Dopaminergic, Functional, Structural, and Cognitive Disturbances in First-episode Schizophrenia

Schizophrenia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00206960
• Other study ID #: 363002
• Secondary ID: KF 01-078/97KF 0
• Status: Completed
• Phase: N/A
• First received: September 10, 2005
• Last updated: September 16, 2011
• Start date: January 1998
• Est. completion date: September 2010

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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: September 2010
• Est. primary completion date: September 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• zuclopenthixol
Patients will be administered zuclopenthixol orally in doses between 4 -24 mg/day, depending on an effective reduction of symptoms
• risperidone
Patients will be administered risperidone orally in doses between 1-6 mg/day, depending on an effective reduction of symptoms

Locations

Country	Name	City	State
Denmark	Neurobiology Research Unit, University of Copenhagen, Rigshospitalet	Copenhagen
Denmark	Dept. of Nuclear Medicine, University of Copenhagen, Bispebjerg Hospital	Copenhagen NV
Denmark	University of Copenhagen, Dept. F, Bispebjerg Hospital	Copenhagen NV
Denmark	University of Copenhagen, Dept. of Psychiatry E, Bispebjerg Hospital	Copenhagen NV
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 (9)

Lead Sponsor	Collaborator
Birte Glenthoj	Copenhagen Hospital Corporation, Glostrup University Hospital, Copenhagen, Hvidovre University Hospital, Janssen-Cilag Ltd., Rigshospitalet, Denmark, The Danish Medical Research Council, The Novo Nordic Foundation, University of Copenhagen

Country where clinical trial is conducted

Denmark, 

References & Publications (2)

Fagerlund B, Mackeprang T, Gade A, Glenthøj 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. — View Citation

Mackeprang T, Kristiansen KT, Glenthoj BY. Effects of antipsychotics on prepulse inhibition of the startle response in drug-naïve schizophrenic patients. Biol Psychiatry. 2002 Nov 1;52(9):863-73. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All examinations are done at baseline (patients and controls). In the patient group, they are repeated after 3 months of treatment		prospective	No
Primary	PANSS		prospective	No
Primary	SANS		prospective	No
Primary	SAPS		prospective	No
Primary	MRI		prospective	Yes
Primary	fMRI		prospective	No
Primary	startle response		prospective	No
Primary	PrePulse Inhibition of the startle response (PPI)		prospective	No
Primary	Cognition		prospective	No
Secondary	The cognitive test battery comprised tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) as well as paper-and-pencil cognitive tests.		prospective	No