Full Text View
Tabular View
No Study Results Posted
Related Studies
Quetiapine and the Dopaminergic Epigenetic Control
This study has been completed.
First Received: August 30, 2006   Last Updated: July 9, 2008   History of Changes
Sponsors and Collaborators: University of Erlangen-Nürnberg
AstraZeneca
Information provided by: University of Erlangen-Nürnberg
ClinicalTrials.gov Identifier: NCT00370500
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Drug: Quetiapine fumarate
Phase IV

MedlinePlus related topics: Schizophrenia
Drug Information available for: Dopamine Dopamine hydrochloride Quetiapine Quetiapine fumarate
U.S. FDA Resources
Study Type: Interventional
Study Design: Diagnostic, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title: Quetiapine and the Dopaminergic Epigenetic Control - a Pilot Study

Further study details as provided by University of Erlangen-Nürnberg:

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). [ Time Frame: 6 month ] [ Designated as safety issue: No ]

Enrollment: 100
Study Start Date: April 2007
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
A: Experimental
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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00370500

Locations
Germany
Department of Psychiatry and Psychotherapy, University Erlangen-Nuremberg
Erlangen, Germany, 91054
Sponsors and Collaborators
University of Erlangen-Nürnberg
AstraZeneca
Investigators
Principal Investigator: Stefan Bleich, MD University of Erlangen-Nuremberg
  More Information

Additional Information:
No publications provided

Responsible Party: University of Erlangen-Nürnberg ( Stefan Bleich )
Study ID Numbers: D1449L00029, EudraCT-Nr: 2005-006151-20
Study First Received: August 30, 2006
Last Updated: July 9, 2008
ClinicalTrials.gov Identifier: NCT00370500     History of Changes
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University of Erlangen-Nürnberg:
Schizophrenia
Dopamine transporter gene
DNA methylation
Epigenetics

Study placed in the following topic categories:
Neurotransmitter Agents
Tranquilizing Agents
Psychotropic Drugs
Central Nervous System Depressants
Dopamine Agonists
Antipsychotic Agents
Schizophrenia
Quetiapine
Dopamine
Mental Disorders
Psychotic Disorders
Dopamine Agents
Schizophrenia and Disorders with Psychotic Features

Additional relevant MeSH terms:
Neurotransmitter Agents
Tranquilizing Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Psychotropic Drugs
Central Nervous System Depressants
Dopamine Agonists
Antipsychotic Agents
Pharmacologic Actions
Schizophrenia
Quetiapine
Mental Disorders
Therapeutic Uses
Dopamine Agents
Central Nervous System Agents
Schizophrenia and Disorders with Psychotic Features

ClinicalTrials.gov processed this record on May 07, 2009