Quetiapine and the Dopaminergic Epigenetic Control

Sponsor

University of Erlangen-Nürnberg Medical School (Other)

Overall Status

Completed

CT.gov ID

NCT00370500

Collaborator

AstraZeneca (Industry)

100

Enrollment

Location

Arm

Duration (Months)

6.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

BACKGROUND:

Epigenetic modifications such as DNA-methylation and histone acetylation are known to be involved in the pathophysiology of schizophrenia. Aim of the present study is to investigate

whether differences in the methylation pattern of the promoters of dopaminergic genes exist between schizophrenic patients and healthy controls and
whether treatment with the second generation antipsychotic quetiapine leads to changes in the methylation pattern of those genes in patients suffering from schizophrenia.

STUDY DESIGN AND METHODS:

50 male patients and 50 male controls are to be enrolled into the study. Patients will be treated with quetiapine for 3 weeks. Blood samples will be drawn before treatment and after three weeks to measure DNA-methylation status. Clinical characterisation includes PANSS, AIMS, BDI. Healthy probands will not be treated.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: Quetiapine fumarate	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

100 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Quetiapine and the Dopaminergic Epigenetic Control - a Pilot Study

Study Start Date :

Apr 1, 2007

Actual Primary Completion Date :

Jul 1, 2008

Actual Study Completion Date :

Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A There is only one arm in this study. All probands receive quetiapine.	Drug: Quetiapine fumarate Dosage and frequency are judged by the study physician. The dosage must not excess 800mg/d. Other Names: Seroquel(R)

Arm

Intervention/Treatment

Experimental: A

There is only one arm in this study. All probands receive quetiapine.

Drug: Quetiapine fumarate

Dosage and frequency are judged by the study physician. The dosage must not excess 800mg/d.

Other Names:

Seroquel(R)

Outcome Measures

Primary Outcome Measures

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). [6 month]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Inclusion criteria:

For inclusion in the study subjects must fulfil all of the following criteria:

Provision of written informed consent
A diagnosis of schizophrenia by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV)
Able to understand and comply with the requirements of the study
Age 18 - 65 years

Exclusion criteria:

Any of the following is regarded as a criterion for exclusion from the study:

Any DSM-IV Axis I disorder not defined in the inclusion criteria
Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others
Known intolerance or lack of response to quetiapine fumarate, as judged by the investigator
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
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
Administration of a depot antipsychotic injection within one dosing interval (for the depot) before inclusion
Substance or alcohol dependence at enrolment (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM-IV criteria
Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse by DSM-IV criteria within 4 weeks prior to enrolment
Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment
Unstable or inadequately treated medical illness (e.g. diabetes, angina pectoris, hypertension) as judged by the investigator
Involvement in the planning and conduct of the study
Previous enrolment in the present study.
Participation in another drug trial within 4 weeks prior enrolment into this study or longer in accordance with local requirements
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.
Previous history of major head injuries or neurological disorders
Intake of homocysteine lowering vitamins (folate, B12, B6)
Renal failure
Intake of nutritional derivatives which influence epigenetic patterns (butyrate from milk products, tea polyphenol or epigallo-catechin-3-gallate which inhibits DNMT)