Prednisolone Addition for Patients With Recent-onset Psychotic Disorder

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02949232
Recruitment Status : Unknown
Verified October 2016 by Iris Sommer, UMC Utrecht.
Recruitment status was:  Recruiting
First Posted : October 31, 2016
Last Update Posted : November 1, 2016
Information provided by (Responsible Party):
Iris Sommer, UMC Utrecht

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.

Condition or disease Intervention/treatment Phase
Schizophrenia Schizoaffective Disorder Schizophreniform Disorder Psychotic Disorder NOS Drug: Prednisolone Drug: Placebo Oral Tablet Phase 4

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Prednisolone Addition for Patients With Recent-onset Psychotic Disorder: the Role of Immune-modulating Strategies in the Treatment of Psychosis
Study Start Date : July 2014
Estimated Primary Completion Date : July 2018
Estimated Study Completion Date : July 2018

Arm Intervention/treatment
Experimental: Prednisolone
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
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 Comparator: Placebo Oral Tablet
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
Dosing following the tapering scheme of the treatment of the treatment arm

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. Improvement in cognitive functioning [ Time Frame: 6 months ]
    Cognitive functioning is measured through the Brief Assessment of Cognition in Schizophrenia (BACS).

  2. Change in GAF scores [ Time Frame: 1 year ]
    Global Assessment of Functioning

  3. Measurement of various immunological biomarkers [ Time Frame: 6 months ]
  4. Improvement of PANSS scores in follow-up [ Time Frame: 1 year ]
  5. Score on the Calgary Depression Scale for Schizophrenia (CDSS) [ Time Frame: 6 weeks ]
  6. Incidences of key SAEs and SUSARs [ Time Frame: 1 year ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02949232

Contact: Inge Winter, Dr. +31 88 755 5555

ZNA Recruiting
Antwerp, Belgium, 2060
Contact: Jurjen Luykx, Dr.    +32 32177881   
University Aarhus Not yet recruiting
Risskov, Denmark, 8240
Contact: Micheal Benros, Dr.    +45 26255239   
Yulius Recruiting
Sliedrecht, Netherlands, 3361XV
Contact: Arthur van Gool, Dr.    +31 88 40 50 600   
UMC Utrecht Recruiting
Utrecht, Netherlands, 3508 GA
Contact: Iris Sommer, Prof. Dr.    +31 88 755 6370   
Sponsors and Collaborators
UMC Utrecht
Principal Investigator: Iris Sommer, Prof. Dr. UMC Utrecht

Responsible Party: Iris Sommer, Prof. Dr., UMC Utrecht Identifier: NCT02949232     History of Changes
Other Study ID Numbers: NL46653
First Posted: October 31, 2016    Key Record Dates
Last Update Posted: November 1, 2016
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Psychotic Disorders
Mental Disorders
Pathologic Processes
Schizophrenia Spectrum and Other Psychotic Disorders
Prednisolone acetate
Methylprednisolone acetate
Methylprednisolone Hemisuccinate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents