The Norwegian Prednisolone in Early Psychosis Study

NCT03340909 | Terminated Phase 2 DMC

• 1 other identifier: 2017/620/REK vest
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 3

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.

Conditions

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

Outcome Measures

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.

  6 weeks

Secondary Outcomes (8)

• Improvement of overall symptom severity after 6 and 12 months

  6 and 12 months

• Improvement of overall cognition

  1 year

• Improvement of positive symptoms

  6 weeks, 6 months, 12 months

• Improvement of negative symptoms

  6 weeks, 6 months, 12 months

• Improvement of general psychopathology

  6 weeks, 6 months, 12 months

Study Arms (2)

Prednisolone

EXPERIMENTAL

Prednisolone tablets 5 mg

Drug: Prednisolone

Placebo

PLACEBO COMPARATOR

Placebo tablets with identical appearance to the experimental drug.

Other: Placebo

Interventions

Prednisolone DRUG

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

Prednisolone

Placebo OTHER

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

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• \. 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.
• \. telaprevir and boceprevir in treatment of Hepatitis C

Sponsors & Collaborators

• Haukeland University Hospital: lead
• Helse Stavanger HF: collaborator
• St. Olavs Hospital: collaborator

Study Sites (3)

Haukeland University Hospital

Bergen, Norway

Location

Stavanger University Hospital

Stavanger, Norway

Location

St. Olavs Hospital

Trondheim, Norway

Location

Related Publications (1)

• 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 DERIVED

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Prednisolone

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Placebo-controlled randomized 1:1 comparison.

Study Record Dates

• First Submitted: November 2, 2017
• First Posted: November 14, 2017
• Study Start: February 2, 2018
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: August 1, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

NO (3)