E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Schizophrenia, schizophreniphorm disorder, schizoaffective disorder, psychosis NOS. |
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E.1.1.1 | Medical condition in easily understood language |
Schizophrenia, psychosis-related disorder |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this trial is to investigate whether prednisolone improves overall symptom severity as compared to placebo when given for 3 days in a dosage of 40 mg and subsequently tapered during 6 weeks in addition to antipsychotic medication to patients with early-stage psychotic disorder. We expect to find an improvement of symptoms as measured by the Positive And Negative Syndrome Scale (PANSS) compared to baseline, over the course of 6 weeks (Kay et al., 1987). |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives concern PANSS-scores after 6 and 12 months of follow up, improvement in cognitive functioning as measured by the Brief Assessment of Cognition in Schizophrenia (BACS). In addition, the positive and negative symptoms as well as general psychopathology (through PANSS subscales) are compared between treatment groups, next to general functioning using the GAF (Global Assessment of Functioning) (Karterud, 1998). Severity of depression will be assessed using the Calgary Depression Scale for Schizophrenia (CDSS) (Addington et al., 1990). Also the characteristics of patients (potentially) benefiting more from immunemodulation will be investigated through the assessment of a broad panel of immune parameters in blood. Finally, safety data will be evaluated by comparing incidences (number and % of subjects with at least one occurrence) of key SAEs and SUSARs between both groups, e.g. hospitalisations. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 5 years ago
3. Minimum total PANSS score of 60 Age 18 -70 years.
4. Patients are treated with antipsychotic medication
5. Plasma level of CRP is > 3.9 mg/L at screening (through ‘high sensitivity’ measurement)
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.
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E.4 | Principal exclusion criteria |
A potential subject who meets any of the following criteria will be excluded from participation in this study in case of:
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 >27.5
4. Current or chronic use of systemic glucocorticosteroids (temporary use is permitted, if stopped 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 (both HIV protease inhibitors and (non)-nucleoside reverse transcriptase inhibitors), especially efavirenz, ritonavir and lopinavir.
3. telaprevir and boceprevir in treatment of Hepatitis C
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint is overall symptom severity as measured with the Positive and Negative Syndrome Scale (PANSS) total score (Kay et al., 1987). We will compare the effect of prednisolone versus placebo, both given in addition to antipsychotic medication, with regards to change in overall symptom severity |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
measured after 6 weeks of treatment compared to baseline |
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E.5.2 | Secondary end point(s) |
Secondary study parameters include PANSS total scores 6 months after start of the treatment, neurocognitive functioning as measured with the Brief Assessment of Cognition in Schizophrenia (BACS) and symptom severity as measured with the PANSS subscales: the positive scale, negative scale and general psychopathology scale. Furthermore, general functioning will be evaluated using the split- GAF (Karterud, 1998). These parameters will be compared between patients treated with prednisolone versus placebo. Various serum and peripheral blood mononuclear cells will be collected from all patients at baseline, as well as after 3 and 6 weeks of treatment and after 6 months of follow up. Furthermore, severity of depression will be assessed and compared between groups using the CDSS. The need to adjust current antipsychotic medication with 25% or more of the dose in Defined Daily Doses (DDD) is compared between groups. Finally, safety data will be assessed by comparing incidences (number and % of subjects with at least one occurrence) of key SAEs and SUSARs between both groups, e.g. hospitalisations. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
PANSS total scores 6 months after start of the treatment |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |