Neurobiological and Neurocognitive Disturbances in First-episode Schizophrenia
Primary Purpose
Schizophrenia
Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
quetiapine
Sponsored by
About this trial
This is an interventional diagnostic trial for Schizophrenia focused on measuring first-episode, altanserin, 5-HT2A receptors, MRI, fMRI, PPI, P300, P50 gating, endophenotypes, vulnerability indicators, quetiapine
Eligibility 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
Sites / Locations
- Neurobiology Research Unit, Rigshospitalet
- Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen, Psychiatric Center Glostrup
- Danish Research Center for Magnetic Resonance Imaging, Hvidovre Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
Outcomes
Primary Outcome Measures
5-HT2A receptor binding and occupancy (PET)
Structural MRI
Functional MRI
Information procession as measured with psychophysiological methods (P300, PPI, P50 gating ect.)
An extensive battery of neurocognitive measures
Secondary Outcome Measures
PANSS
Full Information
NCT ID
NCT00207064
First Posted
September 10, 2005
Last Updated
September 16, 2011
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
1. Study Identification
Unique Protocol Identification Number
NCT00207064
Brief Title
Neurobiological and Neurocognitive Disturbances in First-episode Schizophrenia
Official Title
5-HT2A-receptor Binding: Implications for the Pathophysiology of Schizophrenia and Effects of Treatment With Antipsychotic Drugs
Study Type
Interventional
2. Study Status
Record Verification Date
September 2011
Overall Recruitment Status
Completed
Study Start Date
April 2004 (undefined)
Primary Completion Date
September 2008 (Actual)
Study Completion Date
September 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the 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
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
Keywords
first-episode, altanserin, 5-HT2A receptors, MRI, fMRI, PPI, P300, P50 gating, endophenotypes, vulnerability indicators, quetiapine
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
46 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
quetiapine
Intervention Description
flexible doses according to the clinical condition
Primary Outcome Measure Information:
Title
5-HT2A receptor binding and occupancy (PET)
Time Frame
Baseline and after 6 months
Title
Structural MRI
Time Frame
Baseline and after 6 months
Title
Functional MRI
Time Frame
Baseline and after 6 months
Title
Information procession as measured with psychophysiological methods (P300, PPI, P50 gating ect.)
Time Frame
Baseline and after 6 months
Title
An extensive battery of neurocognitive measures
Time Frame
Baseline and after 6 months
Secondary Outcome Measure Information:
Title
PANSS
Time Frame
Baseline and after 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Birte Glenthoj, MD, DMSc.
Organizational Affiliation
Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen, Psychaitric Center Glostrup, Ndr. Ringvej, DK-2600 Glostrup, Denmark
Official's Role
Study Director
Facility Information:
Facility Name
Neurobiology Research Unit, Rigshospitalet
City
Copenhagen
ZIP/Postal Code
DK-2100
Country
Denmark
Facility Name
Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen, Psychiatric Center Glostrup
City
Glostrup
ZIP/Postal Code
DK-2600
Country
Denmark
Facility Name
Danish Research Center for Magnetic Resonance Imaging, Hvidovre Hospital
City
Hvidovre
ZIP/Postal Code
DK-2650
Country
Denmark
12. IPD Sharing Statement
Citations:
PubMed Identifier
30420252
Citation
Jessen K, Mandl RCW, Fagerlund B, Bojesen KB, Raghava JM, Obaid HG, Jensen MB, Johansen LB, Nielsen MO, Pantelis C, Rostrup E, Glenthoj BY, Ebdrup BH. Patterns of Cortical Structures and Cognition in Antipsychotic-Naive Patients With First-Episode Schizophrenia: A Partial Least Squares Correlation Analysis. Biol Psychiatry Cogn Neurosci Neuroimaging. 2019 May;4(5):444-453. doi: 10.1016/j.bpsc.2018.09.006. Epub 2018 Sep 25.
Results Reference
derived
PubMed Identifier
20701823
Citation
Ebdrup BH, Skimminge A, Rasmussen H, Aggernaes B, Oranje B, Lublin H, Baare W, Glenthoj 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. doi: 10.1017/S1461145710000817. Epub 2010 Aug 12.
Results Reference
derived
PubMed Identifier
20184807
Citation
Ebdrup BH, Glenthoj B, Rasmussen H, Aggernaes B, Langkilde AR, Paulson OB, Lublin H, Skimminge A, Baare W. Hippocampal and caudate volume reductions in antipsychotic-naive first-episode schizophrenia. J Psychiatry Neurosci. 2010 Mar;35(2):95-104. doi: 10.1503/jpn.090049.
Results Reference
derived
PubMed Identifier
20048218
Citation
Rasmussen H, Erritzoe D, Andersen R, Ebdrup BH, Aggernaes B, Oranje B, Kalbitzer J, Madsen J, Pinborg LH, Baare 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. doi: 10.1001/archgenpsychiatry.2009.176.
Results Reference
derived
Links:
URL
http://www.cnsr.dk
Description
Center for Neuropsychiatric Schizophrenia Research (CNSR)
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Neurobiological and Neurocognitive Disturbances in First-episode Schizophrenia
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