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

NCT ID: NCT00206960

Last Updated: 2011-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1998-01-31
• Study Completion Date: 2010-09-30

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.

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

1

Group Type: ACTIVE_COMPARATOR

zuclopenthixol

Intervention Type: DRUG

Patients will be administered zuclopenthixol orally in doses between 4 -24 mg/day, depending on an effective reduction of symptoms

2

Group Type: ACTIVE_COMPARATOR

risperidone

Intervention Type: DRUG

Patients will be administered risperidone orally in doses between 1-6 mg/day, depending on an effective reduction of symptoms

Interventions

zuclopenthixol

Patients will be administered zuclopenthixol orally in doses between 4 -24 mg/day, depending on an effective reduction of symptoms

Intervention Type: DRUG

risperidone

Patients will be administered risperidone orally in doses between 1-6 mg/day, depending on an effective reduction of symptoms

Intervention Type: DRUG

Other Intervention Names

Cisordinol; Risperdal

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Copenhagen

OTHER

Sponsor Role: collaborator

Glostrup University Hospital, Copenhagen

OTHER

Sponsor Role: collaborator

Rigshospitalet, Denmark

OTHER

Sponsor Role: collaborator

Hvidovre University Hospital

OTHER

Sponsor Role: collaborator

The Danish Medical Research Council

OTHER

Sponsor Role: collaborator

Copenhagen Hospital Corporation

OTHER

Sponsor Role: collaborator

Janssen-Cilag Ltd.

INDUSTRY

Sponsor Role: collaborator

The Novo Nordic Foundation

OTHER

Sponsor Role: collaborator

Birte Glenthoj

OTHER

Sponsor Role: lead

Responsible Party

Birte Glenthoj

Professor of Psychopharmacology and Neuropsychiatry, Danish Center for Neuropsychiatric Schizophrenia Research

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Birte Glenthoj, MD, DMSc

Role: STUDY_DIRECTOR

University of Copenhagen, Psychiatric Center Glostrup, Ndr. Ringvej, DK-2600 Glostrup, Denmark

Locations

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 Municipality, , Denmark

Danish Research Center for Magnetic Resonance Imaging, Hvidovre Hospital

Hvidovre, , Denmark

Countries

Denmark

References

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.

Reference Type: RESULT

PMID: 12399139 (View on PubMed)

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.

Reference Type: RESULT

PMID: 15115949 (View on PubMed)

Other Identifiers

KF 01-078/97

Identifier Type: -

Identifier Source: secondary_id

KF 01-012/98

Identifier Type: -

Identifier Source: secondary_id

KF 11-057/99

Identifier Type: -

Identifier Source: secondary_id

363002

Identifier Type: -

Identifier Source: org_study_id