Treatment of Schizophrenia With an Omega-3 Fatty Acid (EPA) and Antioxidants

Phase 2

Completed

• Conditions: Schizophrenia; Schizophreniform Disorders; Schizoaffective Disorder; Psychotic Disorders
• Interventions: Drug: Ethyl-eicosapentaenoic acid (EPA); Drug: Vitamins E + C; Other: Vitamins E+C (placebo); Other: Etyl EPA (placebo)

• Registration Number: NCT00419146
• Lead Sponsor: University Hospital, Aker

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).

Study Timeline

• Study Start: 2001-09
• Primary Completion: 2004-04
• Study Completion: 2004-04
• Study First Submitted: 2007-01-05
• Study First Submitted QC: 2007-01-05
• Study First Posted: 2007-01-08
• Status Verified: 2010-08
• Last Update Submitted: 2011-01-03
• Last Update Posted: 2011-01-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 99

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Ethyl EPA (active) and Vitamins E + C (active)	Ethyl-eicosapentaenoic acid (EPA)	-
Ethyl EPA (active) and Vitamins E + C (active)	Vitamins E + C	-
Ethyl EPA (active) and Vitamins E+C (placebo)	Ethyl-eicosapentaenoic acid (EPA)	-
Ethyl EPA (active) and Vitamins E+C (placebo)	Vitamins E+C (placebo)	-
Ethyl EPA (placebo) and Vitamins E+C (active)	Vitamins E + C	-
Ethyl EPA (placebo) and Vitamins E+C (active)	Etyl EPA (placebo)	-
Ethyl EPA (placebo) and Vitamins E+C (placebo)	Vitamins E+C (placebo)	-

Primary Outcome Measures

Name	Time	Method
Positive and Negative Syndrome Scale (PANSS)- Total	Baseline - 8 weeks - 16 weeks

Secondary Outcome Measures

Name	Time	Method
Glucose	Weeks 0, 16	Serum - fasting
Cholesterol	Weeks 0, 16	Serum - fasting
Triglycerides	Weeks 0, 16	Serum - fasting
PANSS Subscales Negative, Positive, General Psychopathology	Weeks 0, 8, 16
GLOBAL ASSESSMENT OF FUNCTIONING- Split Version (S-GAF)	Weeks 0, 8, 16	(S-GAF)Symptom Scale (S-GAF)Function Scale
WONCA-COOP FUNCTIONAL HEALTH ASSESSMENT CHARTS	Weeks 0, 8, 16	5 scales
NIACIN SKIN FLUSH TEST	Weeks 0, 8, 16	2 concentrations of niacin
THE UKU SIDE EFFECT RATING SCALE (USERS)	Weeks 0,4,8,12,16	1. Sum of scores; 2. Patients with side effects
SERIOUS ADVERSE EVENTS	Weeks 0,4,8,12,16
CONCOMITANT ANTIPSYCHOTIC MEDICATION	Weeks 0,4,8,12,16	Defined Daily Doses (ATC/WHO)
Kimura Recurring Recognition Figures Test	Weeks 0, 16	A sub-sample of patients. For logistic reasons, only some study sites could participate.
Hopkins Verbal Learning Test.	Weeks 0, 16	A sub-sample of patients. For logistic reasons, only some study sites could participate.
Continuous Performance Test	Weeks 0, 16	A sub-sample of patients. For logistic reasons, only some study sites could participate.
Hopkins Verbal Learning Test	Weeks 0, 16	A sub-sample of patients. For logistic reasons, only some study sites could participate.
Paced Auditory Serial Addition Test	Weeks 0, 16	A sub-sample of patients. For logistic reasons, only some study sites could participate.
Stroop Test	Weeks 0, 16	A sub-sample of patients. For logistic reasons, only some study sites could participate.
Digit Span	Weeks 0, 16	A sub-sample of patients. For logistic reasons, only some study sites could participate.
The Letter - Number Task	Weeks 0,16	A sub-sample of patients. For logistic reasons, only some study sites could participate.
Semantic and Category Fluency	Weeks 0, 16	A sub-sample of patients. For logistic reasons, only some study sites could participate.
Body Mass Index	Weeks 0, 16
Blood pressure - systolic, diastolic	Weeks 0, 16
Heart rate	Weeks 0, 16
Albumin	Weeks 0, 16	Serum
Urate	Weeks 0, 16	Serum
Fatty acids in red blood cells	Weeks 0, 16	The concentrations of long-chain (C14-18) and very long-chain (C20-24)fatty acids in erythrocytes were measured. Fasting condition.; We selected DGLA, AA, EPA, DHA, total omega-3 Polyunsaturated Fatty Acids (PUFA), total omega-6 PUFA, PUFA and LCPUFA (long-chain PUFA) as outcome measures.
Alpha-tocopherol adjusted for [triglycerides]+[cholesterol].	Weeks 0, 16	Serum
Total antioxidant status	Weeks 0, 16	Serum
Malondialdehyde	Weeks 0, 16	Also called "TBARS". Serum
F2-isoprostane (8-epiPGF2-alpha)	Weeks 0, 16	Serum
Cytosolic PLA2 group IV in red blood cells(ELISA method)		Omitted from stastical analyses because of problems with the pre-analytic procedure (treatment the of blood)
Gene expression of mRNA for Phospholipase A2 (PLA2) groups IVa and VIa in monocytes.	Weeks 0, 16	Whole blood
Mean Corpuscular Haemoglobin Concentration (MCHC)	Weeks 0, 16	Whole blood
Mean Corpuscular Volume (MCV)	Weeks 0, 16	Whole blood
C- Reactive Protein (CRP)	Weeks 0, 16	Plasma
Haemoglobin	Weeks 0, 16	Whole blood
Leukocytes	Weeks 0, 16	Whole blood
Calcium	Weeks 0, 16	Serum
Sodium	Weeks 0, 16	Serum
Potassium	Weeks 0, 16	Serum
Ferritin	Weeks 0,16	Serum
Free thyroxin (T4)	Weeks 0, 16	Serum
Thyroid Stimulating Hormone (TSH)	Weeks 0, 16	Serum

Trial Locations

Locations (1)

Aker University Hospital; 🇳🇴 Oslo, Norway