Cognitive Change, Immune Suppression, Psychosis, Schizophrenia and Related Disorders
Conditions
Brief summary
Objective: The primary objective of this trial is to investigate whether prednisolone improves symptom severity as compared to placebo when given in addition to antipsychotic medication to patients with early-stage psychotic disorder. Secondary objectives include improvement of cognitive functioning and positive, negative and general psychopathological symptoms as well as general functioning. Study design: Randomized placebo-controlled double-blind trial. Study population: 90 men and women, with an age of 18 years and older, diagnosed with schizophrenia spectrum disorder. The time interval between the onset of psychosis and study entry should not exceed five years and CRP level should be at least 3.9 mg/L. Intervention: Patients will be randomized 1:1 to either prednisolone or placebo daily for a period of 6 weeks. Identical tablets will be administered. Prednisolone will be initiated at 40 mg for three days, after which it will be phased out within 6 weeks after start, following current treatment guidelines. Main study parameters/endpoints: Primary outcome is change in symptom severity, expressed as a change in total score on the Positive and Negative Symptom Scale (PANSS) from baseline to end of the 6-week treatment. Secondary outcomes are a 6-month follow-up assessment of PANSS, cognitive functioning (measured through a repeatable neurocognitive battery, change in GAF scores and the measurement of various immunological biomarkers. In post-hoc analyses, attempts will be made to identify baseline blood markers with predictive properties regarding improvement in the anti-inflammatory drug treatment arm. Expected benefits for consumers and care givers: A decrease in symptom severity is expected, as low grade brain inflammation may be associated with psychotic symptoms. The results may give raise to a new line of scientific research as well as treatment options for a disabling disorder.
Interventions
DRUGPrednisolone
Prednisolone tablets initiated at 40 mg for three days, after which it will be phased out within 6 weeks after start
OTHERPlacebo
Placebo tablets initiated at 40 mg for three days, after which it will be phased out within 6 weeks after start
Sponsors
Helse Stavanger HF
St. Olavs Hospital
Haukeland University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Placebo-controlled randomized 1:1 comparison.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. A DSM-IV-R diagnosis of: 295.x (schizophrenia, schizophreniform disorder, or schizoaffective disorder) or 298.9 (psychosis NOS) 2. Onset of psychosis no longer than 5 years ago 3. Minimum total PANSS score of 60 Age 18 -70 years. 4. Patients are treated with antipsychotic medication 5. Written informed consent is obtained 6. Female patients of childbearing potential need to utilize a proper method of contraception (the pill, vaginal ring, hormonal patch, intrauterine device, cervical cap, condom, contraceptive injection, diaphragm) in case of sexual intercourse during the study.
Exclusion criteria
1. Presence of any of the contra-indications of prednisolone as reported in the SPC. These include hypersensitivity to any ingredients in the formulation, systemic infections unless specific anti-infective therapy is employed, patients with ocular herpes simplex due to the possibility of perforation, recent vaccination with live or weakened virus or bacteria. Also the following special warnings in the SPC will represent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Improvement of overall symptom severity | 6 weeks | Overall symptom severity measured by the Positive and Negative Syndrome Scale. 30 items rated between 1 (symptom not present) and 7 (symptom present in the most severe degree. The sum score constitutes the overall symptom severity, and ranges between 30 - 210 Points. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improvement of overall cognition | 1 year | Cognitive functioning as measured by the Brief Assessment of Cognition in Schizophrenia (BACS). |
| Improvement of positive symptoms | 6 weeks, 6 months, 12 months | The Positive subscale score as measured by the Positive and Negative Syndrome Scale. 7 items rated between 1 (symptom not present) and 7 (symptom present in the most severe degree. The range is between 7-49 points |
| Improvement of negative symptoms | 6 weeks, 6 months, 12 months | The Negative subscale score as measured by the Positive and Negative Syndrome Scale. 7 items rated between 1 (symptom not present) and 7 (symptom present in the most severe degree. The range is between 7-49 points |
| Improvement of overall symptom severity after 6 and 12 months | 6 and 12 months | Overall symptom severity measured by the Positive and Negative Syndrome Scale. 30 items rated between 1 (symptom not present) and 7 (symptom present in the most severe degree. The sum score constitutes the overall symptom severity, and ranges between 30 - 210 Points. |
| Improvement og the Global Assessment of Functioning scale (GAF) | 6 weeks, 6 months, 12 months | GAF is scored between 1 (lowest possible functioning) and 100 (best possible functioning). |
| Change of depressive symptoms | 6 weeks, 6 months, 12 months | Severity of depression is assessed using the Calgary Depression Scale for Schizophrenia, which has 9 items scored as 0 (symptom not present), 1 (mild degree), 2 (moderate degree), or 3 (severe degree of symptom). This makes a possible sub score range between 0 and 27). |
| Number of participants with treatment-related adverse events as assessed by the UKU Side Effects Rating Scale | 12 months | Occurrence and severity of severe adverse events and suspected unexpected severe adverse reaction as measured by the UKU Side Effects Rating Scale. |
| Improvement of general psychopathology | 6 weeks, 6 months, 12 months | The general psychopathology subscale as measured by the Positive and Negative Syndrome Scale. 16 items rated between 1 (symptom not present) and 7 (symptom present in the most severe degree. The range is between 16-112 points |
Countries
Norway
Outcome results
None listed