Quetiapine and the Dopaminergic Epigenetic Control

NCT ID: NCT00370500

Last Updated: 2020-12-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-30
• Study Completion Date: 2008-07-31

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

1. whether differences in the methylation pattern of the promoters of dopaminergic genes exist between schizophrenic patients and healthy controls and

2. 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.

Conditions

Schizophrenia

Keywords

Schizophrenia; Dopamine transporter gene; DNA methylation; Epigenetics

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

A

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

Group Type: EXPERIMENTAL

Quetiapine fumarate

Intervention Type: DRUG

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

Interventions

Quetiapine fumarate

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

Intervention Type: DRUG

Other Intervention Names

Seroquel(R)

Eligibility Criteria

Inclusion Criteria

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

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)

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

University of Erlangen-Nürnberg Medical School

OTHER

Sponsor Role: lead

Responsible Party

University of Erlangen-Nürnberg

Principal Investigators

Stefan Bleich, MD

Role: PRINCIPAL_INVESTIGATOR

University of Erlangen-Nürnberg

Locations

Department of Psychiatry and Psychotherapy, University Erlangen-Nuremberg

Erlangen, , Germany

Countries

Germany

Other Identifiers

EudraCT-Nr: 2005-006151-20

Identifier Type: -

Identifier Source: secondary_id

D1449L00029

Identifier Type: -

Identifier Source: org_study_id