological mechanism in schizophrenia, whereas Peet et al. (1996), who reported an additional increase of EFA peroxidation products, suggested there was increased breakdown of membrane GPL. Khan et al. (2002) reported on erythrocyte membrane EFA levels and levels of plasma lipid peroxides, products of damaged EFAs, in drug-naive patients within +/-4.5 days of onset of psychosis. The levels of EFAs, particularly AA and docosahexaenoic acid (DHA) were significantly lower in drug-naive patients at the onset of psychosis compared to matched normal controls. These lower EFA levels were associated with significantly higher levels of lipid peroxides in patients. The levels of AA and DHA were also lower and lipid peroxides higher in chronic medicated patients than normal controls. Interestingly in context with this proposal, EFA levels were higher in chronic medicated patients than drug-naive first-episode patients. Khan et al. concluded that these findings could indicate that lower membrane AA and DHA most likely predate the illness and probably contribute to the onset of illness. The lipid peroxidation data suggest that possible increased oxidative stress may be one of the mechanisms of reduced membrane EFAs. The findings also imply that supplementation of EFAs and/or antioxidants might provide effective treatments for early psychosis. This view is supported by Horrobin et al. (2002) who showed that increase in red cell AA levels resulted from treatment with the optimal levels of EPA and that, clinical improvement was highly significantly positively correlated with rises in red cell membrane AA in individuals with schizophrenia. Treatment studies in schizophrenia Three randomized controlled treatment studies conducted over 12 weeks found 2g/day EPA significantly more effective than placebo in reducing psychopathological symptoms in individuals with schizophrenia (Peet et al., 2001; Emsley et al., 2002). Symptom improvements in those studies were both, clinically relevant and statistically significant. A dose-ranging exploratory study of the effects of EPA in individuals with schizophrenia who experienced persistent symptoms found 2 g EPA/day significantly more effective in reducing symptom scores on psychiatric rating scales than 1g and 4g EPA/day (Peet et al., 2002). On the other hand, Fenton et al. (2002) investigated augmentation of neuroleptics with 3 g/day of EPA on symptoms and cognition in patients with schizophrenia or schizoaffective disorder and reported a negative finding. The patients in Fenton et al.s' study had, however, been ill for two decades and had substantial symptoms, despite treatment with newer neuroleptics, including clozapine. The patients described as benefiting from EPA in the other studies were younger and had a shorter duration of illness. It must be emphasized that in all EPA treatment studies, no treatment-related side effects or adverse biochemical or haematological effects have been observed. EPA proved safe to administer to schizophrenic patients as an adjunct therapy. EPA did not cause side effects other than mild gastrointestinal symptoms by itself, nor did it enhance the side effects of existing drugs. Patients found EPA highly tolerable. The proportion of patients who completed 12 weeks (89%) compares favourably with mean withdrawal rates of 54% in the novel neuroleptic groups and 67% in the placebo groups in trials in the FDA database (Peet et al., 2002). Acceptance of a substance which is normally found in the human body without significant side effects, with a potency potentially similar to the antipsychotic drugs in the early phase of psychotic disorders could contribute to reduce the duration of untreated psychosis and to increase compliance.
- Study design We will use a prospective, randomized, double-blind, placebo-controlled, single-centre study design. Eighty one individuals aged 13-25 will be randomly assigned in two treatment conditions at the University Clinic for Child and Adolescent Neuropsychiatry, Vienna, Austria. Randomization codes will be generated and stored off site. The treatment groups will receive 1.2 gramm per day EPA/DHA or placebo for 12 weeks. Follow-up assessments will be conducted at 1,2,3,4,8,12,26,and 52 weeks. All patients will receive standard treatment, which includes management by a psychiatrist or resident psychiatrist and non-neuroleptic pharmacotherapy as clinically indicated.
- Conditions
- Schizophrenia, Prodrome
- Being tested
- Omega 3 fatty acids
- Keywords
- Ultra-High Risk, Psychosis, Schizophrenia, Omega-3 fatty acids, RCT
- Medical subject headings
- Schizophrenia, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Omega 3 fatty acidsDrug
The active treatment is a supplement of yellow gelatin 0.5 g fish oil capsules. The daily dose of 4 (2x2) capsules provides 700 mg of eicosapentaenoic acid and 500 mg of docosahexaenoic acid, and 10 mg of Vitamin E. Placebo treatment comprises coconut oil capsules, carefully matched with the active treatment with respect to both appearance and flavor, also containing 10 mg Vitamin E, and 10 mg of fish oil to mimic taste. Coconut oil was chosen as placebo because it does not contain polyunsaturated fatty acids and has no impact on n-3 fatty acid metabolism. The intervention period is 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Not described Receives: Drug: Omega 3 fatty acids |
| B | Placebo comparator | Coconut oil Receives: Drug: Omega 3 fatty acids |
What is being measured
The primary outcome is the main question the study is designed to answer.
Transition to PANSS defined first-episode psychosis
Measured: Baseline, 1, 2, 3, 4, 8, 12 weeks, 6, and 12 months
Secondary outcomes (5)
PANSS positive, negative, and global subscales
Measured: Baseline, 1, 2, 3, 4, 8, 12 weeks, 6, and 12 months
MADRS
Measured: Baseline, 1, 2, 3, 4, 8, 12 weeks, 6, and 12 months
GAF
Measured: Baseline, 1, 2, 3, 4, 8, 12 weeks, 6, and 12 months
UKU
Measured: Baseline, 1, 2, 3, 4, 8, 12 weeks
Lipid metabolism in peripheral tissue pre/post treatment
Measured: Baseline, 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2006 (estimated)
- Study startMay 2004
- Primary completionJun 2007
- Study completionJun 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Collaborators
- Stanley Medical Research Institute
- Investigators
- G Paul Amminger, MD, Principal investigator, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00396643
- Sponsor's protocol ID
- SMRI 03T-315
- Other IDs
- FA765Z0003, EK Nr: 415/2002
- Status last verified
- Dec 2007
- First submitted
- 6 Nov 2006
- Last updated
- 27 Dec 2007
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Berger GE, Proffitt TM, McConchie M, et al. Ethyl-Eicosapentaenoic acid in first episode psychosis: A randomized, placebo-controlled trial. Journal of Clinical Psychiatry 2007; in press Berger GE, Wood SJ, Wellard RM, et al. In vivo brain effects of ethyl-eicosapentaenoic acid in early psychosis. A 1H-MRS study. Neuropsychopharmacology 2007;in press.
Smesny S, Milleit B, Schaefer MR, Hesse J, Schlogelhofer M, Langbein K, Hipler UC, Berger M, Cotter DR, Sauer H, McGorry PD, Amminger GP. Effects of omega-3 PUFA on immune markers in adolescent individuals at ultra-high risk for psychosis - Results of the randomized controlled Vienna omega-3 study. Schizophr Res. 2017 Oct;188:110-117. doi: 10.1016/j.schres.2017.01.026. Epub 2017 Jan 23.
PubMed 28126360Focking M, Dicker P, Lopez LM, Cannon M, Schafer MR, McGorry PD, Smesny S, Cotter DR, Amminger GP. Differential expression of the inflammation marker IL12p40 in the at-risk mental state for psychosis: a predictor of transition to psychotic disorder? BMC Psychiatry. 2016 Sep 20;16(1):326. doi: 10.1186/s12888-016-1039-7.
PubMed 27650124Amminger GP, Chanen AM, Ohmann S, Klier CM, Mossaheb N, Bechdolf A, Nelson B, Thompson A, McGorry PD, Yung AR, Schafer MR. Omega-3 fatty acid supplementation in adolescents with borderline personality disorder and ultra-high risk criteria for psychosis: a post hoc subgroup analysis of a double-blind, randomized controlled trial. Can J Psychiatry. 2013 Jul;58(7):402-8. doi: 10.1177/070674371305800705.
PubMed 23870722Amminger GP, Schafer MR, Papageorgiou K, Klier CM, Cotton SM, Harrigan SM, Mackinnon A, McGorry PD, Berger GE. Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Arch Gen Psychiatry. 2010 Feb;67(2):146-54. doi: 10.1001/archgenpsychiatry.2009.192.
