ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00419146
Recruitment Status : Completed
First Posted : January 8, 2007
Last Update Posted : January 4, 2011
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

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.

Condition or disease Intervention/treatment 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

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 99 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : September 2001
Actual Primary Completion Date : April 2004
Actual Study Completion Date : April 2004

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
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



Primary Outcome Measures :
  1. Positive and Negative Syndrome Scale (PANSS)- Total [ Time Frame: Baseline - 8 weeks - 16 weeks ]

Secondary Outcome Measures :
  1. PANSS Subscales Negative, Positive, General Psychopathology [ Time Frame: Weeks 0, 8, 16 ]
  2. GLOBAL ASSESSMENT OF FUNCTIONING- Split Version (S-GAF) [ Time Frame: Weeks 0, 8, 16 ]
    (S-GAF)Symptom Scale (S-GAF)Function Scale

  3. WONCA-COOP FUNCTIONAL HEALTH ASSESSMENT CHARTS [ Time Frame: Weeks 0, 8, 16 ]
    5 scales

  4. NIACIN SKIN FLUSH TEST [ Time Frame: Weeks 0, 8, 16 ]
    2 concentrations of niacin

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

  6. SERIOUS ADVERSE EVENTS [ Time Frame: Weeks 0,4,8,12,16 ]
  7. CONCOMITANT ANTIPSYCHOTIC MEDICATION [ Time Frame: Weeks 0,4,8,12,16 ]
    Defined Daily Doses (ATC/WHO)

  8. Kimura Recurring Recognition Figures Test [ Time Frame: Weeks 0, 16 ]
    A sub-sample of patients. For logistic reasons, only some study sites could participate.

  9. Hopkins Verbal Learning Test. [ Time Frame: Weeks 0, 16 ]
    A sub-sample of patients. For logistic reasons, only some study sites could participate.

  10. Continuous Performance Test [ Time Frame: Weeks 0, 16 ]
    A sub-sample of patients. For logistic reasons, only some study sites could participate.

  11. Hopkins Verbal Learning Test [ Time Frame: Weeks 0, 16 ]
    A sub-sample of patients. For logistic reasons, only some study sites could participate.

  12. Paced Auditory Serial Addition Test [ Time Frame: Weeks 0, 16 ]
    A sub-sample of patients. For logistic reasons, only some study sites could participate.

  13. Stroop Test [ Time Frame: Weeks 0, 16 ]
    A sub-sample of patients. For logistic reasons, only some study sites could participate.

  14. Digit Span [ Time Frame: Weeks 0, 16 ]
    A sub-sample of patients. For logistic reasons, only some study sites could participate.

  15. The Letter - Number Task [ Time Frame: Weeks 0,16 ]
    A sub-sample of patients. For logistic reasons, only some study sites could participate.

  16. Semantic and Category Fluency [ Time Frame: Weeks 0, 16 ]
    A sub-sample of patients. For logistic reasons, only some study sites could participate.

  17. Body Mass Index [ Time Frame: Weeks 0, 16 ]
  18. Blood pressure - systolic, diastolic [ Time Frame: Weeks 0, 16 ]
  19. Heart rate [ Time Frame: Weeks 0, 16 ]
  20. Albumin [ Time Frame: Weeks 0, 16 ]
    Serum

  21. Urate [ Time Frame: Weeks 0, 16 ]
    Serum

  22. Glucose [ Time Frame: Weeks 0, 16 ]
    Serum - fasting

  23. Cholesterol [ Time Frame: Weeks 0, 16 ]
    Serum - fasting

  24. Triglycerides [ Time Frame: Weeks 0, 16 ]
    Serum - fasting

  25. Fatty acids in red blood cells [ Time Frame: 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.


  26. Alpha-tocopherol adjusted for [triglycerides]+[cholesterol]. [ Time Frame: Weeks 0, 16 ]
    Serum

  27. Total antioxidant status [ Time Frame: Weeks 0, 16 ]
    Serum

  28. Malondialdehyde [ Time Frame: Weeks 0, 16 ]
    Also called "TBARS". Serum

  29. F2-isoprostane (8-epiPGF2-alpha) [ Time Frame: Weeks 0, 16 ]
    Serum

  30. 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)

  31. Gene expression of mRNA for Phospholipase A2 (PLA2) groups IVa and VIa in monocytes. [ Time Frame: Weeks 0, 16 ]
    Whole blood

  32. Mean Corpuscular Haemoglobin Concentration (MCHC) [ Time Frame: Weeks 0, 16 ]
    Whole blood

  33. Mean Corpuscular Volume (MCV) [ Time Frame: Weeks 0, 16 ]
    Whole blood

  34. C- Reactive Protein (CRP) [ Time Frame: Weeks 0, 16 ]
    Plasma

  35. Haemoglobin [ Time Frame: Weeks 0, 16 ]
    Whole blood

  36. Leukocytes [ Time Frame: Weeks 0, 16 ]
    Whole blood

  37. Calcium [ Time Frame: Weeks 0, 16 ]
    Serum

  38. Sodium [ Time Frame: Weeks 0, 16 ]
    Serum

  39. Potassium [ Time Frame: Weeks 0, 16 ]
    Serum

  40. Ferritin [ Time Frame: Weeks 0,16 ]
    Serum

  41. Free thyroxin (T4) [ Time Frame: Weeks 0, 16 ]
    Serum

  42. Thyroid Stimulating Hormone (TSH) [ Time Frame: Weeks 0, 16 ]
    Serum



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

ClinicalTrials.gov Identifier: NCT00419146     History of Changes
Other Study ID Numbers: LA.01.07.0001
01T-106 (Stanley M.R.I.,USA)
First Posted: January 8, 2007    Key Record Dates
Last Update Posted: January 4, 2011
Last Verified: August 2010

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:
Disease
Schizophrenia
Psychotic Disorders
Mental Disorders
Pathologic Processes
Schizophrenia Spectrum and Other Psychotic Disorders
Vitamins
Vitamin E
Tocopherols
Tocotrienols
alpha-Tocopherol
Ascorbic Acid
Antioxidants
Micronutrients
Growth Substances
Physiological Effects of Drugs
Molecular Mechanisms of Pharmacological Action
Protective Agents