Official Title: “Quetiapine and the Dopaminergic Epigenetic Control - a Pilot Study”

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.

Study Type: Interventional

Study Design: Diagnostic, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: July 2008

Intervention(s) in this Clinical Trial

• Drug: Quetiapine fumarate
  • Dosage and frequency are judged by the study physician. The dosage must not excess 800mg/d.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A
  • There is only one arm in this study. All probands receive quetiapine.

Primary 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).
  • Time Frame: 6 month
    Safety Issue?: No

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

Exclusion criteria:

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

• 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)

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: University of Erlangen-Nürnberg Medical School

Overall Clinical Trial Officials and Contacts

Stefan Bleich, MD Principal Investigator University of Erlangen-Nürnberg Medical School  

Information obtained from ClinicalTrials.gov on March 10, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00370500

Study ID Number: D1449L00029

ClinicalTrials.gov Identifier: NCT00370500

Health Authority: Germany: Federal Institute for Drugs and Medical Devices

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