Clinical trial NCT03340909: The Norwegian Prednisolone in Early Psychosis Study
Official title: The Norwegian Prednisolone in Early Psychosis Study - NorPEPS. The Role of Immune-modulating Strategies in the Treatment of Psychosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Schizophrenia and Related Disorders
Immune Suppression
Psychosis
Cognitive Change
Lead sponsor: Haukeland University Hospital
Sponsor class: OTHER
Collaborators: name: Helse Stavanger HF
name: St. Olavs Hospital
First posted: 2017-11-14
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Placebo-controlled randomized 1:1 comparison.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Improvement of overall symptom severity
timeFrame: 6 weeks
Secondary outcomes:
measure: Improvement of overall symptom severity after 6 and 12 months
timeFrame: 6 and 12 months
measure: Improvement of overall cognition
timeFrame: 1 year
measure: Improvement of positive symptoms
timeFrame: 6 weeks, 6 months, 12 months
measure: Improvement of negative symptoms
timeFrame: 6 weeks, 6 months, 12 months
measure: Improvement of general psychopathology
timeFrame: 6 weeks, 6 months, 12 months
measure: Improvement og the Global Assessment of Functioning scale (GAF)
timeFrame: 6 weeks, 6 months, 12 months
measure: Change of depressive symptoms
timeFrame: 6 weeks, 6 months, 12 months
measure: Number of participants with treatment-related adverse events as assessed by the UKU Side Effects Rating Scale
timeFrame: 12 months
Other outcomes:
Locations:
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Stavanger
country: Norway
facility: Stavanger University Hospital
city: Trondheim
country: Norway
facility: St. Olavs Hospital
Study officials:
affiliation: Haukeland University Hospital
name: Erik Johnsen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Olavs Hospital
name: Solveig Klæbo Reitan, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Helse Stavanger HF
name: Helle Schøyen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.