E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients suffering from schizophrenia (ICD10: F20.x) Healthy controls |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10039628 |
E.1.2 | Term | Schizophrenia and other psychotic disorders |
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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 |
To determine the dynamics of the DNA methylation of the DAT gene due to treatment with quetiapine in schizophrenic patients. |
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E.2.2 | Secondary objectives of the trial |
To determine whether quetiapine influences the global and gene-specific epigenetic control of genes belonging to the dopaminergic or serotonergic pathways. To analyse, whether treatment with quetiapine interferes with possible differences between patients and controls. To further determine, if changes in DNA methylation correlate with efficacy, safety and tolerability of quetiapine treatment, measured using CGI-S, PANSS and AIMS (safety). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provision of written informed consent 2. A diagnosis of schizophrenia by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV) 3. Able to understand and comply with the requirements of the study 4. Age: 18 – 65 years
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E.4 | Principal exclusion criteria |
1. Any DSM-IV Axis I disorder not defined in the inclusion criteria 2. Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others 3. Known intolerance or lack of response to quetiapine fumarate, as judged by the investigator 4. Use of any of the following cytochrome P450 3A4 inhibitors in the 14 days preceding enrolment including but not limited to: ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, troleandomycin, indinavir, nelfinavir, ritonavir, fluvoxamine and saquinavir 5. Use of any of the following cytochrome P450 inducers in the 14 days preceding enrollment including but not limited to: phenytoin, carbamazepine, barbiturates, rifampin, St. John’s Wort, and glucocorticoids 6. Administration of a depot antipsychotic injection within one dosing interval (for the depot) before inclusion 7. Substance or alcohol dependence at enrolment (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM-IV criteria 8. Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse by DSM-IV criteria within 4 weeks prior to enrolment 9. Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment 10. Unstable or inadequately treated medical illness (e.g. diabetes, angina pectoris, hypertension) as judged by the investigator 11. Involvement in the planning and conduct of the study 12. Previous enrolment in the present study. 13. Participation in another drug trial within 4 weeks prior enrolment into this study or longer in accordance with local requirements 14. Actual treatment with clozapine or clozapine treatment during the previous three month. Other antipsychotic drugs will be allowed, if intake can be terminated during the two day wash out period. 15. Previous history of major head injuries or neurological disorders 16. Intake of homocysteine lowering vitamins (folate, B12, B6) 17. Renal failure 18. Intake of nutritional derivatives which influence epigenetic patterns (butyrate from milk products, tea polyphenol or epigallo-catechin-3-gallate which inhibits DNMT)
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary variable is the amount of methylated vs. unmethylated promoter specific DNA in the DAT gene of patients before and after treatment with quetiapine (within group comparison). |
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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 | No |
E.6.4 | Safety | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Basic sciene - discovering modes of drug action |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
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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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |