Quetiapine and the dopaminergic epigenetic control – a pilot study - Quetiapine and Epigenetics

• Conditions: Patients suffering from schizophrenia (ICD10: F20.x)Healthy controls; MedDRA version: 8.1Level: HLGTClassification code 10039628Term: Schizophrenia and other psychotic disorders

• Registration Number: EUCTR2005-006151-20-DE
• Lead Sponsor: niversity of Erlangen-Nuremberg

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-07-24
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: Not specified

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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the dynamics of the DNA methylation of the DAT gene due to treatment with quetiapine in schizophrenic patients.;Secondary Objective: 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).;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).