Neurobiological and Neurocognitive Disturbances in First-episode Schizophrenia - Full Text View

Sponsor:	Birte Glenthoj
Collaborators:	Rigshospitalet, Denmark Copenhagen University Hospital, Hvidovre Glostrup University Hospital, Copenhagen The Danish Medical Research Council Copenhagen Hospital Corporation University of Copenhagen AstraZeneca
Information provided by (Responsible Party):	Birte Glenthoj, University of Copenhagen
ClinicalTrials.gov Identifier:	NCT00207064

Purpose

We want to relate disturbances in first-episode schizophrenic patients in serotonin 5-HT2A receptors, brain structure, brain function, and information processing to each other and to psychopathology. Additionally, we want to examine the influence of 5-HT2A receptor blockade on these disturbances. We expect disturbances in the serotonergic system at baseline to correlate with specific structural and functional changes and with disruption in information processing as measured with psychophysiological and neurocognitive methods - and we expect 5-HT2A receptor blockade to reverse some of the functional and cognitive impairments. We do not expect any effect of treatment on brain structure

Condition	Intervention
Schizophrenia	Drug: quetiapine

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Factorial Assignment Masking: Open Label Primary Purpose: Diagnostic
Official Title:	5-HT2A-receptor Binding: Implications for the Pathophysiology of Schizophrenia and Effects of Treatment With Antipsychotic Drugs

Resource links provided by NLM:

MedlinePlus related topics: Schizophrenia

Drug Information available for: Quetiapine Quetiapine fumarate

U.S. FDA Resources

Further study details as provided by University of Copenhagen:

Primary Outcome Measures:

5-HT2A receptor binding and occupancy (PET) [ Time Frame: Baseline and after 6 months ] [ Designated as safety issue: No ]
Structural MRI [ Time Frame: Baseline and after 6 months ] [ Designated as safety issue: No ]
Functional MRI [ Time Frame: Baseline and after 6 months ] [ Designated as safety issue: No ]
Information procession as measured with psychophysiological methods (P300, PPI, P50 gating ect.) [ Time Frame: Baseline and after 6 months ] [ Designated as safety issue: No ]
An extensive battery of neurocognitive measures [ Time Frame: Baseline and after 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

PANSS [ Time Frame: Baseline and after 6 months ] [ Designated as safety issue: No ]

Enrollment:	46
Study Start Date:	April 2004
Study Completion Date:	September 2008
Primary Completion Date:	September 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1	Drug: quetiapine flexible doses according to the clinical condition

Detailed Description:

Patients and matched healthy controls are examined at baseline and again after the patients have been treated for 6 months with a combined 5-HT2A- and dopamine D2- receptor blocker. We have chosen the atypical antipsychotic compound, quetiapine, for the present study since this drug is characterized by a fast koff/low affinity for the dopamine D2 receptors. The purpose of the study is to examine pathophysiological and neuropsychological mechanisms - not treatment effects. We want to characterize neurobiological and functional endophenotypes or vulnerability indicators and to study their stability over time and their relation to treatment and contemporary psychopathology. To the extent that candidate endophenotypes can be characterized as stable and independent of treatment and contemporary psychopathology they will be analysed together with similar findings from previous (identical)cohorts of schizophrenic patients. Specific disturbances will also be related to candidate genes for schizophrenia.

Eligibility

Ages Eligible for Study:	18 Years to 45 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

First-episode schizophrenia. The controls are matched for age, gender and parental socioeconomic status

Exclusion Criteria:

Previous antipsychotic treatment, mental retardation, organic brain damage, and for the controls a psychiatric diagnosis or first-degree relatives with a psychiatric diagnosis

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00207064

Locations

Denmark
Neurobiology Research Unit, Rigshospitalet
Copenhagen, Denmark, DK-2100
Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen, Psychiatric Center Glostrup
Glostrup, Denmark, DK-2600
Danish Research Center for Magnetic Resonance Imaging, Hvidovre Hospital
Hvidovre, Denmark, DK-2650

Sponsors and Collaborators

Birte Glenthoj

Rigshospitalet, Denmark

Copenhagen University Hospital, Hvidovre

Glostrup University Hospital, Copenhagen

The Danish Medical Research Council

Copenhagen Hospital Corporation

University of Copenhagen

AstraZeneca

Investigators

Study Director:

Birte Glenthoj, MD, DMSc.

Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen, Psychaitric Center Glostrup, Ndr. Ringvej, DK-2600 Glostrup, Denmark

More Information

Additional Information:

Center for Neuropsychiatric Schizophrenia Research (CNSR) This link exits the ClinicalTrials.gov site

No publications provided by University of Copenhagen

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ebdrup BH, Skimminge A, Rasmussen H, Aggernaes B, Oranje B, Lublin H, Baaré W, Glenthøj B. Progressive striatal and hippocampal volume loss in initially antipsychotic-naive, first-episode schizophrenia patients treated with quetiapine: relationship to dose and symptoms. Int J Neuropsychopharmacol. 2011 Feb;14(1):69-82. Epub 2010 Aug 12.

Ebdrup BH, Glenthøj B, Rasmussen H, Aggernaes B, Langkilde AR, Paulson OB, Lublin H, Skimminge A, Baaré W. Hippocampal and caudate volume reductions in antipsychotic-naive first-episode schizophrenia. J Psychiatry Neurosci. 2010 Mar;35(2):95-104.

Rasmussen H, Erritzoe D, Andersen R, Ebdrup BH, Aggernaes B, Oranje B, Kalbitzer J, Madsen J, Pinborg LH, Baaré W, Svarer C, Lublin H, Knudsen GM, Glenthoj B. Decreased frontal serotonin2A receptor binding in antipsychotic-naive patients with first-episode schizophrenia. Arch Gen Psychiatry. 2010 Jan;67(1):9-16.

Responsible Party:	Birte Glenthoj, Professor of Psychopharmacology and Neuropsychiatry, Danish Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen
ClinicalTrials.gov Identifier:	NCT00207064 History of Changes
Other Study ID Numbers:	363055, H-KF-01-078/97
Study First Received:	September 10, 2005
Last Updated:	September 16, 2011
Health Authority:	Denmark: National Board of Health

Keywords provided by University of Copenhagen:

first-episode
altanserin
5-HT2A receptors
MRI
fMRI
PPI

P300
P50 gating
endophenotypes
vulnerability indicators
quetiapine

Additional relevant MeSH terms:

Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Antipsychotic Agents
Quetiapine
Tranquilizing Agents

Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs

ClinicalTrials.gov processed this record on February 09, 2012