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

This study has been completed.
Sponsor:
Collaborators:
Diakonhjemmet Hospital
Stanley Medical Research Institute
Laxdale Ltd
Scandinavian Society for Psychopharmacology
Shipowner Emil Stray's legacy
Johanne and Einar Eilertsen's research fund
AstraZeneca
Solveig and Johan P. Sommer's foundation
Josef and Haldis Andresen's legacy
University of Oslo
Norwegian University of Science and Technology
Information provided by:
Oslo University Hospital
ClinicalTrials.gov Identifier:
NCT00419146
First received: January 5, 2007
Last updated: January 3, 2011
Last verified: August 2010
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Schizophreniform Disorders
Schizoaffective Disorder
Psychotic Disorders
Drug: Ethyl-eicosapentaenoic acid (EPA)
Drug: Vitamins E + C
Other: Etyl EPA (placebo)
Other: Vitamins E+C (placebo)
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicentre, Placebo-controlled Trial of Eicosapentaenoic Acid (EPA) and Antioxidant Supplementation in the Treatment of Schizophrenia and Related Disorders

Resource links provided by NLM:


Further study details as provided by Oslo University Hospital:

Primary Outcome Measures:
  • Positive and Negative Syndrome Scale (PANSS)- Total [ Time Frame: Baseline - 8 weeks - 16 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • PANSS Subscales Negative, Positive, General Psychopathology [ Time Frame: Weeks 0, 8, 16 ] [ Designated as safety issue: No ]
  • GLOBAL ASSESSMENT OF FUNCTIONING- Split Version (S-GAF) [ Time Frame: Weeks 0, 8, 16 ] [ Designated as safety issue: No ]
    (S-GAF)Symptom Scale (S-GAF)Function Scale

  • WONCA-COOP FUNCTIONAL HEALTH ASSESSMENT CHARTS [ Time Frame: Weeks 0, 8, 16 ] [ Designated as safety issue: No ]
    5 scales

  • NIACIN SKIN FLUSH TEST [ Time Frame: Weeks 0, 8, 16 ] [ Designated as safety issue: No ]
    2 concentrations of niacin

  • THE UKU SIDE EFFECT RATING SCALE (USERS) [ Time Frame: Weeks 0,4,8,12,16 ] [ Designated as safety issue: Yes ]
    1. Sum of scores
    2. Patients with side effects

  • SERIOUS ADVERSE EVENTS [ Time Frame: Weeks 0,4,8,12,16 ] [ Designated as safety issue: Yes ]
  • CONCOMITANT ANTIPSYCHOTIC MEDICATION [ Time Frame: Weeks 0,4,8,12,16 ] [ Designated as safety issue: No ]
    Defined Daily Doses (ATC/WHO)

  • Kimura Recurring Recognition Figures Test [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: No ]
    A sub-sample of patients. For logistic reasons, only some study sites could participate.

  • Hopkins Verbal Learning Test. [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: No ]
    A sub-sample of patients. For logistic reasons, only some study sites could participate.

  • Continuous Performance Test [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: No ]
    A sub-sample of patients. For logistic reasons, only some study sites could participate.

  • Hopkins Verbal Learning Test [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: No ]
    A sub-sample of patients. For logistic reasons, only some study sites could participate.

  • Paced Auditory Serial Addition Test [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: No ]
    A sub-sample of patients. For logistic reasons, only some study sites could participate.

  • Stroop Test [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: No ]
    A sub-sample of patients. For logistic reasons, only some study sites could participate.

  • Digit Span [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: No ]
    A sub-sample of patients. For logistic reasons, only some study sites could participate.

  • The Letter - Number Task [ Time Frame: Weeks 0,16 ] [ Designated as safety issue: No ]
    A sub-sample of patients. For logistic reasons, only some study sites could participate.

  • Semantic and Category Fluency [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: No ]
    A sub-sample of patients. For logistic reasons, only some study sites could participate.

