SchizophreniaPhase 4NCT02949232
Prednisolone Addition for Patients With Recent-onset Psychotic Disorder
A Phase 4 study testing Prednisolone in people with Schizophrenia and Schizoaffective Disorder, run by UMC Utrecht at 4 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder
- What is being tested?
- Prednisolone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 4 sitesin 3 countries
- Study dates
- Jul 2014to May 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
About this study
Official title: Prednisolone Addition for Patients With Recent-onset Psychotic Disorder: the Role of Immune-modulating Strategies in the Treatment of Psychosis
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.
Read the 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.
- Conditions
- Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder, Psychotic Disorder NOS
- Being tested
- Prednisolone, Placebo Oral Tablet
- Medical subject headings
- Schizophrenia, Psychotic Disorders, Mental Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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).
Placebo Oral TabletDrug
Dosing following the tapering scheme of the treatment of the treatment arm
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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 Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 weeks
Secondary outcomes (6)
Improvement in cognitive functioning
Cognitive functioning is measured through the Brief Assessment of Cognition in Schizophrenia (BACS).
Measured: 6 months
Change in GAF scores
Global Assessment of Functioning
Measured: 1 year
Measurement of various immunological biomarkers
Cytokine panels will be analysed
Measured: 6 months
Improvement of PANSS scores in follow-up
PANSS follow-up; 4 months, 6 months and 12 months
Measured: 1 year
Score on the Calgary Depression Scale for Schizophrenia (CDSS)
CDSS scores will be analysed
Measured: 6 weeks
Incidences of key SAEs and SUSARs
Safety analyses
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2016 (estimated)
- Study startJul 2014
- Primary completionMay 2019
- Study completionMay 2019
Why it stopped: Difficulties with recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by UMC UtrechtThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Iris Sommer, UMC Utrecht
- Investigators
- Iris Sommer, Prof. Dr., Principal investigator, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02949232
- Sponsor's protocol ID
- NL46653
- Status last verified
- Jun 2019
- First submitted
- 27 Oct 2016
- Last updated
- 24 Jun 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 33711681
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prednisolone Addition for Patients With Recent-onset Psychotic Disorder: the Role of Immune-modulating Strategies in the Treatment of Psychosis
- ClinicalTrials.gov ID
- NCT02949232
- Acronym / sponsor ID
- NL46653
- Conditions
- Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder, Psychotic Disorder NOS
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulties with recruitment
- Enrolment
- 42 participants (actual)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- Study start
- Jul 2014 (actual)
- Primary completion
- May 2019 (actual)
- Study completion
- May 2019 (actual)
- First posted
- 31 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prednisolone | Experimental | Drug: PrednisolonePrednisolone 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 Oral Tablet | Placebo comparator | Drug: Placebo Oral TabletPlacebo 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 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Prednisoloneprednisolone 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). | Drug | Prednisolone |
| Placebo Oral TabletDosing following the tapering scheme of the treatment of the treatment arm | Drug | Placebo Oral Tablet |
Primary outcome
Change in symptom severity
Time frame: 6 weeks
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 secondary outcomes
Improvement in cognitive functioning
Time frame: 6 months
Change in GAF scores
Time frame: 1 year
Measurement of various immunological biomarkers
Time frame: 6 months
Improvement of PANSS scores in follow-up
Time frame: 1 year
Score on the Calgary Depression Scale for Schizophrenia (CDSS)
Time frame: 6 weeks
Incidences of key SAEs and SUSARs
Time frame: 1 year
Results and safety
The study was stopped early (reason given: Difficulties with recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2019.
- Derived from this study: PubMed 33711681Nasib 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Iris Sommer, Prof. Dr. principal investigator
UMC Utrecht
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Prednisolone in people with Schizophrenia and Schizoaffective Disorder, run by UMC Utrecht at 4 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Netherlands, Belgium, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Difficulties with recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in symptom severity (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02949232, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2019.