Clinical trial NCT00419146: Treatment of Schizophrenia With an Omega-3 Fatty Acid (EPA) and Antioxidants
Official title: A Multicentre, Placebo-controlled Trial of Eicosapentaenoic Acid (EPA) and Antioxidant Supplementation in the Treatment of Schizophrenia and Related Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Schizophrenia
Schizophreniform Disorders
Schizoaffective Disorder
Psychotic Disorders
Keywords: Schizophrenia
Schizophreniform disorders
Schizoaffective disorder
Psychotic disorders
Randomized Controlled Trials
Longitudinal Studies
Fatty Acids, Omega-3
Eicosapentaenoic Acid
Vitamins
Antioxidants
Ascorbic Acid
Alpha-Tocopherol
Placebos
Antipsychotic Agents
Oxidative Stress
Fatty Acids, Unsaturated
Phospholipases
Niacin
Adverse effects
Delusions
Hallucinations
Neuropsychological Tests
Attention
Memory
Hypertriglyceridemia
Models, Statistical
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: Diakonhjemmet Hospital
name: Stanley Medical Research Institute
name: Laxdale Ltd
name: Scandinavian Society for Psychopharmacology
name: Shipowner Emil Stray's legacy
name: Johanne and Einar Eilertsen's research fund
name: AstraZeneca
name: Solveig and Johan P. Sommer's foundation
name: Josef and Haldis Andresen's legacy
name: University of Oslo
name: Norwegian University of Science and Technology
First posted: 2007-01-08
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is to study the effect of adding the omega-3 fatty acid EPA and/or Vitamins E + C to antipsychotic drugs in younger patients with schizophrenia and related psychoses.

Detailed description: Objective:

Study the effect of adding Ethyl-EPA and/or Vitamins E + C to antipsychotic drugs in younger patients with schizophrenia and related psychoses.

Methods and material:

* Design: Multicentre, randomized, double-blind, placebo-controlled, fixed dose, 2x2 factorial, add-on clinical trial.
* Sample:

  * Patients with schizophrenia, schizoaffective disorder or schizophreniform disorder (DSM-IV); aged 18-40 years; less than 15 years since first psychotic symptoms;admitted to a psychiatric department within the previous 21 days before screening; speaks fluently a Scandinavian language;treated with antipsychotics; written informed consent;no known allergy to trial agents;no substance dependence (DSM-IV);no warfarin currently or anamnestic indicators of impaired haemostasis. Planned: 200 patients. Actually included: 99 intent-to-treat patients.
  * Healthy controls: aged 18-40 years;no mental disorder (DSM-IV). Included: 20 persons.
* Clinical assessments: Positive and Negative Syndrome Scale (PANSS) (main outcome variable). Self-report questionnaire. Adverse effects (UKURS). Neurocognitive assessment battery. Niacin skin flush test. General medical assessment.
* Blood samples: RBC fatty acids, S-α-tocopherol, F2-isoprostane (kits), monocyte mRNA Phospholipase A22 (PLA2) Gr4a and 6a (RT-PCR method), RBC Gr4a PLA2 concentration (ELISA technique), a range of other biochemical tests.
* Experimental treatment over 16 weeks: Ethyl-EPA 2 g/d or Placebo EPA and Vitamin E 364 mg/d + Vitamin C 1000 mg/d or Placebo Antioxidants
* Statistics: Linear Mixed Model for longitudinal analyses of effects; other uni- and multivariate methods (SPSS 12.0 - PASW Statistics 18).

Eligibility criteria: Inclusion Criteria:

* Patients with schizophrenia, schizophreniform disorder or schizoaffective disorder (DSM-IV)
* Admitted to a psychiatric hospital/department within the previous twenty-one days before screening
* Less than fifteen years, in retrospect, since first psychotic symptoms (DSM-IV 295, criteria A,1-4)
* Age 18-40 years
* Speaks fluently a Scandinavian language
* A written informed consent must be obtained before any trial-related activities

Exclusion Criteria:

* A diagnosis of substance dependence (DSM-IV)
* Known allergy to study medication
* Currently taking warfarin or having anamnestic indicators of impaired haemostasis (profuse bleeding, except epistaxis)