  • Body Mass Index [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: Yes ]
  • Blood pressure - systolic, diastolic [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: Yes ]
  • Heart rate [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: Yes ]
  • Albumin [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: Yes ]
    Serum

  • Urate [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: Yes ]
    Serum

  • Glucose [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: Yes ]
    Serum - fasting

  • Cholesterol [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: Yes ]
    Serum - fasting

  • Triglycerides [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: Yes ]
    Serum - fasting

  • Fatty acids in red blood cells [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: No ]

    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]. [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: No ]
    Serum

  • Total antioxidant status [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: No ]
    Serum

  • Malondialdehyde [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: Yes ]
    Also called "TBARS". Serum

  • F2-isoprostane (8-epiPGF2-alpha) [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: No ]
    Whole blood

  • Mean Corpuscular Haemoglobin Concentration (MCHC) [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: Yes ]
    Whole blood

  • Mean Corpuscular Volume (MCV) [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: Yes ]
    Whole blood

  • C- Reactive Protein (CRP) [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: Yes ]
    Plasma

  • Haemoglobin [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: Yes ]
    Whole blood

  • Leukocytes [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: Yes ]
    Whole blood

  • Calcium [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: Yes ]
    Serum

  • Sodium [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: Yes ]
    Serum

  • Potassium [ Time Frame: Weeks 0, 16 ]
    Serum

  • Ferritin [ Time Frame: Weeks 0,16 ] [ Designated as safety issue: Yes ]
    Serum

  • Free thyroxin (T4) [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: Yes ]
    Serum

  • Thyroid Stimulating Hormone (TSH) [ Time Frame: Weeks 0, 16 ] [ Designated as safety issue: Yes ]
    Serum


Enrollment: 99
Study Start Date: September 2001
Study Completion Date: April 2004
Primary Completion Date: April 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ethyl EPA (active) and Vitamins E + C (active) Drug: Ethyl-eicosapentaenoic acid (EPA)
Capsules, 2 g per day for 16 weeks
Other Name: Provided by Laxdale Ltd., Scotland, UK
Drug: Vitamins E + C
RRR-alpha-tocopherol 392 mg + slow-release ascorbic acid 1000 mg per day, for 16 weeks
Other Name: CellaVie (Ferrosan AS, Denmark)
Experimental: Ethyl EPA (active) and Vitamins E+C (placebo) Drug: Ethyl-eicosapentaenoic acid (EPA)
Capsules, 2 g per day for 16 weeks
Other Name: Provided by Laxdale Ltd., Scotland, UK
Other: Vitamins E+C (placebo)
Tablets containing dicalciumphosphate
Other Name: Placebo CellaVie, provided by Ferrosan AS, Denmark
Experimental: Ethyl EPA (placebo) and Vitamins E+C (active) Drug: Vitamins E + C
RRR-alpha-tocopherol 392 mg + slow-release ascorbic acid 1000 mg per day, for 16 weeks
Other Name: CellaVie (Ferrosan AS, Denmark)
Other: Etyl EPA (placebo)
Paraffin oil. Capsules, each 0.5 g.
Other Name: Placebo EPA
Placebo Comparator: Ethyl EPA (placebo) and Vitamins E+C (placebo) Other: Vitamins E+C (placebo)
Tablets containing dicalciumphosphate
Other Name: Placebo CellaVie, provided by Ferrosan AS, Denmark

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

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00419146

Locations
Norway
Aker University Hospital
Oslo, Norway, 0320
Sponsors and Collaborators
University Hospital, Aker
Diakonhjemmet Hospital
Stanley Medical Research Institute
Laxdale Ltd
Scandinavian Society for Psychopharmacology
Shipowner Emil Stray's legacy
Johanne and Einar Eilertsen's research fund
AstraZeneca
Solveig and Johan P. Sommer's foundation
Josef and Haldis Andresen's legacy
University of Oslo
Norwegian University of Science and Technology
Investigators
Study Director: Håvard Bentsen, MD PhD Aker University Hospital (-2004), Diakonhjemmet Hospital (2004-)
Study Chair: Odd Lingjærde, MD PhD University Hospital, Aker
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00419146     History of Changes
Other Study ID Numbers: LA.01.07.0001, 01T-106 (Stanley M.R.I.,USA)
Study First Received: January 5, 2007
Last Updated: January 3, 2011
Health Authority: Norway: Norwegian Medicines Agency

Keywords provided by Oslo University Hospital:
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

Additional relevant MeSH terms:
Psychotic Disorders
Schizophrenia
Mental Disorders
Disease
Schizophrenia and Disorders with Psychotic Features
Pathologic Processes
Vitamins
Vitamin E
Alpha-Tocopherol
Tocopherols
Tocotrienols
Antioxidants
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Molecular Mechanisms of Pharmacological Action
Protective Agents

ClinicalTrials.gov processed this record on September 16, 2014