PubMed 20124114
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Indicated Prevention With Omega-3 Fatty Acids in Adolescents With 'At-Risk-Mental-State' for Psychosis: A Randomised, Double Blind, Placebo-Controlled Treatment Trial
- ClinicalTrials.gov ID
- NCT00396643
- Acronym / sponsor ID
- SMRI 03T-315
- Conditions
- Schizophrenia, Prodrome
- Keywords
- Ultra-High Risk, Psychosis, Schizophrenia, Omega-3 fatty acids, RCT
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Collaborators
- Stanley Medical Research Institute
- Study start
- May 2004
- Primary completion
- Jun 2007 (actual)
- Study completion
- Jun 2007 (actual)
- First posted
- 7 Nov 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Early intervention in psychosis might be associated with better outcomes. However, intervention in the pre-psychotic phase has been questioned as, using current criteria, only 20-50% of individuals classified as prodromal develop a psychotic disorder within a 1-2 years period. Treatment agents investigated in the pre-psychotic phase of schizophrenia and other psychotic disorders should, therefore, not have major side effects. This proposal investigates omega-3 fatty acids (1.2 gramm per day eicosapentaenoic acid/docosahexaenoic acid;EPA/DHA) as a beneficial and possible preventive therapeutic agent in young people at ultra high-risk for developing a psychotic disorder.
Detailed description
- Aims of the study The principal aim is to test if 1.2 g/day EPA/DHA can prevent transition to first-episode psychosis in 13-25 year old ultra-high risk individuals. Specifically we propose to investigate:
- The clinical effects of EPA/DHA supplementation as an adjunct to standard therapy in individuals with 'At-Risk Mental State' (ARMS) for psychosis as defined by the PACE criteria (Yung et al., 1998).
- Lipid metabolism in peripheral tissue pre/post treatment by 1./analyzing bioactive lipid composition of red-blood cell membranes, 2./measuring phospholipase A2 (cPLA2) activity in serum (the enzyme responsible for the cleavage of arachidonic acid (AA) and other precursors of bioactive lipids from glycerophospholipids (GPL) and 3./the topical niacin flush test (a clinical test of the AA-prostaglandin D2 cascade).
- Background and evidence that bioactive lipids are altered in schizophrenia and can be influenced by EPA/DHA supplementation There is suggestion that early intervention in psychosis might be associated with better outcomes (Norman \& Malla, 2001). However, intervention in the pre-psychotic phase has been questioned as, using current criteria, only 20-50% of individuals classified as prodromal develop a psychotic disorder within a 1-2 years period (McGlashan et al., 2001). Treatment agents investigated in the pre-psychotic phase of schizophrenia and other psychotic disorders should, therefore, not have major side effects. This proposal introduces EPA/DHA, two omega-3 essential fatty acids (EFA), as a beneficial and possible preventative therapeutic agent in young people at ultra high-risk for developing a psychotic disorder. Bioactive lipids and their role in the brain Bioactive lipids are molecules that have both intra- and intercellular roles, including mediation, modulation and control of neurobiological processes, such as ion channel and receptor activity, neurotransmitter release, synaptic plasticity, second messenger pathways and neuronal gene expression (Agranoff et al., 1998). Emphasis has been placed on AA and its metabolites, known collectively as eicosanoids. A major proportion of lipids in the brain consist of bioactive lipids such as AA and its metabolites, also referred to as EFA, which are mainly bound to GPL. Bioactive lipids are released through direct and indirect enzymatic pathways (e.g., phospholipases) from membrane GPL. AA is a precursor of prostaglandins, thromboxanes, leukotriens (5-HpETE) and prostacyclins. Animal studies and preliminary studies in humans have shown an association between bioactive lipid metabolism, behaviour and cognition (Zimmer et al., 2000). Reduced membrane EFA in schizophrenia Abnormal membrane GPL EFA metabolism has been suggested to contribute to the aetiopathophysiology of schizophrenia. A recent review of 15 published studies confirmed a depletion of bioactive lipids in cell membranes of patients with schizophrenia (Fenton et al., 2000). The most consistent findings were reductions in AA and its precursors, and these were independent of drug treatment (Yao et al., 1996). Reductions in AA and its precursors have also been found in post mortem brains of patients with schizophrenia, relative to normal control brains [Yao et al., 2000]. Yao and