Clinical trial NCT02949232: 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
Overall status: TERMINATED
Phase: PHASE4
Conditions: Schizophrenia
Schizoaffective Disorder
Schizophreniform Disorder
Psychotic Disorder NOS
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
First posted: 2016-10-31
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 7 years ago
3. Minimum total PANSS score of 60
4. Age 18 -70 years
5. Patients are treated with antipsychotic medication
6. Written informed consent is obtained
7. 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:

1. Presence of any of the contra-indications of prednisolone as reported in the SPC.
2. 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.
3. Body Mass Index (BMI) of \>30.0
4. Current or chronic use of systemic glucocorticosteroids (temporary use is permitted, if stopped 1 month 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.
7. 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

Primary outcomes:
measure: Change in symptom severity
timeFrame: 6 weeks
Secondary outcomes:
measure: Improvement in cognitive functioning
timeFrame: 6 months
measure: Change in GAF scores
timeFrame: 1 year
measure: Measurement of various immunological biomarkers
timeFrame: 6 months
measure: Improvement of PANSS scores in follow-up
timeFrame: 1 year
measure: Score on the Calgary Depression Scale for Schizophrenia (CDSS)
timeFrame: 6 weeks
measure: Incidences of key SAEs and SUSARs
timeFrame: 1 year
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: ZNA
city: Risskov
country: Denmark
facility: University Aarhus
city: Sliedrecht
country: Netherlands
facility: Yulius
city: Utrecht
country: Netherlands
facility: UMC Utrecht
Study officials:
affiliation: UMC Utrecht
name: Iris Sommer, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
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.