Optimization of Treatment and Management of Schizophrenia in Europe (OPTIMISE): Substudy Site Copenhagen

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by University of Copenhagen
Sponsor:
Collaborators:
Glostrup University Hospital, Copenhagen
Rigshospitalet, Denmark
Institute of Psychiatry, London
UMC Utrecht
Copenhagen Hospital Corporation
Information provided by (Responsible Party):
Birte Glenthoj, University of Copenhagen
ClinicalTrials.gov Identifier:
NCT01555814
First received: September 19, 2011
Last updated: December 19, 2013
Last verified: December 2013
  Purpose

The investigators want to relate disturbances in first-episode schizophrenic patients in (dopaminergic) D2 receptors, brain structure, brain function, and information processing to each other and to psychopathology. Additionally, the investigators want to examine the influence of D2 receptor blockade on these disturbances. The investigators expect disturbances in the dopaminergic system at baseline to correlate with specific structural and functional changes and with disruption in information processing as measured with psychophysiological and neurocognitive methods - and investigators expect D2 receptor blockade to reverse some of the functional and cognitive impairments. The investigators do not expect any effect of treatment on brain structure.


Condition Intervention
Schizophrenia
Schizophreniform Disorder
Schizoaffective Disorder
Drug: Amisulpride

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Optimization of Treatment and Management of Schizophrenia in Europe (OPTIMISE): the Effects of D2 Antagonism on Candidate Endophenotypes

Resource links provided by NLM:


Further study details as provided by University of Copenhagen:

Primary Outcome Measures:
  • Relationship between specific neuropsychiatric measures and global improvement on PANSS scores [ Time Frame: 4 weeks of medical treatment ] [ Designated as safety issue: No ]
    Changes in neuropsychiatric measures like (e.g. PPI, P50-suppression, neurocogtion etc.) will be evaluated and related to the primary outcome measure of the main OPTiMiSE study, the PANSS score change from baseline to follow-up.


Secondary Outcome Measures:
  • Effect of antipsychotic medication on the D2 binding potential (SPECT) in antipsychotic naive patients with schizophrenia. [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]
    D2 receptor binding will be evaluated at baseline and after 4 weeks of treatment. This will be related to measures of the human reward system.

  • Effect of antipsychotic medication on P50-suppression [ Time Frame: Baseline, 4 weeks, 6,12,24 months ] [ Designated as safety issue: No ]
    Time/dose improvement on P50 suppression after antipsychotic treatment

  • Effect of antipsychotic medication on the human reward system [ Time Frame: Baseline and 4 weeks follow up ] [ Designated as safety issue: No ]
    Disturbances in the human reward system in antipsychotic naive patients with schizophrenia will be evaulated using a reward related BOLD fMRI paradigme.

  • Change in hippocampal and basal ganglia volume from baseline to follow-up. [ Time Frame: 4 weeks, 6, 12 and 24 months, ] [ Designated as safety issue: No ]
    Hippocampal volume decrease and basal ganglia volume increase is expected longitudinal outcomes.

  • Change in processing speed over time after antipsychotic treatment. [ Time Frame: Baseline, 4 weeks, 6,12,24 months ] [ Designated as safety issue: No ]
    Processing speed is expected to improve.

  • Change in levels of brain perfusion from baseline to follow-up. [ Time Frame: Baseline, 4 weeks treatment ] [ Designated as safety issue: No ]
    Brain perfusion levels will be measured in brain areas related to the human reward systems.


Estimated Enrollment: 180
Study Start Date: May 2011
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Amisulpride
For 4 weeks, all patients will be treated with amisulpride open label.
Drug: Amisulpride
4-week open label amisulpride treatment
Other Name: Solian

Detailed Description:

The study is designed as a 4 week case-control follow-up study of 90 FE pt. with SCZ and 90 controls matched with regard to age, gender, and parental socio-economic status. All subjects will be examined with a diagnostic interview (SCAN, Schedule for Clinical Assessment in Neuropsychiatry), medical and family history, and physical examination before inclusion. At baseline subjects will be examined with single photon emission computed tomography (SPECT), MRI, fMRI, psychophysiology, neurocognition. In addition, they will be screened for drugs, genetic testing, and ECG. Patients will further be examined with clinical validated rating scales to measure psychopathology, subjective well-being, and side-effects. After a period of 4 weeks all assessments are repeated. During that period patients will be treated with amisulpride, while healthy controls will receive no treatment at all. Efficacy of antipsychotic treatment will be evaluated after this initial period of 4 weeks. All subjects will be re-assessed in the same test battery as mentioned above, except for SPECT and fMRI, after a period of 6, 12, and 24 months.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Schizophrenia, schizophreniform or schizoaffective disorder (DSM-IV)
  • Age 18-40 years
  • Written informed consent.

Exclusion Criteria:

  • A time interval between the onset of positive symptoms (hallucinations and/or delusions) and study entry exceeding two years.
  • Prior use of antipsychotic medication longer than an episode of two weeks in the previous year and/or 6 weeks lifetime.
  • Intolerance to one of the drugs in this study. Patients who are coercively treated at a psychiatric ward (based on a judicial ruling)
  • Patients who are represented by a legal ward or under legal custody
  • The presence of one or more of the contraindications against any of the study drugs as mentioned in the SPC texts
  • Pregnancy, as determined through a pregnancy test, or lactation
  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: NCT01555814

Contacts
Contact: Birte Glenthøj, MD, DMSc +45 43 23 34 31 birte.glenthoj@cnsr.dk

Locations
Denmark
Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen, Psychiatric Center Glostrup Glostrup, Denmark Recruiting
Glostrup, Denmark
Contact: Brian Broberg, MSc, PhD    +45 386 40 834    brian@cnsr.dk   
Sub-Investigator: Signe Düring, MD         
Sub-Investigator: Brian Broberg, MSc, PhD         
Sub-Investigator: Sanne Wulff, MD         
Sub-Investigator: Bob Oranje, PhD         
Sub-Investigator: Birgitte Fagerlund, PhD         
Principal Investigator: Birte Glenthøj, MD, DMSc         
Sub-Investigator: Bjørn Ebdrup, MD, PhD         
Sponsors and Collaborators
Birte Glenthoj
Glostrup University Hospital, Copenhagen
Rigshospitalet, Denmark
Institute of Psychiatry, London
UMC Utrecht
Copenhagen Hospital Corporation
Investigators
Principal Investigator: Birte Glenthøj, MD, DMSc Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen, Psychiatric Center Glostrup Glostrup, Denmark
  More Information

Additional Information:
No publications provided

Responsible Party: Birte Glenthoj, Professor, University of Copenhagen
ClinicalTrials.gov Identifier: NCT01555814     History of Changes
Other Study ID Numbers: H-1-2010-142
Study First Received: September 19, 2011
Last Updated: December 19, 2013
Health Authority: Denmark: Danish Dataprotection Agency
Denmark: The Regional Committee on Biomedical Research Ethics

Keywords provided by University of Copenhagen:
dopamine
first episode
reward
cognition
MRI
fMRI
PPI
P300
P50 gating
endophenotypes

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

ClinicalTrials.gov processed this record on August 28, 2014