van Kammen (1996) suggested that defective uptake of AA into membrane GPL was a possible aetiopathological mechanism in schizophrenia, whereas Peet et al. (1996), who reported an additional increase of EFA peroxidation products, suggested there was increased breakdown of membrane GPL. Khan et al. (2002) reported on erythrocyte membrane EFA levels and levels of plasma lipid peroxides, products of damaged EFAs, in drug-naive patients within +/-4.5 days of onset of psychosis. The levels of EFAs, particularly AA and docosahexaenoic acid (DHA) were significantly lower in drug-naive patients at the onset of psychosis compared to matched normal controls. These lower EFA levels were associated with significantly higher levels of lipid peroxides in patients. The levels of AA and DHA were also lower and lipid peroxides higher in chronic medicated patients than normal controls. Interestingly in context with this proposal, EFA levels were higher in chronic medicated patients than drug-naive first-episode patients. Khan et al. concluded that these findings could indicate that lower membrane AA and DHA most likely predate the illness and probably contribute to the onset of illness. The lipid peroxidation data suggest that possible increased oxidative stress may be one of the mechanisms of reduced membrane EFAs. The findings also imply that supplementation of EFAs and/or antioxidants might provide effective treatments for early psychosis. This view is supported by Horrobin et al. (2002) who showed that increase in red cell AA levels resulted from treatment with the optimal levels of EPA and that, clinical improvement was highly significantly positively correlated with rises in red cell membrane AA in individuals with schizophrenia. Treatment studies in schizophrenia Three randomized controlled treatment studies conducted over 12 weeks found 2g/day EPA significantly more effective than placebo in reducing psychopathological symptoms in individuals with schizophrenia (Peet et al., 2001; Emsley et al., 2002). Symptom improvements in those studies were both, clinically relevant and statistically significant. A dose-ranging exploratory study of the effects of EPA in individuals with schizophrenia who experienced persistent symptoms found 2 g EPA/day significantly more effective in reducing symptom scores on psychiatric rating scales than 1g and 4g EPA/day (Peet et al., 2002). On the other hand, Fenton et al. (2002) investigated augmentation of neuroleptics with 3 g/day of EPA on symptoms and cognition in patients with schizophrenia or schizoaffective disorder and reported a negative finding. The patients in Fenton et al.s' study had, however, been ill for two decades and had substantial symptoms, despite treatment with newer neuroleptics, including clozapine. The patients described as benefiting from EPA in the other studies were younger and had a shorter duration of illness. It must be emphasized that in all EPA treatment studies, no treatment-related side effects or adverse biochemical or haematological effects have been observed. EPA proved safe to administer to schizophrenic patients as an adjunct therapy. EPA did not cause side effects other than mild gastrointestinal symptoms by itself, nor did it enhance the side effects of existing drugs. Patients found EPA highly tolerable. The proportion of patients who completed 12 weeks (89%) compares favourably with mean withdrawal rates of 54% in the novel neuroleptic groups and 67% in the placebo groups in trials in the FDA database (Peet et al., 2002). Acceptance of a substance which is normally found in the human body without significant side effects, with a potency potentially similar to the antipsychotic drugs in the early phase of psychotic disorders could contribute to reduce the duration of untreated psychosis and to increase compliance.
- Study design We will use a prospective, randomized, double-blind, placebo-controlled, single-centre study design. Eighty one individuals aged 13-25 will be randomly assigned in two treatment conditions at the University Clinic for Child and Adolescent Neuropsychiatry, Vienna, Austria. Randomization codes will be generated and stored off site. The treatment groups will receive 1.2 gramm per day EPA/DHA or placebo for 12 weeks. Follow-up assessments will be conducted at 1,2,3,4,8,12,26,and 52 weeks. All patients will receive standard treatment, which includes management by a psychiatrist or resident psychiatrist and non-neuroleptic pharmacotherapy as clinically indicated.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: Omega 3 fatty acids |
| B | Placebo comparator | Drug: Omega 3 fatty acidsCoconut oil |
Who may qualify
