The Norwegian Prednisolone in Early Psychosis Study

• Prednisolone (Drug): Prednisolone tablets initiated at 40 mg for three days, after which it will be phased out within 6 weeks after start
• Placebo (Other): Placebo tablets initiated at 40 mg for three days, after which it will be phased out within 6 weeks after start

Primary outcomes

• 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 outcomes

• 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 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 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
• 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.

Sex: All, ages: 18 Years to 70 Years

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 exclusion criteria: Existing or previous history of severe affective disorders in themselves or in their first degree relatives, including depressive or bipolar disorders or previous steroid psychosis, glaucoma or family history of glaucoma, hypertension or heart failure, liver impairment and/ or failure, epilepsy, osteoporosis, peptic ulceration, previous steroid myopathy, renal insufficiency, history of tuberculosis or x-ray changes characteristic of tuberculosis, recent myocardial infarction, chickenpox, measles.
2. Presence of diabetes mellitus or random (non-fasting) glucose levels exceeding 11 mmol/L at screening, or family history of diabetes.
3. Body Mass Index (BMI) of >30.0
4. Current or chronic use of systemic glucocorticosteroids (temporary use is permitted, if stopped before start of treatment trial)
5. Chronic use of non-steroidal anti-inflammatory drugs, defined as daily use during more than 2 months. Intermittent use is permitted, if stopped at least 1 month before start of treatment trial.
6. Pregnancy or breast-feeding. A urine pregnancy test will be performed at screening and then after 6 weeks of treatment and the event of treatment discontinuation.
7. Concurrent use of certain types of medication:

1\. liver enzyme inducing medication such as carbamazepine, riphampicine, primidone, barbiturates and phenytoine 2. HAART (both HIV protease inhibitors and (non)-nucleoside reverse transcriptase inhibitors), especially efavirenz, ritonavir and lopinavir.

3\. telaprevir and boceprevir in treatment of Hepatitis C

• Results publication: Nasib LG, Sommer IE, Winter-van Rossum I, de Vries J, Gangadin SS, Oomen PP, Judge G, Blom RE, Luykx JJ, van Beveren NJM, Veen ND, Kroken RA, Johnsen EL. Prednisolone versus placebo addition in the treatment of patients with recent-onset psychotic disorder: a trial design. Trials. 2020 Jun 8;21(1):492. doi: 10.1186/s13063-020-04365-4. PMID 32513294

• Erik Johnsen, MD, PhD, Principal investigator, Haukeland University Hospital
• Solveig Klæbo Reitan, MD, PhD, Principal investigator, St. Olavs Hospital
• Helle Schøyen, MD, PhD, Principal investigator, Helse Stavanger HF