The Norwegian Prednisolone in Early Psychosis Study (NorPEPS)

The Norwegian Prednisolone in Early Psychosis Study - NorPEPS. The Role of Immune-modulating Strategies in the Treatment of Psychosis

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.

Study Overview

• Status: Terminated
• Conditions: Cognitive Change; Psychosis; Schizophrenia and Related Disorders; Immune Suppression
• Intervention / Treatment: Drug: Prednisolone; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• Norway
  • Bergen, Norway
    • Haukeland University Hospital
  • Stavanger, Norway
    • Stavanger University Hospital
  • Trondheim, Norway
    • St. Olavs Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prednisolone; Prednisolone tablets 5 mg	Drug: Prednisolone; Prednisolone tablets initiated at 40 mg for three days, after which it will be phased out within 6 weeks after start
Placebo Comparator: Placebo; Placebo tablets with identical appearance to the experimental drug.	Other: Placebo; Placebo tablets initiated at 40 mg for three days, after which it will be phased out within 6 weeks after start

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of overall symptom severity	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.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of overall symptom severity after 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.	6 and 12 months
Improvement of overall cognition	Cognitive functioning as measured by the Brief Assessment of Cognition in Schizophrenia (BACS).	1 year
Improvement of positive symptoms	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	6 weeks, 6 months, 12 months
Improvement of negative symptoms	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	6 weeks, 6 months, 12 months
Improvement of general psychopathology	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	6 weeks, 6 months, 12 months
Improvement og the Global Assessment of Functioning scale (GAF)	GAF is scored between 1 (lowest possible functioning) and 100 (best possible functioning).	6 weeks, 6 months, 12 months
Change of depressive symptoms	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).	6 weeks, 6 months, 12 months
Number of participants with treatment-related adverse events as assessed by the UKU Side Effects Rating Scale	Occurrence and severity of severe adverse events and suspected unexpected severe adverse reaction as measured by the UKU Side Effects Rating Scale.	12 months

Collaborators and Investigators

• Sponsor: Haukeland University Hospital
• Collaborators: Helse Stavanger HF; St. Olavs Hospital
• Investigators: Principal Investigator: Erik Johnsen, MD, PhD, Haukeland University Hospital; Principal Investigator: Solveig Klæbo Reitan, MD, PhD, St. Olavs Hospital; Principal Investigator: Helle Schøyen, MD, PhD, Helse Stavanger HF

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2018
• Primary Completion (Actual): December 31, 2021
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: November 2, 2017
• First Submitted That Met QC Criteria: November 8, 2017
• First Posted (Actual): November 14, 2017

Study Record Updates

• Last Update Posted (Actual): August 1, 2022
• Last Update Submitted That Met QC Criteria: July 28, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders; Mental Disorders; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisolone
• Other Study ID Numbers: 2017/620/REK vest

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No