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

This study has been completed.
Sponsor:
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
Information provided by (Responsible Party):
Birte Glenthoj, University of Copenhagen
ClinicalTrials.gov Identifier:
NCT00206960
First received: September 10, 2005
Last updated: September 16, 2011
Last verified: September 2011
  Purpose

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.


Condition Intervention
Schizophrenia
Drug: zuclopenthixol
Drug: risperidone

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

Resource links provided by NLM:


Further study details as provided by University of Copenhagen:

Primary Outcome Measures:
  • All examinations are done at baseline (patients and controls). In the patient group, they are repeated after 3 months of treatment [ Time Frame: prospective ] [ Designated as safety issue: No ]
  • PANSS [ Time Frame: prospective ] [ Designated as safety issue: No ]
  • SANS [ Time Frame: prospective ] [ Designated as safety issue: No ]
  • SAPS [ Time Frame: prospective ] [ Designated as safety issue: No ]
  • MRI [ Time Frame: prospective ] [ Designated as safety issue: Yes ]
  • fMRI [ Time Frame: prospective ] [ Designated as safety issue: No ]
  • startle response [ Time Frame: prospective ] [ Designated as safety issue: No ]
  • PrePulse Inhibition of the startle response (PPI) [ Time Frame: prospective ] [ Designated as safety issue: No ]
  • Cognition [ Time Frame: prospective ] [ Designated as safety issue: No ]

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. [ Time Frame: prospective ] [ Designated as safety issue: No ]

Enrollment: 56
Study Start Date: January 1998
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1 Drug: zuclopenthixol
Patients will be administered zuclopenthixol orally in doses between 4 -24 mg/day, depending on an effective reduction of symptoms
Other Name: Cisordinol
Active Comparator: 2 Drug: risperidone
Patients will be administered risperidone orally in doses between 1-6 mg/day, depending on an effective reduction of symptoms
Other Name: Risperdal

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

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00206960

Locations
Denmark
Neurobiology Research Unit, University of Copenhagen, Rigshospitalet
Copenhagen, Denmark, DK-2100
Dept. of Nuclear Medicine, University of Copenhagen, Bispebjerg Hospital
Copenhagen NV, Denmark, DK-2400
University of Copenhagen, Dept. F, Bispebjerg Hospital
Copenhagen NV, Denmark, DK-2400
University of Copenhagen, Dept. of Psychiatry E, Bispebjerg Hospital
Copenhagen NV, Denmark, DK-2400
Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen, Psychiatric Center Glostrup
Glostrup, Denmark, DK-2600
Danish Research Center for Magnetic Resonance Imaging, Hvidovre Hospital
Hvidovre, Denmark, DK-2650
Sponsors and Collaborators
Birte Glenthoj
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
Investigators
Study Director: Birte Glenthoj, MD, DMSc University of Copenhagen, Psychiatric Center Glostrup, Ndr. Ringvej, DK-2600 Glostrup, Denmark
  More Information

Publications:
Responsible Party: Birte Glenthoj, Professor of Psychopharmacology and Neuropsychiatry, Danish Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen
ClinicalTrials.gov Identifier: NCT00206960     History of Changes
Other Study ID Numbers: 363002, KF 01-078/97, KF 01-012/98, KF 11-057/99
Study First Received: September 10, 2005
Last Updated: September 16, 2011
Health Authority: Denmark: National Board of Health

Keywords provided by University of Copenhagen:
drug-naive
epidepride
single tomography
D2 receptor
information processing
PPI
antipsychotic treatment
MRI
fMRI
cognitive disturbances

Additional relevant MeSH terms:
Schizophrenia
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Antipsychotic Agents
Clopenthixol
Risperidone
Central Nervous System Agents
Central Nervous System Depressants
Dopamine Agents
Dopamine Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Antagonists
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on October 23, 2014