Psychotic Disorders, Schizoaffective Disorder, Schizophrenia, Schizophreniform Disorders
Conditions
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
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).
Interventions
DRUGVitamins E + C
RRR-alpha-tocopherol 392 mg + slow-release ascorbic acid 1000 mg per day, for 16 weeks
OTHEREtyl EPA (placebo)
Paraffin oil. Capsules, each 0.5 g.
OTHERVitamins E+C (placebo)
Tablets containing dicalciumphosphate
DRUGEthyl-eicosapentaenoic acid (EPA)
Capsules, 2 g per day for 16 weeks
Sponsors
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
University Hospital, Aker
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Positive and Negative Syndrome Scale (PANSS)- Total | Baseline - 8 weeks - 16 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Glucose | Weeks 0, 16 | Serum - fasting |
| Cholesterol | Weeks 0, 16 | Serum - fasting |
| Triglycerides | Weeks 0, 16 | Serum - fasting |
| 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 |
| PANSS Subscales Negative, Positive, General Psychopathology | Weeks 0, 8, 16 | — |
| 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 |
| Sodium | Weeks 0, 16 | Serum |
Countries
Norway
Outcome results
None listed