Clinical trial NCT00206960: 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
Overall status: COMPLETED
Phase: NA
Conditions: Schizophrenia
Keywords: drug-naive
epidepride
single tomography
D2 receptor
information processing
PPI
antipsychotic treatment
MRI
fMRI
cognitive disturbances
Lead sponsor: University of Copenhagen
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
name: Glostrup University Hospital, Copenhagen
name: Rigshospitalet, Denmark
name: Hvidovre University Hospital
name: The Danish Medical Research Council
name: Copenhagen Hospital Corporation
name: Janssen-Cilag Ltd.
name: The Novo Nordic Foundation
First posted: 2005-09-21
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: All examinations are done at baseline (patients and controls). In the patient group, they are repeated after 3 months of treatment
timeFrame: prospective
measure: PANSS
timeFrame: prospective
measure: SANS
timeFrame: prospective
measure: SAPS
timeFrame: prospective
measure: MRI
timeFrame: prospective
measure: fMRI
timeFrame: prospective
measure: startle response
timeFrame: prospective
measure: PrePulse Inhibition of the startle response (PPI)
timeFrame: prospective
measure: Cognition
timeFrame: prospective
Secondary outcomes:
measure: The cognitive test battery comprised tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) as well as paper-and-pencil cognitive tests.
timeFrame: prospective
Other outcomes:
Locations:
city: Copenhagen NV
country: Denmark
facility: Dept. of Nuclear Medicine, University of Copenhagen, Bispebjerg Hospital
city: Copenhagen NV
country: Denmark
facility: University of Copenhagen, Dept. F, Bispebjerg Hospital
city: Copenhagen NV
country: Denmark
facility: University of Copenhagen, Dept. of Psychiatry E, Bispebjerg Hospital
city: Copenhagen
country: Denmark
facility: Neurobiology Research Unit, University of Copenhagen, Rigshospitalet
city: Glostrup
country: Denmark
facility: Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen, Psychiatric Center Glostrup
city: Hvidovre
country: Denmark
facility: Danish Research Center for Magnetic Resonance Imaging, Hvidovre Hospital
Study officials:
affiliation: University of Copenhagen, Psychiatric Center Glostrup, Ndr. Ringvej, DK-2600 Glostrup, Denmark
name: Birte Glenthoj, MD, DMSc
role: STUDY_DIRECTOR
References:
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.
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.