Dopaminergic, Functional, Structural, and Cognitive Disturbances in First-episode Schizophrenia
Primary Purpose
Schizophrenia
Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
zuclopenthixol
risperidone
Sponsored by
About this trial
This is an interventional diagnostic trial for Schizophrenia focused on measuring drug-naive, epidepride, single tomography, D2 receptor, information processing, PPI, antipsychotic treatment, MRI, fMRI, cognitive disturbances
Eligibility Criteria
Inclusion Criteria: For patients: Clinical diagnosis of schizophrenia. The controls were matched to the patients. Exclusion Criteria: Patients: Previous antipsychotic treatment, patients who were compulsorily hospitalised or deemed in acute need of medication, mental retardation Controls: psychiatric diagnosis, psychiatric diagnosis in first-degree relatives, drug abuse, mental retardation
Sites / Locations
- Dept. of Nuclear Medicine, University of Copenhagen, Bispebjerg Hospital
- University of Copenhagen, Dept. F, Bispebjerg Hospital
- University of Copenhagen, Dept. of Psychiatry E, Bispebjerg Hospital
- Neurobiology Research Unit, University of Copenhagen, 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 2
Arm Type
Active Comparator
Active Comparator
Arm Label
1
2
Arm Description
Outcomes
Primary Outcome Measures
All examinations are done at baseline (patients and controls). In the patient group, they are repeated after 3 months of treatment
PANSS
SANS
SAPS
MRI
fMRI
startle response
PrePulse Inhibition of the startle response (PPI)
Cognition
Secondary Outcome Measures
The cognitive test battery comprised tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) as well as paper-and-pencil cognitive tests.
Full Information
NCT ID
NCT00206960
First Posted
September 10, 2005
Last Updated
September 16, 2011
Sponsor
Birte Glenthoj
Collaborators
University of Copenhagen, Glostrup University Hospital, Copenhagen, Rigshospitalet, Denmark, Hvidovre University Hospital, The Danish Medical Research Council, Copenhagen Hospital Corporation, Janssen-Cilag Ltd., The Novo Nordic Foundation
1. Study Identification
Unique Protocol Identification Number
NCT00206960
Brief Title
Dopaminergic, Functional, Structural, and Cognitive Disturbances in First-episode Schizophrenia
Official Title
Effects of Classical and Atypical Antipsychotics on Dopamine Receptor Binding of 123I-epidepride, Cognition, Startle Response and Extrapyramidal Side-effects in Drug-naive First-episode Schizophrenic Patients
Study Type
Interventional
2. Study Status
Record Verification Date
September 2011
Overall Recruitment Status
Completed
Study Start Date
January 1998 (undefined)
Primary Completion Date
September 2010 (Actual)
Study Completion Date
September 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Birte Glenthoj
Collaborators
University of Copenhagen, Glostrup University Hospital, Copenhagen, Rigshospitalet, Denmark, Hvidovre University Hospital, The Danish Medical Research Council, Copenhagen Hospital Corporation, Janssen-Cilag Ltd., The Novo Nordic Foundation
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
We wanted to compare dopamine D2 receptor activity, brain structure, brain function, sensory gating and cognition in neuroleptic-naive schizophrenic patients and matched healthy controls. Additionally, we wanted to examine the effects of 3 months of treatment with either low doses of a typical or an atypical antipsychotic compound on the same functions. The hypotheses were that schizophrenic patients suffered from disturbances in brain function and structure, information processing, and extrastriatal D2 receptor activity, and that these disturbances would be related to each other and to psychopathology. Additionally, we expected the atypical compound to have an effect on some of the disturbances in information processing, and that the atypical compound - in contrast to the typical drug - would show extrastriatal over striatal selectivity.
Detailed Description
31 neuroleptic-naive schizophrenic patients and 25 matched controls were recruited from the greater Copenhagen area. The patients were randomized to treatment with either low doses of the typical antipsychotic compound, zuclopenthixol, or the atypical drug, risperidone. Patients and controls were examined at base-line and patients were re-examined after 3 months of treatment.The study has resulted in two finish Ph.D. theses (Torben Mackeprang and Birgitte Fagerlund).
The data has in part been published in:
Mackeprang T, Tjelle Kristiansen K, Glenthoj B. Prepulse inhibition of the startle response in drug-naïve, first-episode schizophrenic patients before and after 3 months of treatment with a typical or an atypical antipsychotic drug. Biological Psychiatry 2002; 52(9): 863-873.
and
Fagerlund B, Mackeprang T, Gade A, Hemmingsen R, Glenthoj BY. Effects of Low-Dose Risperidone and Low-Dose Zuclopenthixol on Cognitive Functions in First-Episode Drug-Naïve Schizophrenic Patients. CNS Spectr. 2004; 9: 364-74.
and
Glenthoj BY, Mackeprang T, Svarer C, Rasmussen H, Pinborg L, Friberg L, Baaré W, Hemmingsen R, Videbæk C. Frontal dopamine D2/3 receptor binding in drug-naïve first-episode schizophrenic patients correlates with positive psychotic symptoms and gender. Biological Psychiatry 2006; in press. Mar 30; [Epub ahead of print]. PMID: 16784819 [PubMed - as supplied by publisher].
We are at present conducting a five-year follow-up study of the same cohort of patients and controls and plan a ten-year follow-up as well. The follow-up studies focus on brain structure (MRI), brain function, information processing, and psychopathology. We will correlate changes in structure and function to treatment, but no interventions (pharmacological or otherwise) are planned.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
Keywords
drug-naive, epidepride, single tomography, D2 receptor, information processing, PPI, antipsychotic treatment, MRI, fMRI, cognitive disturbances
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
56 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Active Comparator
Arm Title
2
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
zuclopenthixol
Other Intervention Name(s)
Cisordinol
Intervention Description
Patients will be administered zuclopenthixol orally in doses between 4 -24 mg/day, depending on an effective reduction of symptoms
Intervention Type
Drug
Intervention Name(s)
risperidone
Other Intervention Name(s)
Risperdal
Intervention Description
Patients will be administered risperidone orally in doses between 1-6 mg/day, depending on an effective reduction of symptoms
Primary Outcome Measure Information:
Title
All examinations are done at baseline (patients and controls). In the patient group, they are repeated after 3 months of treatment
Time Frame
prospective
Title
PANSS
Time Frame
prospective
Title
SANS
Time Frame
prospective
Title
SAPS
Time Frame
prospective
Title
MRI
Time Frame
prospective
Title
fMRI
Time Frame
prospective
Title
startle response
Time Frame
prospective
Title
PrePulse Inhibition of the startle response (PPI)
Time Frame
prospective
Title
Cognition
Time Frame
prospective
Secondary Outcome Measure Information:
Title
The cognitive test battery comprised tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) as well as paper-and-pencil cognitive tests.
Time Frame
prospective
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:
For patients: Clinical diagnosis of schizophrenia.
The controls were matched to the patients.
Exclusion Criteria:
Patients: Previous antipsychotic treatment, patients who were compulsorily hospitalised or deemed in acute need of medication, mental retardation
Controls: psychiatric diagnosis, psychiatric diagnosis in first-degree relatives, drug abuse, mental retardation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Birte Glenthoj, MD, DMSc
Organizational Affiliation
University of Copenhagen, Psychiatric Center Glostrup, Ndr. Ringvej, DK-2600 Glostrup, Denmark
Official's Role
Study Director
Facility Information:
Facility Name
Dept. of Nuclear Medicine, University of Copenhagen, Bispebjerg Hospital
City
Copenhagen NV
ZIP/Postal Code
DK-2400
Country
Denmark
Facility Name
University of Copenhagen, Dept. F, Bispebjerg Hospital
City
Copenhagen NV
ZIP/Postal Code
DK-2400
Country
Denmark
Facility Name
University of Copenhagen, Dept. of Psychiatry E, Bispebjerg Hospital
City
Copenhagen NV
ZIP/Postal Code
DK-2400
Country
Denmark
Facility Name
Neurobiology Research Unit, University of Copenhagen, 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
12399139
Citation
Mackeprang T, Kristiansen KT, Glenthoj BY. Effects of antipsychotics on prepulse inhibition of the startle response in drug-naive schizophrenic patients. Biol Psychiatry. 2002 Nov 1;52(9):863-73. doi: 10.1016/s0006-3223(02)01409-9.
Results Reference
result
PubMed Identifier
15115949
Citation
Fagerlund B, Mackeprang T, Gade A, Glenthoj BY. Effects of low-dose risperidone and low-dose zuclopenthixol on cognitive functions in first-episode drug-naive schizophrenic patients. CNS Spectr. 2004 May;9(5):364-74. doi: 10.1017/s1092852900009354.
Results Reference
result
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Dopaminergic, Functional, Structural, and Cognitive Disturbances in First-episode Schizophrenia
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