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TerminatedNCT03340909NorPEPSUpdated Aug 1, 2022

The Norwegian Prednisolone in Early Psychosis Study

A Phase 2 interventional study of Prednisolone and Placebo in Schizophrenia and Related Disorders, Immune Suppression and Psychosis, sponsored by Haukeland University Hospital. Terminated at 3 sites in Norway. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2022-08-01.

Sponsored by Haukeland University Hospital · Phase 2, Interventional, and Treatment

Why this study was terminated
Stopped because of COVID 19 pandemic
Phase
Phase 2
Study type
Interventional
Enrollment
12
Allocation
Randomized
Ages
18 Years to 70 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Schizophrenia and Related Disorders
  • Immune Suppression
  • Psychosis
  • Cognitive Change
03

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts 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

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.
  1. telaprevir and boceprevir in treatment of Hepatitis C
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
12 participants (actual)

Study arms

  • Experimental
    Prednisolone

    Prednisolone tablets 5 mg

    Drug: Prednisolone

  • Placebo comparator
    Placebo

    Placebo tablets with identical appearance to the experimental drug.

    Other: Placebo

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

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 6 weeks

Secondary outcomes

  1. 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.

    Time frame: 6 and 12 months

  2. Improvement of overall cognition

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

    Time frame: 1 year

  3. 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

    Time frame: 6 weeks, 6 months, 12 months

  4. 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

    Time frame: 6 weeks, 6 months, 12 months

  5. 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

    Time frame: 6 weeks, 6 months, 12 months

  6. Improvement og the Global Assessment of Functioning scale (GAF)

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

    Time frame: 6 weeks, 6 months, 12 months

  7. 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).

    Time frame: 6 weeks, 6 months, 12 months

  8. 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.

    Time frame: 12 months

06

Study locations

3 sites
  • Haukeland University Hospital
    Bergen, Norway
  • Stavanger University Hospital
    Stavanger, Norway
  • St. Olavs Hospital
    Trondheim, Norway
07

References and documents

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. PubMed 32513294 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03340909
Lead sponsor
Haukeland University Hospital
Collaborators
Helse Stavanger HF, St. Olavs Hospital
Responsible party
Sponsor
First posted
Nov 14, 2017
Start date
Feb 2, 2018
Primary completion
Dec 31, 2021
Completion
Dec 31, 2021
Last update
Aug 1, 2022

Study contacts

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

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
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