- Ages
- 13 to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- /written informed consent (for individuals under 18 written informed consent of at least one of the parents is required),
- /age between 13 and 25 years,
- /ARMS as classified by the PACE criteria (Yung et al., 1998)
- PACE criteria for ARMS include one or more of following characteristics which must have occurred within the last 12 months:
- Frank psychotic symptoms < 1 week (Transient psychosis group)
Key exclusion criteria (13 listed)
- /Acute suicidal behaviour, aggressive behaviour (PANSS hostility, suicidality = 7),
- /Drug abuse that contributed decisively to the presentation of the index episode, (dependency on morphine, cocaine, amphetamine, but not THC),
- /Alcohol abuse if considered as major problem,
- /Epilepsy,
- /Mental Retardation (IQ<80),
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Omega 3 fatty acidsThe active treatment is a supplement of yellow gelatin 0.5 g fish oil capsules. The daily dose of 4 (2x2) capsules provides 700 mg of eicosapentaenoic acid and 500 mg of docosahexaenoic acid, and 10 mg of Vitamin E. Placebo treatment comprises coconut oil capsules, carefully matched with the active treatment with respect to both appearance and flavor, also containing 10 mg Vitamin E, and 10 mg of fish oil to mimic taste. Coconut oil was chosen as placebo because it does not contain polyunsaturated fatty acids and has no impact on n-3 fatty acid metabolism. The intervention period is 12 weeks. | Drug | A, B |
Primary outcome
Transition to PANSS defined first-episode psychosis
Time frame: Baseline, 1, 2, 3, 4, 8, 12 weeks, 6, and 12 months
5 secondary outcomes
PANSS positive, negative, and global subscales
Time frame: Baseline, 1, 2, 3, 4, 8, 12 weeks, 6, and 12 months
MADRS
Time frame: Baseline, 1, 2, 3, 4, 8, 12 weeks, 6, and 12 months
GAF
Time frame: Baseline, 1, 2, 3, 4, 8, 12 weeks, 6, and 12 months
UKU
Time frame: Baseline, 1, 2, 3, 4, 8, 12 weeks
Lipid metabolism in peripheral tissue pre/post treatment
Time frame: Baseline, 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2007.
- BackgroundBerger GE, Proffitt TM, McConchie M, et al. Ethyl-Eicosapentaenoic acid in first episode psychosis: A randomized, placebo-controlled trial. Journal of Clinical Psychiatry 2007; in press Berger GE, Wood SJ, Wellard RM, et al. In vivo brain effects of ethyl-eicosapentaenoic acid in early psychosis. A 1H-MRS study. Neuropsychopharmacology 2007;in press.
- Derived from this study: PubMed 28126360Smesny S, Milleit B, Schaefer MR, Hesse J, Schlogelhofer M, Langbein K, Hipler UC, Berger M, Cotter DR, Sauer H, McGorry PD, Amminger GP. Effects of omega-3 PUFA on immune markers in adolescent individuals at ultra-high risk for psychosis - Results of the randomized controlled Vienna omega-3 study. Schizophr Res. 2017 Oct;188:110-117. doi: 10.1016/j.schres.2017.01.026. Epub 2017 Jan 23.
- Derived from this study: PubMed 27650124Focking M, Dicker P, Lopez LM, Cannon M, Schafer MR, McGorry PD, Smesny S, Cotter DR, Amminger GP. Differential expression of the inflammation marker IL12p40 in the at-risk mental state for psychosis: a predictor of transition to psychotic disorder? BMC Psychiatry. 2016 Sep 20;16(1):326. doi: 10.1186/s12888-016-1039-7.
- Derived from this study: PubMed 23870722Amminger GP, Chanen AM, Ohmann S, Klier CM, Mossaheb N, Bechdolf A, Nelson B, Thompson A, McGorry PD, Yung AR, Schafer MR. Omega-3 fatty acid supplementation in adolescents with borderline personality disorder and ultra-high risk criteria for psychosis: a post hoc subgroup analysis of a double-blind, randomized controlled trial. Can J Psychiatry. 2013 Jul;58(7):402-8. doi: 10.1177/070674371305800705.
- Derived from this study: PubMed 20124114Amminger GP, Schafer MR, Papageorgiou K, Klier CM, Cotton SM, Harrigan SM, Mackinnon A, McGorry PD, Berger GE. Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Arch Gen Psychiatry. 2010 Feb;67(2):146-54. doi: 10.1001/archgenpsychiatry.2009.192.
- The Stanley Medical Research InstituteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
G Paul Amminger, MD principal investigator
Medical University of Vienna
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Omega 3 fatty acids in people with Schizophrenia and Prodrome, run by Medical University of Vienna at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Dec 2007. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Transition to PANSS defined first-episode psychosis (time frame: Baseline, 1, 2, 3, 4, 8, 12 weeks, 6, and 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00396643, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Dec 2007.