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

September 16, 2011 updated by: Birte Glenthoj

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

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.

Study Overview

Status

Completed

Conditions

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.

Study Type

Interventional

Enrollment (Actual)

56

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Copenhagen, Denmark, DK-2100
        • Neurobiology Research Unit, University of Copenhagen, Rigshospitalet
      • Copenhagen NV, Denmark, DK-2400
        • 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
      • Glostrup, Denmark, DK-2600
        • Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen, Psychiatric Center Glostrup
      • Hvidovre, Denmark, DK-2650
        • Danish Research Center for Magnetic Resonance Imaging, Hvidovre Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 2
Patients will be administered risperidone orally in doses between 1-6 mg/day, depending on an effective reduction of symptoms
Other Names:
  • Risperdal
Active Comparator: 1
Patients will be administered zuclopenthixol orally in doses between 4 -24 mg/day, depending on an effective reduction of symptoms
Other Names:
  • Cisordinol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
All examinations are done at baseline (patients and controls). In the patient group, they are repeated after 3 months of treatment
Time Frame: prospective
prospective
PANSS
Time Frame: prospective
prospective
SANS
Time Frame: prospective
prospective
SAPS
Time Frame: prospective
prospective
MRI
Time Frame: prospective
prospective
fMRI
Time Frame: prospective
prospective
startle response
Time Frame: prospective
prospective
PrePulse Inhibition of the startle response (PPI)
Time Frame: prospective
prospective
Cognition
Time Frame: prospective
prospective

Secondary Outcome Measures

Outcome Measure
Time Frame
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
prospective

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Study Director: Birte Glenthoj, MD, DMSc, University of Copenhagen, Psychiatric Center Glostrup, Ndr. Ringvej, DK-2600 Glostrup, Denmark

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 1998

Primary Completion (Actual)

September 1, 2010

Study Completion (Actual)

September 1, 2010

Study Registration Dates

First Submitted

September 10, 2005

First Submitted That Met QC Criteria

September 13, 2005

First Posted (Estimate)

September 21, 2005

Study Record Updates

Last Update Posted (Estimate)

September 19, 2011

Last Update Submitted That Met QC Criteria

September 16, 2011

Last Verified

September 1, 2011

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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