This study will assess the effects of poly-unsaturated fatty acids on working memory (measured using an n-back test) in healthy volunteers, in subjects who are at high risk for developing a psychotic disorder and in patients with first-episode schizophrenia. MedDRA version: 20.0 Level: HLGT Classification code 10039628 Term: Schizophrenia and other psychotic disorders System Organ Class: 10037175 - Psychiatric disorders
Conditions
Interventions
Trade Name: EPAX 6000 TG 1000 mg Kapseln
Product Name: EPAX 6000 TG 1000 mg Kapseln
Pharmaceutical Form: Capsule
INN or Proposed INN: DOCOSAHEXAENOIC ACID
CAS Number: 6217-54-5
Concentration unit: mg
Sponsors
Medizinische Universität Wien
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All subjects • age 18-65 • good general health • absence of relevant abnormalities in laboratory screening, ECG or vital signs • no regular use of drugs of abuse or alcohol based on history and urine drug screen. Healthy subjects • Absence of psychiatric disorders according to M.I.N.I. ARMS subjects • CAARMS above ARMS threshold Patients with schizophrenia • diagnosis of SCZ or other non-affective psychotic disorder according to DSM-5 • minimum Positive and Negative Syndrome Scale (PANSS) total score of 55 (> 3 on at least two or >4 on one psychosis item • ability to give informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 66 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: All subjects • severe or unstable medical or neurologic disorders or clinically significant abnormality on screening laboratory studies • clinically relevant abnormalities in the electro-cardiogram (ECG) • history of myocardial infarction or angina pectoris, arterial hypertension or paroxysmal hypertensive states • established diagnosis of advanced arteriosclerosis or hyperthyroidism • current substance use disorder (except nicotine) • lifetime use of stimulants exceeding 5 or more exposures • pregnancy or breast feeding • known hypersensitivity to sympathomimetics • history of severe head trauma • positive urine drug screen • presence of MRI exclusion criteria • if participation in this study would exceed annual radiation dose limits (30mSv) • known allergy to any ingredients of the PUFA or placebo capsules • Patients with schizophrenia • previous oral antipsychotic treatment for more than 2 weeks, or antipsychotics within two weeks prior to PET scan; previous treatment with antipsychotic depot preparation. • ARMS subjects • psychotic disorder according to DSM-5 (CAARMS above psychosis threshold)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To study the effects of dietary supplementation with poly-unsaturated fatty acids(PUFAs) and of amphetamine-induced dopamine-release on dopamine-dependent, working-memory related brain networks. To develop a [11C]-(+)-PHNO positron-emission tomography (PET) paradigm for the 3T Siemens mMRBiograph system for studying amphetamine-induced dopamine release in a single scanning session. To develop an in-vitro model of altered dopamine function in schizophrenia by transorming fibroblasts derived from study participants viy skin punch biopsy into dopaminergic neuron-like cells. To study the impact of phospholipase-2 (PLA2) stimulation by melittin and PUFAs on the dopamine transporter in HEK 293 cells and later in fibroblast-derived neuron-like cells; initiation of molecular dynamics (MD) simulations on the impact of dopamine transporter conformations.;Secondary Objective: To relate the magnitude of amphetamine-induced dopamine-release measured with [11C]-(+)-PHNO PET on specific functional brain networks (for example default-mode network) using functional magnetic resonance imaging (fMRI) and connectivity analyses.;Primary end point(s): 1) To measure an increased amphetamine-induced reduction in binding of the dopamine D2/3 agonist radioligand [11C]-(+)-PHNO in patients with schizophrenia and part of the at risk mental state (ARMS) collective as compared to healthy control subjects. 2) To measure a significant amphetamine-induced reduction in working memory performance assessed using an n-back paradigm in subjects with presumed high baseline dopamine activity (patients with schizophrenia and part of the ARMS collective). 3) To measure a normalization of amphetamine-induced reductions in [11C]-(+)-PHNO binding in ARMS subjects with increased baseline response after PUFA intakeas compared to placebo.;Timepoint(s) of evaluation of this end point: 1) and 2) at baseline (i.e. before PUFA or placebo intake) 3) after intake of PUFA (EPAX 6000) capsules for 8-12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) To measure alterations in dopamine-related brain networks (at rest and while performing an n-back test) in patients with schizophrenia or ARMS as compared to healthy control subjects using functional magnetic resonance imaging 2) To relate amphetamine-induced changes in these networks to amphetamine-induced dopamine release as measured by reductions in [11C]-(+)-PHNO binding 3) To image changes in the response of dopamine-related brain networks to amphetamine after PUFA (EPAX 6000) supplementation in healthy and ARMS subjects ;Timepoint(s) of evaluation of this end point: 1) and 2) at baseline (i.e. before PUFA or placebo intake) 3) after intake of PUFA (EPAX 6000) capsules for 8-12 weeks and after intake of placebo for 8-12 weeks | — |
Countries
Austria
Contacts
Public ContactDept. of Psychiatry & Psychotherapy
Medizinische Universität Wien
Outcome results
None listed