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Quetiapine and the Dopaminergic Epigenetic Control

This study has been completed.
Sponsor:
Collaborator:
AstraZeneca
Information provided by:
University of Erlangen-Nürnberg Medical School
ClinicalTrials.gov Identifier:
NCT00370500
First received: August 30, 2006
Last updated: July 9, 2008
Last verified: July 2008
  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 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Quetiapine and the Dopaminergic Epigenetic Control - a Pilot Study

Resource links provided by NLM:


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

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
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 Name: Seroquel(R)

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

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

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

ClinicalTrials.gov processed this record on November 24, 2014