Primary outcomes:
measure: Positive and Negative Syndrome Scale (PANSS)- Total
timeFrame: Baseline - 8 weeks - 16 weeks
Secondary outcomes:
measure: PANSS Subscales Negative, Positive, General Psychopathology
timeFrame: Weeks 0, 8, 16
measure: GLOBAL ASSESSMENT OF FUNCTIONING- Split Version (S-GAF)
timeFrame: Weeks 0, 8, 16
measure: WONCA-COOP FUNCTIONAL HEALTH ASSESSMENT CHARTS
timeFrame: Weeks 0, 8, 16
measure: NIACIN SKIN FLUSH TEST
timeFrame: Weeks 0, 8, 16
measure: THE UKU SIDE EFFECT RATING SCALE (USERS)
timeFrame: Weeks 0,4,8,12,16
measure: SERIOUS ADVERSE EVENTS
timeFrame: Weeks 0,4,8,12,16
measure: CONCOMITANT ANTIPSYCHOTIC MEDICATION
timeFrame: Weeks 0,4,8,12,16
measure: Kimura Recurring Recognition Figures Test
timeFrame: Weeks 0, 16
measure: Hopkins Verbal Learning Test.
timeFrame: Weeks 0, 16
measure: Continuous Performance Test
timeFrame: Weeks 0, 16
measure: Hopkins Verbal Learning Test
timeFrame: Weeks 0, 16
measure: Paced Auditory Serial Addition Test
timeFrame: Weeks 0, 16
measure: Stroop Test
timeFrame: Weeks 0, 16
measure: Digit Span
timeFrame: Weeks 0, 16
measure: The Letter - Number Task
timeFrame: Weeks 0,16
measure: Semantic and Category Fluency
timeFrame: Weeks 0, 16
measure: Body Mass Index
timeFrame: Weeks 0, 16
measure: Blood pressure - systolic, diastolic
timeFrame: Weeks 0, 16
measure: Heart rate
timeFrame: Weeks 0, 16
measure: Albumin
timeFrame: Weeks 0, 16
measure: Urate
timeFrame: Weeks 0, 16
measure: Glucose
timeFrame: Weeks 0, 16
measure: Cholesterol
timeFrame: Weeks 0, 16
measure: Triglycerides
timeFrame: Weeks 0, 16
measure: Fatty acids in red blood cells
timeFrame: Weeks 0, 16
measure: Alpha-tocopherol adjusted for [triglycerides]+[cholesterol].
timeFrame: Weeks 0, 16
measure: Total antioxidant status
timeFrame: Weeks 0, 16
measure: Malondialdehyde
timeFrame: Weeks 0, 16
measure: F2-isoprostane (8-epiPGF2-alpha)
timeFrame: Weeks 0, 16
measure: Cytosolic PLA2 group IV in red blood cells(ELISA method)
measure: Gene expression of mRNA for Phospholipase A2 (PLA2) groups IVa and VIa in monocytes.
timeFrame: Weeks 0, 16
measure: Mean Corpuscular Haemoglobin Concentration (MCHC)
timeFrame: Weeks 0, 16
measure: Mean Corpuscular Volume (MCV)
timeFrame: Weeks 0, 16
measure: C- Reactive Protein (CRP)
timeFrame: Weeks 0, 16
measure: Haemoglobin
timeFrame: Weeks 0, 16
measure: Leukocytes
timeFrame: Weeks 0, 16
measure: Calcium
timeFrame: Weeks 0, 16
measure: Sodium
timeFrame: Weeks 0, 16
measure: Potassium
timeFrame: Weeks 0, 16
measure: Ferritin
timeFrame: Weeks 0,16
measure: Free thyroxin (T4)
timeFrame: Weeks 0, 16
measure: Thyroid Stimulating Hormone (TSH)
timeFrame: Weeks 0, 16
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Aker University Hospital
Study officials:
affiliation: Aker University Hospital (-2004), Diakonhjemmet Hospital (2004-)
name: Håvard Bentsen, MD PhD
role: STUDY_DIRECTOR
affiliation: University Hospital, Aker
name: Odd Lingjærde, MD PhD
role: STUDY_CHAIR
References: