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Quetiapine and the Dopaminergic Epigenetic Control

Primary Purpose

Schizophrenia

Status
Completed
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
Quetiapine fumarate
Sponsored by
University of Erlangen-Nürnberg Medical School
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Schizophrenia focused on measuring Schizophrenia, Dopamine transporter gene, DNA methylation, Epigenetics

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)MaleAccepts Healthy Volunteers

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)

Sites / Locations

  • Department of Psychiatry and Psychotherapy, University Erlangen-Nuremberg

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

A

Arm Description

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

Outcomes

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).

Secondary Outcome Measures

Full Information

First Posted
August 30, 2006
Last Updated
December 10, 2020
Sponsor
University of Erlangen-Nürnberg Medical School
Collaborators
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT00370500
Brief Title
Quetiapine and the Dopaminergic Epigenetic Control
Official Title
Quetiapine and the Dopaminergic Epigenetic Control - a Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
April 2007 (undefined)
Primary Completion Date
July 2008 (Actual)
Study Completion Date
July 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
University of Erlangen-Nürnberg Medical School
Collaborators
AstraZeneca

4. Oversight

Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
Keywords
Schizophrenia, Dopamine transporter gene, DNA methylation, Epigenetics

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
100 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A
Arm Type
Experimental
Arm Description
There is only one arm in this study. All probands receive quetiapine.
Intervention Type
Drug
Intervention Name(s)
Quetiapine fumarate
Other Intervention Name(s)
Seroquel(R)
Intervention Description
Dosage and frequency are judged by the study physician. The dosage must not excess 800mg/d.
Primary Outcome Measure Information:
Title
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).
Time Frame
6 month

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stefan Bleich, MD
Organizational Affiliation
University of Erlangen-Nürnberg
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Psychiatry and Psychotherapy, University Erlangen-Nuremberg
City
Erlangen
ZIP/Postal Code
91054
Country
Germany

12. IPD Sharing Statement

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Quetiapine and the Dopaminergic Epigenetic Control

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