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Prednisolone Addition for Patients With Recent-onset Psychotic Disorder

Primary Purpose

Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder

Status

Terminated

Phase

Phase 4

Locations

International

Study Type

Interventional

Intervention

Prednisolone

Placebo Oral Tablet

About this trial

This is an interventional treatment trial for Schizophrenia

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 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.

Exclusion Criteria:

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:

1. liver enzyme inducing medication such as carbamazepine, riphampicine, primidone, barbiturates and phenytoine

2. HAART medication (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

ZNA
University Aarhus
Yulius
UMC Utrecht

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Prednisolone

Placebo Oral Tablet

Arm Description

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).

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Improvement in cognitive functioning

Cognitive functioning is measured through the Brief Assessment of Cognition in Schizophrenia (BACS).

Change in GAF scores

Global Assessment of Functioning

Measurement of various immunological biomarkers

Cytokine panels will be analysed

Improvement of PANSS scores in follow-up

PANSS follow-up; 4 months, 6 months and 12 months

Score on the Calgary Depression Scale for Schizophrenia (CDSS)

CDSS scores will be analysed

Incidences of key SAEs and SUSARs

Safety analyses

Full Information

NCT ID

NCT02949232

First Posted

October 27, 2016

Last Updated

June 21, 2019

Sponsor

UMC Utrecht

1. Study Identification

Unique Protocol Identification Number

NCT02949232

Brief Title

Prednisolone Addition for Patients With Recent-onset Psychotic Disorder

Official Title

Prednisolone Addition for Patients With Recent-onset Psychotic Disorder: the Role of Immune-modulating Strategies in the Treatment of Psychosis

Study Type

Interventional

2. Study Status

Record Verification Date

June 2019

Overall Recruitment Status

Terminated

Why Stopped

Difficulties with recruitment

Study Start Date

July 2014 (Actual)

Primary Completion Date

May 2019 (Actual)

Study Completion Date

May 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

UMC Utrecht

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

In the current study, the investigators aim to investigate the effect of additional treatment with prednisolone on symptomatic improvement, global functioning, cognition and on immunological parameters in patients with early-stage psychotic disorder, applying a randomized double-blind placebo-controlled add-on design. A placebo-controlled design was chosen in order to differentiate between clinical effects of prednisolone and effects associated with experimental treatment, such as induced expectations of participants. Prednisolone or placebo is provided next to existent antipsychotic medication as the investigators do not intend to replace existing treatment, this study being a Proof of Concept trial. It would carry considerable risks for patients to taper down existent antipsychotic medication and randomize patients to either placebo or a type of therapy for which the efficacy still has to be proven, even for a short period of time. 90 patients with schizophrenia, schizoaffective or schizophreniform disorder, or psychotic disorder NOS (not otherwise specified) will be included, with an age of 18-70 years and a time interval between the onset of psychosis and study entry not exceeding seven years. All 90 in- and outpatients will be randomized 1:1 to either prednisolone or placebo daily for 6 weeks. Prednisolone will be initiated at 40mg/day for 3 days and the 4 remaining days of the first week 30mg/dag will be used. During the treatment period, patients will be seen at weekly intervals to assess symptom severity, depressive mood and suicidal ideation, global functioning and side effects.

6. Conditions and Keywords

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

Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder, Psychotic Disorder NOS

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

42 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Prednisolone

Arm Type

Experimental

Arm Description

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).

Arm Title

Placebo Oral Tablet

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Prednisolone

Intervention Description

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).

Intervention Type

Drug

Intervention Name(s)

Placebo Oral Tablet

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in symptom severity

Description

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.

Time Frame

6 weeks

Secondary Outcome Measure Information:

Title

Improvement in cognitive functioning

Description

Cognitive functioning is measured through the Brief Assessment of Cognition in Schizophrenia (BACS).

Time Frame

6 months

Title

Change in GAF scores

Description

Global Assessment of Functioning

Time Frame

1 year

Title

Measurement of various immunological biomarkers

Description

Cytokine panels will be analysed

Time Frame

6 months

Title

Improvement of PANSS scores in follow-up

Description

PANSS follow-up; 4 months, 6 months and 12 months

Time Frame

1 year

Title

Score on the Calgary Depression Scale for Schizophrenia (CDSS)

Description

CDSS scores will be analysed

Time Frame

6 weeks

Title

Incidences of key SAEs and SUSARs

Description

Safety analyses

Time Frame

1 year

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 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. Exclusion Criteria: 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: 1. liver enzyme inducing medication such as carbamazepine, riphampicine, primidone, barbiturates and phenytoine 2. HAART medication (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

Iris Sommer, Prof. Dr.

Organizational Affiliation

UMC Utrecht

Official's Role

Principal Investigator

Facility Information:

Facility Name

ZNA

City

Antwerp

ZIP/Postal Code

2060

Country

Belgium

Facility Name

University Aarhus

City

Risskov

ZIP/Postal Code

8240

Country

Denmark

Facility Name

Yulius

City

Sliedrecht

ZIP/Postal Code

3361XV

Country

Netherlands

Facility Name

UMC Utrecht

City

Utrecht

ZIP/Postal Code

3508 GA

Country

Netherlands

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

33711681

Citation

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.

Results Reference

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Prednisolone Addition for Patients With Recent-onset Psychotic Disorder

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