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The Norwegian Prednisolone in Early Psychosis Study (NorPEPS)

Primary Purpose

Schizophrenia and Related Disorders, Immune Suppression, Psychosis

Status

Terminated

Phase

Phase 2

Locations

Norway

Study Type

Interventional

Intervention

Prednisolone

Placebo

About this trial

This is an interventional treatment trial for Schizophrenia and Related Disorders

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

A DSM-IV-R diagnosis of: 295.x (schizophrenia, schizophreniform disorder, or schizoaffective disorder) or 298.9 (psychosis NOS)
Onset of psychosis no longer than 5 years ago
Minimum total PANSS score of 60 Age 18 -70 years.
Patients are treated with antipsychotic medication
Written informed consent is obtained
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:

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.
Presence of diabetes mellitus or random (non-fasting) glucose levels exceeding 11 mmol/L at screening, or family history of diabetes.
Body Mass Index (BMI) of >30.0
Current or chronic use of systemic glucocorticosteroids (temporary use is permitted, if stopped before start of treatment trial)
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.
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.
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

Sites / Locations

Haukeland University Hospital
Stavanger University Hospital
St. Olavs Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Prednisolone

Placebo

Arm Description

Prednisolone tablets 5 mg

Placebo tablets with identical appearance to the experimental drug.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Improvement of overall symptom severity after 6 and 12 months

Improvement of overall cognition

Cognitive functioning as measured by the Brief Assessment of Cognition in Schizophrenia (BACS).

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

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

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

Improvement og the Global Assessment of Functioning scale (GAF)

GAF is scored between 1 (lowest possible functioning) and 100 (best possible functioning).

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).

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.

Full Information

NCT ID

NCT03340909

First Posted

November 2, 2017

Last Updated

July 28, 2022

Sponsor

Haukeland University Hospital

Collaborators

Helse Stavanger HF, St. Olavs Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03340909

Brief Title

The Norwegian Prednisolone in Early Psychosis Study

Acronym

NorPEPS

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Terminated

Why Stopped

Stopped because of COVID 19 pandemic

Study Start Date

February 2, 2018 (Actual)

Primary Completion Date

December 31, 2021 (Actual)

Study Completion Date

December 31, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Haukeland University Hospital

Collaborators

Helse Stavanger HF, St. Olavs Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Schizophrenia and Related Disorders, Immune Suppression, Psychosis, Cognitive Change

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Placebo-controlled randomized 1:1 comparison.

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Prednisolone

Arm Type

Experimental

Arm Description

Prednisolone tablets 5 mg

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo tablets with identical appearance to the experimental drug.

Intervention Type

Drug

Intervention Name(s)

Prednisolone

Intervention Description

Prednisolone tablets initiated at 40 mg for three days, after which it will be phased out within 6 weeks after start

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Placebo tablets initiated at 40 mg for three days, after which it will be phased out within 6 weeks after start

Primary Outcome Measure Information:

Title

Improvement of overall symptom severity

Description

Time Frame

6 weeks

Secondary Outcome Measure Information:

Title

Improvement of overall symptom severity after 6 and 12 months

Description

Time Frame

6 and 12 months

Title

Improvement of overall cognition

Description

Cognitive functioning as measured by the Brief Assessment of Cognition in Schizophrenia (BACS).

Time Frame

1 year

Title

Improvement of positive symptoms

Description

Time Frame

6 weeks, 6 months, 12 months

Title

Improvement of negative symptoms

Description

Time Frame

6 weeks, 6 months, 12 months

Title

Improvement of general psychopathology

Description

Time Frame

6 weeks, 6 months, 12 months

Title

Improvement og the Global Assessment of Functioning scale (GAF)

Description

GAF is scored between 1 (lowest possible functioning) and 100 (best possible functioning).

Time Frame

6 weeks, 6 months, 12 months

Title

Change of depressive symptoms

Description

Time Frame

6 weeks, 6 months, 12 months

Title

Number of participants with treatment-related adverse events as assessed by the UKU Side Effects Rating Scale

Description

Occurrence and severity of severe adverse events and suspected unexpected severe adverse reaction as measured by the UKU Side Effects Rating Scale.

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: A DSM-IV-R diagnosis of: 295.x (schizophrenia, schizophreniform disorder, or schizoaffective disorder) or 298.9 (psychosis NOS) Onset of psychosis no longer than 5 years ago Minimum total PANSS score of 60 Age 18 -70 years. Patients are treated with antipsychotic medication Written informed consent is obtained 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: 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. Presence of diabetes mellitus or random (non-fasting) glucose levels exceeding 11 mmol/L at screening, or family history of diabetes. Body Mass Index (BMI) of >30.0 Current or chronic use of systemic glucocorticosteroids (temporary use is permitted, if stopped before start of treatment trial) 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. 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. 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Erik Johnsen, MD, PhD

Organizational Affiliation

Haukeland University Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Solveig Klæbo Reitan, MD, PhD

Organizational Affiliation

St. Olavs Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Helle Schøyen, MD, PhD

Organizational Affiliation

Helse Stavanger HF

Official's Role

Principal Investigator

Facility Information:

Facility Name

Haukeland University Hospital

City

Bergen

Country

Norway

Facility Name

Stavanger University Hospital

City

Stavanger

Country

Norway

Facility Name

St. Olavs Hospital

City

Trondheim

Country

Norway

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

32513294

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.

Results Reference

derived

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The Norwegian Prednisolone in Early Psychosis Study

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