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

Schizophrenia Clinical Trial

Official title:

A Multicentre, Placebo-controlled Trial of Eicosapentaenoic Acid (EPA) and Antioxidant Supplementation in the Treatment of Schizophrenia and Related Disorders

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00419146
• Other study ID #: LA.01.07.0001
• Secondary ID: 01T-106 (Stanley
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: January 5, 2007
• Last updated: January 3, 2011
• Start date: September 2001
• Est. completion date: April 2004

Study information

• Verified date: August 2010
• Source: Oslo University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Norway: Norwegian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 99
• Est. completion date: April 2004
• Est. primary completion date: April 2004
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 40 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Disease
• Mental Disorders
• Psychotic Disorders
• Schizoaffective Disorder
• Schizophrenia
• Schizophreniform Disorders

Intervention

Drug:
• Ethyl-eicosapentaenoic acid (EPA)
Capsules, 2 g per day for 16 weeks
• Vitamins E + C
RRR-alpha-tocopherol 392 mg + slow-release ascorbic acid 1000 mg per day, for 16 weeks

Other:
• Etyl EPA (placebo)
Paraffin oil. Capsules, each 0.5 g.
• Vitamins E+C (placebo)
Tablets containing dicalciumphosphate

Locations

Country	Name	City	State
Norway	Aker University Hospital	Oslo

Sponsors (12)

Lead Sponsor	Collaborator
University Hospital, Aker	AstraZeneca, Diakonhjemmet Hospital, Johanne and Einar Eilertsen's research fund, Josef and Haldis Andresen's legacy, Laxdale Ltd, Norwegian University of Science and Technology, Scandinavian Society for Psychopharmacology, Shipowner Emil Stray's legacy, Solveig and Johan P. Sommer's foundation, Stanley Medical Research Institute, University of Oslo

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Positive and Negative Syndrome Scale (PANSS)- Total		Baseline - 8 weeks - 16 weeks	No
Secondary	PANSS Subscales Negative, Positive, General Psychopathology		Weeks 0, 8, 16	No
Secondary	GLOBAL ASSESSMENT OF FUNCTIONING- Split Version (S-GAF)	(S-GAF)Symptom Scale (S-GAF)Function Scale	Weeks 0, 8, 16	No
Secondary	WONCA-COOP FUNCTIONAL HEALTH ASSESSMENT CHARTS	5 scales	Weeks 0, 8, 16	No
Secondary	NIACIN SKIN FLUSH TEST	2 concentrations of niacin	Weeks 0, 8, 16	No
Secondary	THE UKU SIDE EFFECT RATING SCALE (USERS)	Sum of scores; Patients with side effects	Weeks 0,4,8,12,16	Yes
Secondary	SERIOUS ADVERSE EVENTS		Weeks 0,4,8,12,16	Yes
Secondary	CONCOMITANT ANTIPSYCHOTIC MEDICATION	Defined Daily Doses (ATC/WHO)	Weeks 0,4,8,12,16	No
Secondary	Kimura Recurring Recognition Figures Test	A sub-sample of patients. For logistic reasons, only some study sites could participate.	Weeks 0, 16	No
Secondary	Hopkins Verbal Learning Test.	A sub-sample of patients. For logistic reasons, only some study sites could participate.	Weeks 0, 16	No
Secondary	Continuous Performance Test	A sub-sample of patients. For logistic reasons, only some study sites could participate.	Weeks 0, 16	No
Secondary	Hopkins Verbal Learning Test	A sub-sample of patients. For logistic reasons, only some study sites could participate.	Weeks 0, 16	No
Secondary	Paced Auditory Serial Addition Test	A sub-sample of patients. For logistic reasons, only some study sites could participate.	Weeks 0, 16	No
Secondary	Stroop Test	A sub-sample of patients. For logistic reasons, only some study sites could participate.	Weeks 0, 16	No
Secondary	Digit Span	A sub-sample of patients. For logistic reasons, only some study sites could participate.	Weeks 0, 16	No
Secondary	The Letter - Number Task	A sub-sample of patients. For logistic reasons, only some study sites could participate.	Weeks 0,16	No
Secondary	Semantic and Category Fluency	A sub-sample of patients. For logistic reasons, only some study sites could participate.	Weeks 0, 16	No
Secondary	Body Mass Index		Weeks 0, 16	Yes
Secondary	Blood pressure - systolic, diastolic		Weeks 0, 16	Yes
Secondary	Heart rate		Weeks 0, 16	Yes
Secondary	Albumin	Serum	Weeks 0, 16	Yes
Secondary	Urate	Serum	Weeks 0, 16	Yes
Secondary	Glucose	Serum - fasting	Weeks 0, 16	Yes
Secondary	Cholesterol	Serum - fasting	Weeks 0, 16	Yes
Secondary	Triglycerides	Serum - fasting	Weeks 0, 16	Yes
Secondary	Fatty acids in red blood cells	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.	Weeks 0, 16	No
Secondary	Alpha-tocopherol adjusted for [triglycerides]+[cholesterol].	Serum	Weeks 0, 16	No
Secondary	Total antioxidant status	Serum	Weeks 0, 16	No
Secondary	Malondialdehyde	Also called "TBARS". Serum	Weeks 0, 16	Yes
Secondary	F2-isoprostane (8-epiPGF2-alpha)	Serum	Weeks 0, 16	Yes
Secondary	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)
Secondary	Gene expression of mRNA for Phospholipase A2 (PLA2) groups IVa and VIa in monocytes.	Whole blood	Weeks 0, 16	No
Secondary	Mean Corpuscular Haemoglobin Concentration (MCHC)	Whole blood	Weeks 0, 16	Yes
Secondary	Mean Corpuscular Volume (MCV)	Whole blood	Weeks 0, 16	Yes
Secondary	C- Reactive Protein (CRP)	Plasma	Weeks 0, 16	Yes
Secondary	Haemoglobin	Whole blood	Weeks 0, 16	Yes
Secondary	Leukocytes	Whole blood	Weeks 0, 16	Yes
Secondary	Calcium	Serum	Weeks 0, 16	Yes
Secondary	Sodium	Serum	Weeks 0, 16	Yes
Secondary	Potassium	Serum	Weeks 0, 16
Secondary	Ferritin	Serum	Weeks 0,16	Yes
Secondary	Free thyroxin (T4)	Serum	Weeks 0, 16	Yes
Secondary	Thyroid Stimulating Hormone (TSH)	Serum	Weeks 0, 16	Yes