Neurobiological and Neurocognitive Disturbances in First-episode Schizophrenia

Schizophrenia Clinical Trial

Official title:

5-HT2A-receptor Binding: Implications for the Pathophysiology of Schizophrenia and Effects of Treatment With Antipsychotic Drugs

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00207064
• Other study ID #: 363055
• Secondary ID: H-KF-01-078/97
• Status: Completed
• Phase: N/A
• First received: September 10, 2005
• Last updated: September 16, 2011
• Start date: April 2004
• Est. completion date: September 2008

Study information

• Verified date: September 2011
• Source: University of Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: National Board of Health
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: September 2008
• Est. primary completion date: September 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• quetiapine
flexible doses according to the clinical condition

Locations

Country	Name	City	State
Denmark	Neurobiology Research Unit, Rigshospitalet	Copenhagen
Denmark	Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen, Psychiatric Center Glostrup	Glostrup
Denmark	Danish Research Center for Magnetic Resonance Imaging, Hvidovre Hospital	Hvidovre

Sponsors (8)

Lead Sponsor	Collaborator
Birte Glenthoj	AstraZeneca, Copenhagen Hospital Corporation, Copenhagen University Hospital, Hvidovre, Glostrup University Hospital, Copenhagen, Rigshospitalet, Denmark, The Danish Medical Research Council, University of Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	5-HT2A receptor binding and occupancy (PET)		Baseline and after 6 months	No
Primary	Structural MRI		Baseline and after 6 months	No
Primary	Functional MRI		Baseline and after 6 months	No
Primary	Information procession as measured with psychophysiological methods (P300, PPI, P50 gating ect.)		Baseline and after 6 months	No
Primary	An extensive battery of neurocognitive measures		Baseline and after 6 months	No
Secondary	PANSS		Baseline and after 6 months	No

External Links

•   Center for Neuropsychiatric Schizophrenia Research (CNSR)