Primary objective of this randomised controlled trial is to compare transition rates to psychosis between individuals who are at UHR for developing psychosis and randomised to treatment with omega-3 fatty acids to those randomised to placebo, as…
ID
Source
Brief title
Condition
- Schizophrenia and other psychotic disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Transition to psychosis will be defined using the CAARMS criteria or when a
subject exceeds the maximally allowed dose of antipsychotics during the study
(i.e. equivalent of a total haloperidol use of 10 mg within two months).
Secondary outcome
Symptomatology will be examined using semi-structured interviews and
questionnaires including the CAARMS, Positive and Negative Syndrome Scale
(PANSS), Global Assessment of Functioning scale (GAF), Clinical Global
Impression Scale (CGI) and Beck*s Depression Inventory (BDI). Cognition will be
assessed using a computerised battery of neuropsychological tests that capture
key deficits associated with psychosis, such as memory, social perception and
reasoning. Blood samples will be drawn to assess levels of bioactive lipids,
(epi)genetic markers and immune parameters. Finally, brain structure and
function are measured in three MRI sessions, consisting of structural MRI,
resting state functional MRI, Diffusion Tensor Imaging (DTI), functional MRI
during reward processing and magnetic resonance spectroscopy (MRS).
Background summary
Psychosis is a chronic and severe mental disorder, usually preceded by a
prodromal phase of attenuated psychotic symptoms and decline in function.
Intervention during this prodromal state could prevent transition to psychosis,
and is therefore of high significance. A recent randomised controlled trial
with individuals at ultra-high risk (UHR) for psychosis showed a significantly
lower transition rate to psychosis and reduced psychotic symptoms in those
subjects who were treated daily with omega-3 fatty acids compared to placebo.
Here we further evaluate the potential of omega-3 fatty acids in the prevention
of psychosis.
Study objective
Primary objective of this randomised controlled trial is to compare transition
rates to psychosis between individuals who are at UHR for developing psychosis
and randomised to treatment with omega-3 fatty acids to those randomised to
placebo, as determined through the Comprehensive Assessment of At-Risk Mental
State (CAARMS) or when a subject exceeds the maximally allowed dose of
antipsychotics during the study (i.e. equivalent of a total haloperidol use of
10 mg within two months). Secondary objectives include a comparison between the
two treatment arms with regard to discontinuation rate, tolerability,
symptomatology, psychosocial and cognitive function, quality of life, blood
levels of bioactive lipids, (epi)genetic markers and immune parameters. Third,
the ability of both MRI and blood parameters to serve as potential biomarkers
that may predict clinical response of UHR subjects will be elucidated. Finally,
both cross-sectional and longitudinal comparisons of study parameters will be
conducted between UHR subjects and healthy controls.
Study design
A European, multicentre, randomised, double-blind, placebo-controlled clinical
trial.
Intervention
Omega-3 fatty acids versus placebo.
Study burden and risks
This study includes eight site visits. The first two visits occur before
treatment initiation, and consist of screening for in- and exclusion criteria,
a diagnostic interview, and baseline examination of symptomatology,
psychosocial and cognitive function, quality of life and drug use. Four blood
samples are drawn to perform standard clinical laboratory tests and to assess
levels of bioactive lipids, (epi)genetic markers and immune parameters.
Subjects will undergo a baseline MRI session of maximum ninety minutes. Both
blood sampling and MRI are safe procedures, and standard procedures will be
followed to minimise risks. Subsequent visits take place at 1 month, 3 months,
6 months, 1 year, 1.5 years and 2 years after inclusion in the study. During
these visits, interviews and questionnaires performed at baseline will be
repeated. At visits 5 and 8, three blood samples will be drawn to assess levels
of bioactive lipids, (epi)genetic markers and immune parameters. Transition to
psychosis will be assessed at all time points using the CAARMS criteria. UHR
individuals younger than 18 years of age will be included in this study, as
attenuated symptoms of psychosis typically emerge in adolescence. However,
participation in this randomised controlled trial may be of therapeutic benefit
to UHR subjects since treatment with omega-3 fatty acids has been associated
with prevention of the transition to psychosis. Omega-3 fatty acids are food
supplements with important physical health benefits and are minimally
associated with adverse effects.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
- 13-20 years old (inclusive)
- Written informed consent of the subject. For individuals below the age of
legal capacity 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
•Intake of an antipsychotic or mood-stabilising agent in the two weeks prior to
study inclusion, except for situations as described in section 5.2 of the
protocol
•Intake of an antipsychotic agent equivalent to a total haloperidol use of >50
mg in the six months prior to study inclusion, except for situations as
described in section 5.2 of the protocol
•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
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-003503-39-NL |
| ClinicalTrials.gov | NCT02597439 |
| CCMO | NL55399.041.15 |