NCT02949232

Brief Summary

Treatment with prednisolone can be used as a proof of concept to investigate the possibility of immune modulation as a treatment for schizophrenia. It is expected that daily treatment with prednisolone in addition to antipsychotic treatment reduces psychotic symptoms and improves cognition, as compared to placebo. The investigators propose to investigate the effects of administering the corticosteroid prednisolone versus placebo in addition to standard antipsychotic medication in patients with early stage schizophrenia or related disorders, hypothesizing that a decrease in the overall low-grade cerebral inflammation due to prednisolon treatment will be expressed as a decrease in overall symptom severity., Secondly, addition of prednisolone is hypothesised to slow down cognitive deterioration in recent-onset psychosis patients. Finally, the investigators aim to determine whether indirect immunological parameters of the hypothesised low grade inflammation status in schizophrenia are shifted due to the addition of prednisolone.

Trial Health

60
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
42

participants targeted

Target at P25-P50 for phase_4 schizophrenia

Timeline
Completed

Started Jul 2014

Longer than P75 for phase_4 schizophrenia

Geographic Reach
3 countries

4 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2014

Completed
2.3 years until next milestone

First Submitted

Initial submission to the registry

October 27, 2016

Completed
4 days until next milestone

First Posted

Study publicly available on registry

October 31, 2016

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2019

Completed
Last Updated

June 24, 2019

Status Verified

June 1, 2019

Enrollment Period

4.8 years

First QC Date

October 27, 2016

Last Update Submit

June 21, 2019

Conditions

SchizophreniaSchizoaffective DisorderSchizophreniform DisorderPsychotic Disorder NOS

Outcome Measures

Primary Outcomes (1)

  • Change in symptom severity

    Change in symptom severity is expressed as a change in total score on the Positive and Negative Symptom Scale (PANSS) from baseline to end of the 6-week treatment.

    6 weeks

Secondary Outcomes (6)

  • Improvement in cognitive functioning

    6 months

  • Change in GAF scores

    1 year

  • Measurement of various immunological biomarkers

    6 months

  • Improvement of PANSS scores in follow-up

    1 year

  • Score on the Calgary Depression Scale for Schizophrenia (CDSS)

    6 weeks

  • +1 more secondary outcomes

Study Arms (2)

Prednisolone

EXPERIMENTAL

Prednisolone will be initiated at 40 mg for three days, after which it will be phased out within 6 weeks after start, following treatment guidelines for Inflammatory Bowel Diseases (2008).

Drug: Prednisolone

Placebo Oral Tablet

PLACEBO COMPARATOR

Placebo will be initiated at 40 mg for three days, after which it will be phased out within 6 weeks after start, following the treatment schedule of the experimental arm

Drug: Placebo Oral Tablet

Interventions

PrednisoloneDRUG

prednisolone will be will be initiated during the first week at 40mg/day for 3 days and 30mg/day for 4 days, followed by a decrease of 5mg/day per week during the remaining 5 weeks; in the second week, patients will use 25 mg/day, in the third week 20 mg/day is used etc. In the last week the patients will only take prednisolone on day 1-3 and day 5 and 7; a tapering scheme in line with the treatment guidelines for Inflammatory Bowel Diseases (2008).

Prednisolone
Placebo Oral TabletDRUG

Dosing following the tapering scheme of the treatment of the treatment arm

Placebo Oral Tablet

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (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 7 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 any of the contra-indications of prednisolone as reported in the SPC.
  • Presence of diabetes mellitus or random (non-fasting) glucose levels exceeding 11 mmol/L at screening, severe heart failure, severe osteoporosis or systemic fungal infections.
  • Body Mass Index (BMI) of \>30.0
  • Current or chronic use of systemic glucocorticosteroids (temporary use is permitted, if stopped 1 month 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.
  • Concurrent use of certain types of medication:
  • \. liver enzyme inducing medication such as carbamazepine, riphampicine, primidone, barbiturates and phenytoine
  • \. HAART medication (both HIV protease inhibitors and (non)-nucleoside reverse transcriptase inhibitors), especially efavirenz, ritonavir and lopinavir.
  • \. telaprevir and boceprevir in treatment of Hepatitis C

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

ZNA

Antwerp, 2060, Belgium

Location

University Aarhus

Risskov, 8240, Denmark

Location

Yulius

Sliedrecht, 3361XV, Netherlands

Location

UMC Utrecht

Utrecht, 3508 GA, Netherlands

Location

Related Publications (1)

  • Nasib LG, Gangadin SS, Rossum IW, Boudewijns ZSRM, de Witte LD, Wilting I, Luykx J, Somers M, Veen N, van Baal C, Kahn RS, Sommer IE. The effect of prednisolone on symptom severity in schizophrenia: A placebo-controlled, randomized controlled trial. Schizophr Res. 2021 Apr;230:79-86. doi: 10.1016/j.schres.2021.01.024. Epub 2021 Mar 10.

    PMID: 33711681DERIVED

MeSH Terms

Conditions

SchizophreniaPsychotic DisordersMental Disorders

Interventions

Prednisolone

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders

Intervention Hierarchy (Ancestors)

PregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic Compounds

Study Officials

  • Iris Sommer, Prof. Dr.

    UMC Utrecht

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Prof. Dr.

Study Record Dates

First Submitted

October 27, 2016

First Posted

October 31, 2016

Study Start

July 1, 2014

Primary Completion

May 1, 2019

Study Completion

May 1, 2019

Last Updated

June 24, 2019

Record last verified: 2019-06

Data Sharing

IPD Sharing
Will not share

Locations

NL(2)BE(1)DK(1)